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Background : In the era of advanced surgical techniques and improved perioperative care , the willingness to perform emergency operations in elderly patients continues to increase . This systematic review aim ed at assessing the clinical outcomes of early cholecystectomy in elderly patients with acute cholecystitis . Methods : Medline , Embase , and Cochrane Library data bases were systematic ally search ed for studies reporting on early cholecystectomy for acute cholecystitis in patients aged ≥70 years . The conversion rate , perioperative morbidity , and mortality were calculated using a r and om-effects model . Results : Eight articles fell within the scope of this study . In total , 592 patients were identified . The mean age was 81 years . Early cholecystectomy was performed laparoscopically in 316 patients ( 53 % ) and open in 276 patients ( 47 % ) . The procedure was associated with a conversion rate of 23 % ( 95 % CI 18.6 - 28.3 ) , a perioperative morbidity of 24 % ( 95 % CI 20.5 - 27.5 ) , and a mortality of 3.5 % ( 95 % CI 2.3 - 5.4 ) . Conclusion : Early cholecystectomy seems to be a feasible treatment in elderly patients with acute cholecystitis . To reduce morbidity , patients who may benefit from surgery ought to be selected carefully . Future prospect i ve studies should compare early cholecystectomy with alternative treatments to select the treatment that is most appropriate for elderly patients	[ "Background The aim if this study was to compare percutaneous drainage ( PD ) of the gallbladder to emergency cholecystectomy ( EC ) in a well-defined patient group with sepsis related to acute calculous/acalculous cholecystitis ( ACC/AAC ) . Methods Between 2001 and 2007 , all consecutive patients of our ICU treated by either PD or EC were retrospectively analyzed . Cases were collected from a prospect i ve data base . Percutaneous drainage was performed by a transhepatic route and EC by open or laparoscopic approach . Patients ’ general condition and organ dysfunction were assessed by two vali date d scoring systems ( SAPS II and SOFA , respectively ) . Morbidity , mortality , and long-term outcome were systematic ally review ed and analyzed in both groups . Results Forty-two patients [ median age = 65.5 years ( range = 32–94 ) ] were included ; 45 % underwent EC ( ten laparoscopic , nine open ) and 55 % PD ( n = 23 ) . Both patient groups had similar preoperative characteristics . Percutaneous drainage and EC were successful in 91 and 100 % of patients , respectively . Organ dysfunctions were similarly improved by the third postoperative/postdrainage days . Despite undergoing PD , two patients required EC due to gangrenous cholecystitis . The conversion rate after laparoscopy was 20 % . Overall morbidity was 8.7 % after PD and 47 % after EC ( P = 0.011 ) . Major morbidity was 0 % after PD and 21 % after EC ( P = 0.034 ) . The mortality rate was not different ( 13 % after PD and 16 % after EC , P = 1.0 ) and the deaths were all related to the patients ’ preexisting disease . Hospital and ICU stays were not different . Recurrent symptoms ( 17 % ) occurred only after ACC in the PD group . Conclusions In high-risk patients , PD and EC are both efficient in the resolution of acute cholecystitis sepsis . However , EC is associated with a higher procedure-related morbidity and the laparoscopic approach is not always possible . Percutaneous drainage represents a valuable intervention , but secondary cholecystectomy is m and atory in cases of acute calculous cholecystitis", "The aim of this prospect i ve comparative study was to determine the feasibility and the efficacy of laparoscopic cholecystectomy for acute cholecystitis in patients older than 75 years of age and to compare the results with those of open cholecystectomy . From January 1992 to December 1999 , 139 patients older than 75 years of age underwent cholecystectomy for acute cholecystitis . The two groups of patients with cholecystolithiasis included 50 patients who underwent laparoscopic cholecystectomy ( group 1 ) and 89 patients who underwent open cholecystectomy ( group 2 ) . Group 1 consisted of 30 women and 20 men , with a mean age of 81.9 years ( range , 75–98 ) . Group 2 consisted of 51 women and 38 men , with a mean age of 81.9 years ( range , 75–93 ) . There was no difference in the American Society of Anesthesiologists classification in both groups . The length of the surgery ( 103.3 vs. 149.7 minutes ) , postoperative length of stay ( 7.7 vs. 12.7 days ) , and inpatient rehabilitation ( 15 vs. 42 patients ) were significantly shorter in group 1 than in group 2 . The postoperative morbidity rate was not different between the groups . There was no mortality in group 1 , but four patients died in group 2 ( P = 0.29 ) . The conversion rate was 32 % ( n = 16 ) in group 1 . In summary , laparoscopic cholecystectomy in elderly patients with acute cholecystitis is safe and effective . Laparoscopic cholecystectomy in elderly patients restores them to the best possible quality of life with the lowest cost to them physiologically", "Background : The role of laparoscopic cholecystectomy for acute cholecystitis is not yet clearly established . The aim of this prospect i ve r and omized study was to evaluate the safety and feasibility of laparoscopic cholecystectomy for acute cholecystitis and to compare the results with delayed cholecystectomy . Methods : Between January 2001 and November 2002 , 40 patients with a diagnosis of acute cholecystitis were assigned r and omly to early laparoscopic cholecystectomy within 24 h of admission ( early group , n = 20 ) or to initial conservative treatment followed by delayed laparoscopic cholecystectomy , 6 to 12 weeks later ( delayed group , n = 20 ) . Results : There was no significant difference in the conversion rates ( early , 25 % vs delayed , 25 % ) , operating times ( early , 104 min vs delayed , 93 min ) , postoperative analgesia requirements ( early , 5.3 days vs delayed , 4.8 days ) , or postoperative complications ( early , 15 % vs delayed , 20 % ) . However , the early group had significantly more blood loss ( 228 vs 114 ml ) and shorter hospital stay ( 4.1 vs 10.1 days ) . Conclusions : Early laparoscopic cholecystectomy for acute cholecystitis is safe and feasible , offering the additional benefit of a shorter hospital stay . It should be offered to patients with acute cholecystitis , provided the surgery is performed within 72 to 96 h of the onset of symptoms", "Background Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality . Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice . Methods / Design The CHOCOLATE trial is a r and omised controlled , parallel-group , superiority multicenter trial . High risk patients , defined as APACHE-II score 7 - 14 , with acute calculous cholecystitis will be r and omised to laparoscopic cholecystectomy or percutaneous cholecystostomy . During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals . The primary endpoint is a composite endpoint of major complications within three months following r and omization and need for re-intervention and mortality during the follow-up period of one year . Secondary endpoints include all other complications , duration of hospital admission , difficulty of procedures and total costs . Discussion The CHOCOLATE trial is design ed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients .Trial Registration Netherl and s Trial Register ( NTR ) :", "OBJECTIVES Percutaneous cholecystostomy ( PC ) is an established low-mortality treatment option for elderly and critically ill patients with acute cholecystitis . The primary aim of this review is to find out if there is any evidence in the literature to recommend PC rather than cholecystectomy for acute cholecystitis in the elderly population . METHODS In April 2007 , a systematic electronic data base search was performed on the subject of PC and cholecystectomy in the elderly population . After exclusions , 53 studies remained , comprising 1918 patients . Three papers described r and omized controlled trials ( RCTs ) , but none compared the outcomes of PC and cholecystectomy . A total of 19 papers on mortality after cholecystectomy in patients aged > 65 years were identified . RESULTS Successful intervention was seen in 85.6 % of patients with acute cholecystitis . A total of 40 % of patients treated with PC were later cholecystectomized , with a mortality rate of 1.96 % . Procedure mortality was 0.36 % , but 30-day mortality rates were 15.4 % in patients treated with PC and 4.5 % in those treated with acute cholecystectomy ( P PC vs. cholecystectomy and the papers review ed are of evidence grade C. It is not possible to make definitive recommendations regarding treatment by PC or cholecystectomy in elderly or critically ill patients with acute cholecystitis . Low mortality rates after cholecystectomy in elderly patients with acute cholecystitis have been reported in recent years and therefore we believe it is time to launch an RCT to address this issue", "Objective : Acute cholecystitis is a common disease , and laparoscopic surgery is the st and ard of care . Background : Optimal timing of surgery for acute cholecystitis remains controversial : either early surgery shortly after hospital admission or delayed elective surgery after a conservative treatment with antibiotics . Methods : The ACDC ( “ Acute Cholecystitis — early laparoscopic surgery versus antibiotic therapy and Delayed elective Cholecystectomy ” ) study is a r and omized , prospect i ve , open-label , parallel group trial . Patients were r and omly assigned to receive immediate surgery within 24 hours of hospital admission ( group ILC ) or initial antibiotic treatment , followed by delayed laparoscopic cholecystectomy at days 7 to 45 ( group DLC ) . For infection , all patients were treated with moxifloxacin for at least 48 hours . Primary endpoint was occurrence of predefined relevant morbidity within 75 days . Secondary endpoints were as follows : ( 1 ) 75-day morbidity using a scoring system ; ( 2 ) conversion rate ; ( 3 ) change of antibiotic therapy ; ( 4 ) mortality ; ( 5 ) costs ; and ( 6 ) length of hospital stay . Results : Morbidity rate was significantly lower in group ILC ( 304 patients ) than in group DLC ( 314 patients ): 11.8 % versus 34.4 % . Conversion rate to open surgery and mortality did not differ significantly between groups . Mean length of hospital stay ( 5.4 days vs 10.0 days ; P total hospital costs ( & OV0556;2919 vs & OV0556;4262 ; P morbidity and costs . Therefore , we believe that immediate laparoscopic cholecystectomy should become therapy of choice for acute cholecystitis in operable patients . ( NCT00447304", "Abstract . Our objective was to compare the effectiveness of percutaneous cholecystostomy ( PC ) vs conservative treatment ( CO ) in high-risk patients with acute cholecystitis . The study was r and omized and comprised 123 high-risk patients with acute cholecystitis . All patients fulfilled the ultrasonographic criteria of acute inflammation and had an APACHE II score ≥12 . Percutaneous cholecystostomy guided by US or CT was successful in 60 of 63 patients ( 95.2 % ) who comprised the PC group . Sixty patients were conservatively treated ( CO group ) . One patient died after unsuccessful PC ( 1.6 % ) . Resolution of symptoms occurred in 54 of 63 patients ( 86 % ) . Eleven patients ( 17.5 % ) died either of ongoing sepsis ( n=6 ) or severe underlying disease ( n=5 ) within 30 days . Seven patients ( 11 % ) were operated on because of persisting symptoms ( n=3 ) , catheter dislodgment ( n=3 ) , or unsuccessful PC ( n=1 ) . Cholecystolithotripsy was performed in 5 patients ( 8 % ) . Elective surgery was performed in 9 cases ( 14 % ) . No further treatment was needed in 32 patients ( 51 % ) . In the CO group , 52 patients ( 87 % ) fully recovered and 8 patients ( 13 % ) died of ongoing sepsis within 30 days . All successfully treated patients showed clinical improvement during the first 3 days of treatment . Percutaneous cholecystostomy in high-risk patients with acute cholecystitis did not decrease mortality in relation to conservative treatment . Percutaneous cholecystostomy might be suggested to patients not presenting clinical improvement following 3 days of conservative treatment , to critically ill intensive care unit patients , or to c and i date s for percutaneous cholecystolithotripsy", "OBJECTIVES To compare the demographic characteristics and intra- and postoperative outcomes in elderly adults ( ≥75 ) with those of younger adults undergoing early ( cholecystectomy . DESIGN Retrospective analysis from May 2010 to August 2012 . SETTING R and omized , multicenter , clinical trial ( ABCAL Study , NCT01015417 ) . PARTICIPANTS Individuals with mild or moderate acute calculous cholecystitis ( ACC ) according to the Tokyo Guidelines ( N=414 ; n=78 aged 75 - 94 , median 82 ; n=336 aged 18 - 74 , median 49 ) . MEASUREMENTS Demographic characteristics and pre- , intra- , and postoperative data . RESULTS The elderly group was more likely to have an American Society of Anesthesiologists score of 3 or greater ( 62 % vs 23 % , P higher serum creatinine ( 103 vs 74 μmol/L , P ACC ( moderate ACC ( 62 % vs 50 % , P=.05 ) , gangrenous cholecystitis ( 38 % vs 15 % , P=.001 ) ) on preoperative imaging and confirmed intraoperatively . Ulcerated mucosa ( 76 % vs 61 % , P=.001 ) was significantly more frequent in the elderly group . Operative time , postoperative mortality , and postoperative infectious ( 18 % vs 14 % , P=.35 ) and noninfectious ( 9 % vs 3 % , P=.80 ) complications were similar between the two groups . Median length of stay ( 7.0 vs 5.0 days , P=.54 ) and readmission rate ( 15 % vs 4 % , P=.07 ) were not significantly higher in the elderly group . No significant difference was observed for the subgroup of participants aged 80 and older . CONCLUSION In this r and omized trial that included a selected sample of older adults , there was no difference in major outcomes between elderly adults and their younger counterparts after early cholecystectomy . The findings are limited because important geriatric outcomes such as delirium and functional decline were not examined", "BACKGROUND AND STUDY AIMS Surgery in elderly patients with acute cholecystitis is quite a high-risk procedure . The recent finding that activated pancreatic enzyme is present in sterile bile from the acutely inflamed gallbladder suggests that obstruction at the level of the common channel is a possible precipitating factor . It was therefore hypothesized that an initial endoscopic sphincterotomy in patients with acute cholecystitis might improve the clinical course . PATIENTS AND METHODS A prospect i ve unselected series of 105 patients over 65 years of age ( 52 men , 53 women ; mean age 78 ) suffering from acute cholecystitis were initially treated on a r and om basis with either conservative methods or endoscopic sphincterotomy . Within the first 72 h after the onset of symptoms , all 52 patients in the endoscopic sphincterotomy group were managed by endoscopic retro grade cholangiopancreatography ( ERCP ) , combined with endoscopic sphincterotomy in 50 cases . The main study parameter was the need for emergency cholecystectomy within the first week after admission . RESULTS Biliary sepsis requiring emergency surgery occurred in 15 patients in the conservatively treated group , in contrast with none of the 52 patients in the endoscopic sphincterotomy group ( P Iatrogenic complications after endoscopic sphincterotomy occurred in three patients , one of whom required surgery , while two were managed by conservative means . The clinical course improved , avoiding the need for emergency cholecystectomy and other interventions , in 48 patients in the endoscopic sphincterotomy group and in 36 patients in the conservatively treated group ( P clinical course after endoscopic sphincterotomy improved in the majority of elderly patients suffering from acute cholecystitis , suggesting that early relief of obstruction at the level of the common channel reduces the risk of developing biliary sepsis . The majority of these patients can undergo surgery electively or can receive further conservative treatment" ]	41182c0a-06ff-11f0-808a-c43d1ab1c353
Background The aim of this meta- analysis was to compare the long-term efficacy of diet plus exercise ( D + E ) vs. diet ( D ) , D + E vs. exercise ( E ) and D vs. E on anthropometric outcomes and cardiovascular risk factors in overweight and obese participants . Methods Electronic search es were performed in MEDLINE and the Cochrane Central Register of controlled trials . Inclusion criteria were as follows : body mass index ≥25 kg/m2 and a minimum intervention period including follow-up of ≥12 months . Outcomes of interest were as follows : anthropometric parameters , blood lipids , blood pressure and cardiorespiratory fitness . Pooled effects were calculated using pairwise r and om effects and Bayesian r and om effects network meta- analysis . Results of the corresponding fixed effects models were compared in sensitivity analyses . Results Overall , 22 trials ( 24 reports ) met the inclusion criteria and 21 ( including 3,521 participants ) of them were included in the quantitative analysis . As compared with D , D + E result ed in a significantly more pronounced reduction in body weight [ mean differences ( MD ) : -1.38 kg , 95 % confidence interval ( CI ) -1.98 to -0.79 ] , and fat mass ( MD : -1.65 kg , 95 % CI -2.81 to -0.49 ] , respectively . When comparing D + E with E , MD in change of body weight ( -4.13 kg , 95 % CI -5.62 to -2.64 ) , waist circumference ( -3.00 cm , 95 % CI -5.81 to -0.20 ) , and fat mass ( -3.60 kg , 95 % CI -6.15 to -1.05 ) was in favour of combined diet and exercise , respectively . Comparing E vs. D , diet result ed in a significantly more pronounced decrease in body weight ( MD : -2.93 kg , 95 % CI -4.18 to -1.68 ) , and fat mass ( MD : -2.20 kg , 95 % CI -3.75 to -0.66 ) . D + E yielded also the greatest reductions with respect to blood lipids and blood pressure when compared to single applications of D and E , respectively . Results from the network meta-analyses confirmed these findings . Conclusions Moderate- quality evidence from the present network meta- analysis suggests that D + E can be highly recommended for long-term obesity management . Furthermore , the evidence suggests a moderate superiority of D over E with respect to anthropometric outcomes . Systematic review registration PROSPERO	[ "BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older adults ; however , the appropriate treatment for obese older adults is controversial . METHODS In this 1-year , r and omized , controlled trial , we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese . Participants were r and omly assigned to a control group , a weight-management ( diet ) group , an exercise group , or a weight-management-plus-exercise ( diet-exercise ) group . The primary outcome was the change in score on the modified Physical Performance Test . Secondary outcomes included other measures of frailty , body composition , bone mineral density , specific physical functions , and quality of life . RESULTS A total of 93 participants ( 87 % ) completed the study . In the intention-to-treat analysis , the score on the Physical Performance Test , in which higher scores indicate better physical status , increased more in the diet-exercise group than in the diet group or the exercise group ( increases from baseline of 21 % vs. 12 % and 15 % , respectively ) ; the scores in all three of those groups increased more than the scores in the control group ( in which the score increased by 1 % ) ( P peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group ( increases of 17 % vs. 10 % and 8 % , respectively ; P score on the Functional Status Question naire , in which higher scores indicate better physical function , increased more in the diet-exercise group than in the diet group ( increase of 10 % vs. 4 % , P Body weight decreased by 10 % in the diet group and by 9 % in the diet-exercise group , but did not decrease in the exercise group or the control group ( P Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group ( reductions of 3 % and 1 % , respectively , in the diet-exercise group vs. reductions of 5 % and 3 % , respectively , in the diet group ; P Strength , balance , and gait improved consistently in the diet-exercise group ( P musculoskeletal injuries . CONCLUSIONS These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00146107 . )", "BACKGROUND Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body , little information is available on the long-term effects on leptin concentrations of changes in diet and exercise . OBJECTIVE We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure , alone or in combination , affect plasma leptin concentrations . DESIGN In a r and omized , 2 x 2 factorial trial , 186 men with metabolic syndrome were divided into 4 groups : diet , exercise , a combination of diet and exercise , and control . Data on dietary intake , physical fitness , and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period . RESULTS Plasma leptin concentrations , body mass index , and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity . By adjusting for either body mass index or fat mass , we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions . There was no interaction between the interventions , suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations . CONCLUSION Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass", "BACKGROUND Persistent , low- grade inflammation is an independent predictor of several chronic diseases and all-cause mortality . OBJECTIVE The intention of this study was to determine the independent and combined effects of diet-induced weight loss and exercise on markers of chronic inflammation . DESIGN Three hundred sixteen community-dwelling , older ( > or = 60 y ) , overweight or obese [ body mass index ( in kg/m2 ) > or = 28 ] , sedentary men and women with radiographic evidence of knee osteoarthritis were r and omly assigned to four 18-mo treatments : healthy lifestyle control , diet-induced weight loss , exercise , and diet plus exercise . The exercise intervention consisted of combined weight training and walking for 1 h 3 times/wk . The weight-loss intervention consisted of a weekly session with a registered dietitian to provide education and support for lowering energy intake . RESULTS The diet-induced weight-loss intervention result ed in significantly greater reductions in concentrations of C-reactive protein ( P = 0.01 ) , interleukin 6 ( P = 0.009 ) , and soluble tumor necrosis factor alpha receptor 1 ( P = 0.007 ) than did no weight-loss treatment . Changes in soluble tumor necrosis factor alpha receptor 1 but not in C-reactive protein or interleukin 6 correlated with changes in body weight . Exercise training did not have a significant effect on these inflammatory biomarkers , and there was no significant interaction between weight loss and exercise training . CONCLUSIONS These findings provide evidence from a r and omized controlled trial that a dietary intervention design ed to elicit weight loss reduces overall inflammation in older , obese persons . Additional studies are needed to assess the effects of different modes and intensities of exercise on inflammation", "OBJECTIVE The Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) was a r and omized , single-blind clinical trial lasting 18 months that was design ed to determine whether long-term exercise and dietary weight loss are more effective , either separately or in combination , than usual care in improving physical function , pain , and mobility in older overweight and obese adults with knee osteoarthritis ( OA ) . METHODS Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older , with a body mass index of > or = 28 kg/m(2 ) , knee pain , radiographic evidence of knee OA , and self-reported physical disability , were r and omized into healthy lifestyle ( control ) , diet only , exercise only , and diet plus exercise groups . The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcomes included weight loss , 6-minute walk distance , stair-climb time , WOMAC pain and stiffness scores , and joint space width . RESULTS Of the 316 r and omized participants , 252 ( 80 % ) completed the study . Adherence was as follows : for healthy lifestyle , 73 % ; for diet only , 72 % ; for exercise only , 60 % ; and for diet plus exercise , 64 % . In the diet plus exercise group , significant improvements in self-reported physical function ( P 6-minute walk distance ( P stair-climb time ( P knee pain ( P 6-minute walk distance ( P . The weight-loss groups lost significantly ( P body weight ( for diet , 4.9 % ; for diet plus exercise , 5.7 % ) than did the healthy lifestyle group ( 1.2 % ) . Finally , changes in joint space width were not different between the groups . CONCLUSION The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone", "BACKGROUND Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus , but no large trials have compared interventions . We investigated the effects of diet and physical activity on blood pressure and glucose concentrations . METHODS We did a r and omised , controlled trial in southwest Engl and in adults aged 30 - 80 years in whom type 2 diabetes had been diagnosed 5 - 8 months previously . Participants were assigned usual care ( initial dietary consultation and follow-up every 6 months ; control group ) , an intensive diet intervention ( dietary consultation every 3 months with monthly nurse support ) , or the latter plus a pedometer-based activity programme , in a 2:5:5 ratio . The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c ) ) concentration and blood pressure at 6 months . Analysis was done by intention to treat . This study is registered , number IS RCT N92162869 . FINDINGS Of 593 eligible individuals , 99 were assigned usual care , 248 the diet regimen , and 246 diet plus activity . Outcome data were available for 587 ( 99 % ) and 579 ( 98 % ) participants at 6 and 12 months , respectively . At 6 months , glycaemic control had worsened in the control group ( mean baseline HbA(1c ) percentage 6·72 , SD 1·02 , and at 6 months 6·86 , 1·02 ) but improved in the diet group ( baseline-adjusted difference in percentage of HbA(1c ) -0·28 % , 95 % CI -0·46 to -0·10 ; p=0·005 ) and diet plus activity group ( -0·33 % , -0·51 to -0·14 ; p seen in bodyweight and insulin resistance between the intervention and control groups . Blood pressure was similar in all groups . INTERPRETATION An intensive diet intervention soon after diagnosis can improve glycaemic control . The addition of an activity intervention conferred no additional benefit . FUNDING Diabetes UK and the UK Department of Health", "BACKGROUND Caloric restriction ( CR ) increases maximal life span in short-lived organisms , and its effects are being explored in nonhuman primates . The objectives of this study were to determine the feasibility of prolonged CR in nonobese adults and to compare the effects of CR- and exercise-induced weight loss on body composition and abdominal adiposity . METHODS A r and omized , controlled trial was conducted with 48 healthy , nonobese women and men , aged 57 + /- 1 ( mean + /- st and ard error [ SE ] ) years , with body mass index 27.3 + /- 0.3 kg/m2 . Participants were r and omly assigned to a 20 % calorically-restricted diet ( CR , n = 19 ) , exercise design ed to produce a similar energy deficit ( EX , n = 19 ) , or a healthy lifestyle control group ( HL , n = 10 ) for 1 year . Assessment s included weight , body composition by dual-energy x-ray absorptiometry , abdominal adipose tissue by magnetic resonance imaging , and energy intake by doubly labeled water . RESULTS The average level of CR achieved by the CR group was 11.5 + /- 2.1 % , and the EX group completed 59 + /- 6.7 % of their prescribed exercise . Weight changes were greater ( p Whole-body fat mass and visceral and subcutaneous abdominal adipose tissue decreased significantly ( p CR and exercise were equally effective in reducing weight and adiposity", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "AIMS To study the long-term ( 1- and 2-year ) effect of a lifestyle intervention on non-diabetic first-degree relatives of type 2 diabetic patients , i.e. , the 1-year effect of diet versus diet and exercise in relation to a control group and the 2-year sustainability of these treatment effects . METHOD Seventy-seven healthy first-degree relatives ( men and women ) between the ages of 25 and 55 were allocated to one of three groups : diet group ( D ) , diet and exercise group ( DE ) and control group ( C ) . For ethical reasons , after 1 year the control group began the intervention and were followed for another 2 years . Diet and physical activity counselling was based on current nutrition recommendations , including increased intake of fatty fish and low glycaemic index foods . The fatty acid composition of the erythrocyte membrane was studied as an objective measure of dietary change . Assessment s included fasting insulin , 2-h insulin , oral glucose tolerance test ( OGTT ) , anthropometry and blood lipid measurements . Groups D and DE received intensive follow-up through unannounced telephone interviews during the first 4 months . RESULTS Dietary changes were significant at 1 year , and to a large degree sustained at 2 years . Adherence to advice regarding fat quality was confirmed through changes in the fatty acid composition of the erythrocyte membrane . The least active subjects in DE increased their physical activity ( PA ) . At 1 year , group D showed a reduction in the ratio of LDL to HDL cholesterol ( p=0.028 ) while group DE decreased their body weight by 2.7 % ( p HDL ( p cholesterol levels ( total , LDL and the ratio LDL/HDL ) were reduced within group D and when compared to DE ( p=0.022 , 0.009 , 0.035 , respectively ) . Fasting insulin was reduced within group DE and when compared to group D ( p=0.025 ) . CONCLUSIONS Positive changes in lifestyle , blood lipids and fasting insulin can be achieved and maintained in a non-diabetic population at risk of type 2 diabetes after 2 years", "BACKGROUND Maintenance of weight loss is a core problem in the treatment of obesity . Physical activity may improve maintenance and metabolic risk factors associated with obesity . HYPOTHESES ( 1 ) A walking training program of moderate intensity , started after weight reduction by a very-low-energy diet , improves maintenance of weight loss and obesity-related metabolic disorders ; and ( 2 ) the effect of the training program is related to the prescribed amount of physical activity , ie , a higher amount ( energy expenditure ) leads to more favorable results . METHODS The participants were premenopausal women with a mean body mass index of 34.0 kg/m(2 ) . Eighty-two participants were r and omized to this study ; 74 participated in the follow-up assessment . A 12-week weight reduction by mostly a very-low-energy diet was followed by a 40-week maintenance program r and omized in 3 groups : a control group with no increase in habitual exercise and with counseling on diet and relapse prevention ; a walk-1 group , with a walking program targeted to expend 4.2 MJ/wk and diet counseling ; and a walk-2 group , with a walking program of 8 . 4 MJ/wk and diet counseling . R and om permuted blocks within strata were used , with weight loss ( in 3 classes ) as the stratifying factor . After the intervention , the subjects were followed up for 2 years . MAIN OUTCOME MEASURES Primary outcomes were body weight , fat mass , and waist circumference at the 2-year follow-up . Secondary outcomes were the levels of serum lipoproteins and lipids , plasma glucose , insulin , and blood pressure . RESULTS The mean weight loss after weight reduction was 13.1 kg . The main outcome variables remained stable during the maintenance program , but increased during the follow-up period . Compared with the end of weight reduction , weight regain at the 2-year follow-up was 3.5 kg less ( 95 % confidence interval , 0.2 - 6.8 ) and waist circumference regain 3.8 cm less ( 95 % confidence interval , 0.3 - 7.3 ) in the walk-1 group vs controls . The secondary outcomes showed a partial relapse during the maintenance program , and a further regain during the follow-up period . CONCLUSIONS Inclusion of a walking program of moderate training regimen into a weight maintenance program improved maintenance of losses in weight and waist circumference", "BACKGROUND Increased physical activity is related to reduced risk of cardiovascular disease , possibly because it leads to improvement in the lipoprotein profile . However , the amount of exercise training required for optimal benefit is unknown . In a prospect i ve , r and omized study , we investigated the effects of the amount and intensity of exercise on lipoproteins . METHODS A total of 111 sedentary , overweight men and women with mild-to-moderate dyslipidemia were r and omly assigned to participate for six months in a control group or for approximately eight months in one of three exercise groups : high-amount-high-intensity exercise , the caloric equivalent of jogging 20 mi ( 32.0 km ) per week at 65 to 80 percent of peak oxygen consumption ; low-amount-high-intensity exercise , the equivalent of jogging 12 mi ( 19.2 km ) per week at 65 to 80 percent of peak oxygen consumption ; or low-amount-moderate-intensity exercise , the equivalent of walking 12 mi per week at 40 to 55 percent of peak oxygen consumption . Subjects were encouraged to maintain their base-line body weight . The 84 subjects who complied with these guidelines served as the basis for the main analysis . Detailed lipoprotein profiling was performed by nuclear magnetic resonance spectroscopy with verification by measurement of cholesterol in lipoprotein subfractions . RESULTS There was a beneficial effect of exercise on a variety of lipid and lipoprotein variables , seen most clearly with the high amount of high-intensity exercise . The high amount of exercise result ed in greater improvements than did the lower amounts of exercise ( in 10 of 11 lipoprotein variables ) and was always superior to the control condition ( 11 of 11 variables ) . Both lower-amount exercise groups always had better responses than the control group ( 22 of 22 comparisons ) . CONCLUSIONS The highest amount of weekly exercise , with minimal weight change , had widespread beneficial effects on the lipoprotein profile . The improvements were related to the amount of activity and not to the intensity of exercise or improvement in fitness", "Lifestyle interventions for weight loss are the cornerstone of obesity therapy , yet their optimal design is debated . This is particularly true for postmenopausal women ; a population with a high prevalence of obesity yet toward whom fewer studies are targeted . We conducted a year-long , 4-arm r and omized trial among 439 overweight-to-obese postmenopausal sedentary women to determine the effects of a calorie-reduced , low-fat diet ( D ) , a moderate-intensity , facility-based aerobic exercise program ( E ) , or the combination of both interventions ( D+E ) , vs. a no-lifestyle-change control ( C ) on change in body weight and composition . The group-based dietary intervention had a weight-reduction goal of ≥10 % , and the exercise intervention consisted of a gradual escalation to 45-min aerobic exercise 5 day/week . Participants were predominantly non-Hispanic whites ( 85 % ) with a mean age of 58.0 ± 5.0 years , a mean BMI of 30.9 ± 4.0 kg/m(2 ) and an average of 47.8 ± 4.4 % body fat . Baseline and 12-month weight and adiposity measures were obtained by staff blinded to participants ' intervention assignment . Three hundred and ninety nine women completed the trial ( 91 % retention ) . Using an intention-to-treat analysis , average weight loss at 12 months was -8.5 % for the D group ( P decrease . BMI , waist circumference , and % body fat were also similarly reduced . Among postmenopausal women , lifestyle-change involving diet , exercise , or both combined over 1 year improves body weight and adiposity , with the greatest change arising from the combined intervention", "Summary Two studies were conducted to determine whether adding exercise to a diet programme promotes weight loss or glycaemic control in Type 2 ( non-insulin-dependent ) diabetic subjects . In Study 1 , 25 subjects were r and omly assigned to diet plus moderate exercise or diet plus placebo exercise . All subjects exercised twice a week as a group and once a week on their own ; the diet plus moderate exercise group walked a 3-mile route at each session while the diet plus placebo exercise group did very low intensity exercises such as stretching and light calisthenics . All subjects followed a calorie-counting diet and were taught behaviour modification strategies . Weight losses and improvements in glycaemic control did not differ significantly between the two treatment groups at the end of the 10-week treatment or at 1-year follow-up . In Study 2 , more extreme conditions were compared : a diet only group and a diet plus exercise group . The diet plus exercise group walked a 3-mile route with the group 3 times/week and once a week on their own , while the diet only group was instructed to maintain their current low level of activity . Both groups received comparable diet and behaviour modification instruction and therapist contacts . The diet plus exercise group had significantly ( p better weight losses than the diet only condition at the end of the 10 week programme ( −9.3 kg vs −5.6 kg ) and at 1 year follow-up ( −7.9 kg vs −3.8 kg ) . Both groups had similar improvements in glycosylated haemoglobin , but reductions in medication were more frequent and greater in magnitude in the diet plus exercise group . Finally , analyses were conducted collapsing across studies and across treatment groups and comparing subjects who reported low , medium , or high levels of exercise at 1 year . Self-reported exercise was related to weight loss and to improvements in glycosylated haemoglobin , even after adjusting for weight loss . These data suggest that the combination of diet and exercise improves weight loss and glycaemic control compared to diet only in Type 2 diabetic patients", "We studied the effects of exercise ( primarily running ) , calorie restriction ( dieting ) , and a low-fat , high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a r and omized controlled clinical trial . After 1 year , complete data were obtained for 39 men assigned to lose weight through dieting without exercise , 37 men assigned to lose weight through dieting with exercise ( primarily running ) , and 40 nondieting sedentary controls . We instructed both diet groups to consume no more than 30 % total fat , 10 % saturated fat , and 300 mg/d of cholesterol , and at least 55 % carbohydrates , and the controls were instructed to maintain their usual food choices . Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations . In addition , the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein ( HDL ) subclasses that have been identified by their particle sizes , ie , HDL3c ( 7.2 to 7.8 nm ) , HDL3b ( 7.8 to 8.2 nm ) , HDL3a ( 8.2 to 8.8 nm ) , HDL2a ( 8.8 to 9.7 nm ) , and HDL2b ( 9.7 to 12 nm ) . Relative to controls , weight decreased significantly in men who dieted with exercise ( net difference + /- SE , -3.3 + /- 0.4 kg/m2 ) and in men who dieted without exercise ( -2.0 + /- 0.4 kg/m2 ) . Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass , HDL3a , HDL2a , and HDL2b relative to both control and dieting without exercise . There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE To assess the effect of lifestyle intervention over 2 years on changes in weight , coronary heart disease ( CHD ) risk factors , and incidence of diabetes in overweight individuals with a parental history of diabetes . RESEARCH DESIGN AND METHODS Participants ( n = 154 ) , who were 30–100 % over ideal body weight , had one or both parents with diabetes , and were currently nondiabetic , were r and omly assigned to 2-year treatments focused on diet ( decreasing calories and fat intake ) , exercise ( goal of 1,500 kcal/week of moderate activity ) , or the combination of diet plus exercise or to a no-treatment control group . Subjects were reassessed at 6 months , 1 year , and 2 years . RESULTS At 6 months , the groups differed significantly on measures of eating , exercise , and fitness ; weight losses in the diet and diet-plus-exercise groups were significantly > in the exercise and control conditions . Weight losses were associated with positive changes in CHD risk factors . After 6 months , there was gradual deterioration of behavioral and physiological changes , so that at 2 years , almost no between-group differences were maintained . Differences between groups in risk of developing diabetes were of borderline significance ( P = 0.08 ) . Strongest predictors were impaired glucose tolerance at baseline , which was positively related to risk of developing diabetes , and weight loss from baseline to 2 years , which was negatively related ; in all treatment groups , a modest weight loss of 4.5 kg reduced the risk of type 2 diabetes by ∼ 30 % compared with no weight loss . CONCLUSIONS Although initially successful , the interventions studied here were not effective in producing long-term changes in behavior , weight , or physiological parameters . However , weight loss from 0 to 2 years reduced the risk of developing type 2 diabetes . Since modest weight loss significantly reduced risk of type 2 diabetes , further research is needed to determine how best to increase the percentage of subjects achieving at least a modest weight loss ", "BACKGROUND The National Cholesterol Education Program ( NCEP ) recommends a low-saturated-fat , low-cholesterol diet , with weight loss if indicated , to correct elevated plasma cholesterol levels . Weight loss accomplished by simple caloric restriction or increased exercise typically increases the level of high-density lipoprotein ( HDL ) cholesterol . Little is known about the effects on plasma lipoproteins of a hypocaloric NCEP diet with or without exercise in overweight people . METHODS We tested the hypothesis that exercise ( walking or jogging ) will increase HDL cholesterol levels in moderately overweight , sedentary people who adopt a hypocaloric NCEP diet . We r and omly assigned 132 men and 132 women 25 to 49 years old to one of three groups : control , hypocaloric NCEP diet , or hypocaloric NCEP diet with exercise . One hundred nineteen of the men and 112 of the women returned for testing after one year . RESULTS After one year , the subjects in both intervention groups had reached or closely approached NCEP Step 1 dietary goals and reduced their mean body fat significantly ( range of reduction in mean fat weight , 4.0 to 7.8 kg ) . Weight loss on the NCEP diet alone did not significantly change HDL cholesterol levels in either the men or the women as compared with the subjects in the control group . Plasma levels of HDL cholesterol increased significantly more in the men who exercised and dieted ( mean [ + /- SE ] change , + 13 + /- 3 percent ) than in the men who only dieted ( + 2 + /- 3 percent , P less than 0.01 ) or the men who acted as controls ( -4 + /- 2 percent , P less than 0.001 ) . HDL cholesterol levels remained about the same in the women who exercised and dieted ( + 1 + /- 2 percent ) ; they were higher than in the women who only dieted ( -10 + /- 3 percent , P less than 0.01 ) , but not higher than in the controls ( -3 + /- 3 percent ) . CONCLUSIONS Regular exercise in overweight men and women enhances the improvement in plasma lipoprotein levels that results from the adoption of a low-saturated-fat , low-cholesterol diet", "Objective : To investigate the effect of diet alone ( D ) , exercise alone ( E ) , and a combination of diet and exercise ( DE ) on body weight , body composition , energy intake , blood pressure , serum lipid and leptin levels , and fitness levels in mildly obese sedentary women and men . Design : The three interventions were compared in a r and omized longitudinal study design . The exercise programs were supervised for six months , after which participants in E and DE were provided with exercise equipment to take home . Subjects : 90 adult overweight women and men ( age : 44.2 ± 7.2 years ; BMI = 30.5 ± 2.7 kg/m2 ) . Measurements : Body weight , body composition , waist and hip circumferences , blood pressure , serum lipid levels , and fitness levels were evaluated at 0 , 3 , 6 , 9 , and 12 months . Serum leptin concentrations were measured at 0 and 6 months only . Results : At 6 and 9 months in women , and 9 months in men , DE demonstrated a significant loss of body weight compared to both D and E ( p significantly decreased from baseline to 6 months in women in D ( p = 0.05 ) and DE ( p = 0.0003 ) and men in E ( p = 0.038 ) . At one year , no significant differences existed among groups in any of the measures . Conclusion : A combination of diet and exercise result ed in a significant decrease in body weight in women and men ; but this decrease was not maintained at one year follow-up . Serum leptin concentrations showed significant within-group decreases , but were not different among groups . A supervised diet and exercise program is effective for weight loss ; however , once intensive participant-investigator and participant-participant contact is discontinued , weight regain ensures", "BACKGROUND Guidelines established by the National Cholesterol Education Program ( NCEP ) promote exercise and weight loss for the treatment of abnormal lipoprotein levels . Little is known , however , about the effects of exercise or the NCEP diet , which is moderately low in fat and cholesterol , in persons with lipoprotein levels that place them at high risk for coronary heart disease . METHODS We studied plasma lipoprotein levels in 180 postmenopausal women , 45 through 64 years of age , and 197 men , 30 through 64 years of age , who had low high-density lipoprotein ( HDL ) cholesterol levels ( lipoprotein ( LDL ) cholesterol ( > 125 mg per deciliter but 125 mg per deciliter but The subjects were r and omly assigned to aerobic exercise , the NCEP Step 2 diet , or diet plus exercise , or to a control group , which received no intervention . RESULTS Dietary intake of fat and cholesterol decreased during the one-year study ( P body weight , in women and men in either the diet group or the diet-plus-exercise group , as compared with the controls ( P dietary intake and body weight were unchanged . Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups , for subjects of either sex . The serum level of LDL cholesterol was significantly reduced among women ( a decrease of 14.5+/-22.2 mg per deciliter ) and men ( a decrease of 20.0+/-17.3 mg per deciliter ) in the diet-plus-exercise group , as compared with the control group ( women had a decrease of 2.5+/-16.6 mg per deciliter , P reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group ( 3.6+/-18.8 mg per deciliter , P LDL cholesterol levels were not significant among the women ( a decrease of 7.3+/-18.9 mg per deciliter ) or the men ( 10.8+/-18.8 mg per deciliter ) in the diet group , as compared with the controls . CONCLUSIONS The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise . This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels", "OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT", "Objective : To investigate whether walking or resistance training improves weight maintenance after weight loss when added to dietary counselling . Design : Two months ' weight reduction with very-low-energy-diet ( VLED ) followed by r and omization into three groups ( control , walking , resistance training ) for 6 months ' weight maintenance ( WM ) program and 23 months ' unsupervised follow-up . During VLED and WM all groups received similar dietary counselling . Subjects : The main inclusion criteria were BMI > 30 kg/m2 , waist>100 cm and physical inactivity ( exercise ≤ once a week ) . Ninety healthy , obese ( mean BMI 32.9 kg/m2 and waist 112.5 cm ) , 35–50 y-old men started the study and 68 were measured at the end of the study . Measurements : Weight and body composition assessed by underwater weighing . Exercise diaries and dietary records to assess energy balance . Results : During VLED the mean body weight decreased from 106.0 ( s.d . 9.9 ) kg to 91.7 ( 9.4 ) kg . Weight was regained mostly during follow-up and in the end of the study the mean weight in groups was 99.9–102.0 kg . Exercise training did not improve short or long-term weight maintenance when compared to the control group . However , resistance training attenuated the regain of body fat mass during WM ( P=0.0l ) , but not during follow-up . In the combined groups the estimated total energy expenditure ( EE ) of reported physical activity was associated with less weight regain during WM . EE of 10.1 MJ/week was associated with maintaining weight after weight loss . EE of physical activity tended to decrease after WM in exercise groups due to poor long-term adherence to prescribed exercise . Energy intake seemed to increase during follow-up . Conclusion : Exercise training of moderate dose did not seem to improve long-term weight maintenance because of poor adherence to prescribed exercise", "We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men -- decreasing energy intake without increasing exercise ( diet ) , and increasing energy expenditure without altering energy intake ( exercise , primarily running)--in a one-year r and omized controlled trial . As compared with controls ( n = 42 ) , dieters ( n = 42 ) had significant loss of total body weight ( -7.8 + /- 0.9 kg [ mean + /- SE ] ) , fat weight ( -5.6 + /- 0.8 kg ) , and lean ( non-fat ) weight ( -2.1 + /- 0.5 kg ) ( P less than 0.001 for each variable ) , and exercisers ( n = 47 ) had significant loss of total body weight ( -4.6 + /- 0.8 kg ) and fat weight ( -3.8 + /- 0.7 kg ) ( P less than 0.001 for both variables ) but not lean weight ( -0.7 + /- 0.4 kg ) . Fat-weight loss did not differ significantly between dieters and exercisers . All subjects were discouraged from altering their diet composition ; however , dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat . As compared with the control group , both weight-loss groups had significant increases ( P less than 0.01 ) in plasma concentrations of high-density lipoprotein ( HDL ) cholesterol ( diet vs. exercise , 0.13 + /- 0.03 vs. 0.12 + /- 0.03 mmol per liter ) , HDL2 cholesterol ( 0.07 + /- 0.02 vs. 0.07 + /- 0.02 mmol per liter ) , and HDL3 cholesterol ( 0.07 + /- 0.02 vs. 0.06 + /- 0.02 mmol per liter ) and significant decreases ( P less than 0.05 ) in triglyceride levels ( diet vs. exercise , -0.35 + /- 0.14 vs. -0.24 + /- 0.12 mmol per liter ) . Levels of total and low-density lipoprotein cholesterol were not significantly changed , relative to values in controls . None of these changes were significantly different between dieters and exercisers . Thus , we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations", "This study reports results 1 year after treatment for 77 obese women who had been treated for 48 weeks by diet combined with supervised ( a ) aerobic exercise , ( b ) strength training , ( c ) aerobic plus strength training combined , or ( d ) no exercise . Mean ( + /- SD ) end-of-treatment weight losses for the 4 conditions ranged from 13.5 + /- 9.1 kg to 17.3 + /- 10.3 kg , but there were no statistically significant differences among groups . Participants in all 4 conditions regained approximately 35 % to 55 % of their weight loss in the year after treatment ; again , there were no significant differences among groups . Participants , however , who reported exercising regularly in the 4 months preceding the follow-up assessment regained significantly less weight than did nonexercisers", "OBJECTIVE Obese patients with knee osteoarthritis ( OA ) are encouraged to lose weight to obtain symptomatic relief . Risk of vascular events is higher in people with OA compared to people without arthritis . Our aim in this r and omized trial was to compare changes in cardiovascular disease ( CVD ) risk-factors , nutritional health , and body composition after 1-year weight-loss maintenance achieved by [D]diet , [E]knee-exercise , or [C]control , following weight loss by low-energy-diet . DESIGN AND METHODS Obese individuals ( n = 192 , > 50 years ) with knee OA , 63 years ( SD 6 ) , weight 103.2 kg ( 15.0 ) , body-mass index 37.3 kg/m(2 ) ( 4.8 ) , were enrolled into a 68-week weight-loss trial . RESULTS Mean changes in weight , in D , E , and C were -11.0 , -6.3 , and -8.3 kg ( P = 0.002 ) . Reduction in waist circumference in D , E , and C were -8.4 , -4.6 , and -7.0 cm ( P = 0.007 ) . D reduced waist circumference significantly more than E : -3.8 cm ( 95%CI -6.2 to -1.4 ; P = 0.0024 ) . There was no difference between the groups in changes in CVD risk factors ; blood pressure , triglycerides , and cholesterol . Nutritional health was improved in all groups . For markers of bone , no statistical difference was found between the groups . CONCLUSIONS Dietary support , or control , maintained improvements in cardiovascular risk factors to the same extent and none of the interventions had a detrimental effect on bone", "CONTEXT Physical inactivity contributes to weight gain , but only 22 % of Americans are regularly active . OBJECTIVE To examine short- and long-term changes in weight , body composition , and cardiovascular risk profiles produced by diet combined with either structured aerobic exercise or moderate-intensity lifestyle activity . DESIGN Sixteen-week r and omized controlled trial with 1-year follow-up , conducted from August 1995 to December 1996 . PARTICIPANTS AND SETTING Forty obese women ( mean body mass index [ weight in kilograms divided by the square of height in meters ] , 32.9 kg/m2 ; mean weight , 89.2 kg ) with a mean age of 42.9 years ( range , 21 - 60 years ) seen in a university-based weight management program . INTERVENTIONS Structured aerobic exercise or moderate lifestyle activity ; low-fat diet of about 1200 kcal/d . MAIN OUTCOME MEASURES Changes in body weight , body composition , cardiovascular risk profiles , and physical fitness at 16 weeks and at 1 year . RESULTS Mean ( SD ) weight losses during the 16-week treatment program were 8.3 ( 3.8 ) kg for the aerobic group and 7.9 ( 4.2 ) kg for the lifestyle group ( within groups , P less fat-free mass ( 0.5 [ 1.3 ] kg ) than the lifestyle group ( 1.4 [ 1.3 ] kg ; P = .03 ) . During the 1-year follow-up , the aerobic group regained 1.6 [ 5.5 ] kg , while the lifestyle group regained 0.08 ( 4.6 ) kg . At week 16 , serum triglyceride levels and total cholesterol levels were reduced significantly ( P program of diet plus lifestyle activity may offer similar health benefits and be a suitable alternative to diet plus structured aerobic activity for obese women", "OBJECTIVE To compare changes in total and regional body composition using dual energy X-ray absorptiometry ( DEXA ) after subjects lost weight through change in diet or exercise . DESIGN A 12-month , r and omized , controlled study of two weight-loss interventions -low-fat diet ad libitum or moderate , unsupervised exercise-in free-living , middle-aged men . Compliance was determined at monthly measurement sessions through food records and activity logs ; DEXA scans were performed every 3 months . SUBJECTS/ SETTING Fifty-eight overweight men ( mean body mass index = 29.0 + /- 2.6 ; mean age = 43.4 + /- 5.7 years ) recruited from a national corporation were assigned r and omly to diet , exercise , or control groups . INTERVENTIONS One group reduced dietary fat to 26.4 % of energy intake but kept activity unchanged ; another group self-selected aerobic exercise ( three sessions per week at 65 % to 75 % maximum heart rate ) but kept diet unchanged . A control group maintained weight . MAIN OUTCOME MEASURES At 12 months , measurements of weight , total and regional fat mass and lean mass , energy intake , and percentage dietary fat ; physical activity indexes . STATISTICAL ANALYSES Results were analyzed using paired t tests and analysis of variance . RESULTS Mean weight loss was 6.4 + /- 3.3 kg in dieters and 2.6 + /- 3.0 kg in exercisers ; control subjects maintained weight . DEXA scans revealed that 40 % of dieters ' weight loss was lean tissue ; more than 80 % of weight lost by exercisers was fat . Exercisers maintained limb lean tissue and lost fat mass . CONCLUSIONS Greater total weight and lean tissue loss occurred when subjects lost weight through a low-fat diet consumed ad libitum than when subjects participated in unsupervised aerobic exercise . Use of DEXA enabled identification of progressive total and regional changes in fat and lean tissue", "OBJECTIVE The effects of three cognitive-behavioral weight control interventions for adults were compared : diet only , exercise only , and a combination of diet and exercise . This article reports 2-year follow-up data . DESIGN The three interventions were compared in a r and omized , experimental design . SUBJECTS A total of 127 men and women who were at least 14 kg overweight ( according to height-weight tables ) were recruited from an urban community and assigned r and omly to the experimental conditions . INTERVENTION The dietary intervention was a low-energy eating plan adjusted to produce a 1 kg/week loss of weight . The exercise component involved training in walking and a home-based program of up to five exercise periods per week . There were 12 weekly instructional sessions , followed by 3 biweekly and 8 monthly meetings . All sessions were led by registered dietitians . OUTCOME MEASURES Changes in body weight . STATISTICAL ANALYSES Analysis of variance for weight changes and repeated measures analysis of variance for weight change trends . RESULTS At 1 year , no significant differences were noted among the three groups . The diet-only group lost 6.8 kg , the exercise-only group lost 2.9 kg , and the combination group lost 8.9 kg ( P=.09 ) . During the second year , the diet-only group regained weight -- reaching 0.9 kg above baseline ; the combination group regained to 2.2 kg below baseline ; and the exercise-only group regained slightly to 2.7 kg below baseline ( P=.36 ) . Repeated measures analysis of variance showed a group-by-time interaction ( P=.001 ) ; data for the dieting groups best fit a U-shaped regain curve ( P=.001 ) . APPLICATIONS The results suggest that dieting is associated with weight loss followed by regain after treatment ends , whereas exercise alone produced smaller weight losses but better maintenance . The large outcome variability and unequal difficulty of the regimens across groups limit the generalizability of the findings", "IMPORTANCE Knee osteoarthritis ( OA ) , a common cause of chronic pain and disability , has biomechanical and inflammatory origins and is exacerbated by obesity . OBJECTIVE To determine whether a ≥10 % reduction in body weight induced by diet , with or without exercise , would improve mechanistic and clinical outcomes more than exercise alone . DESIGN , SETTING , AND PARTICIPANTS Single-blind , 18-month , r and omized clinical trial at Wake Forest University between July 2006 and April 2011 . The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program . Participants were 454 overweight and obese older community-dwelling adults ( age ≥55 years with body mass index of 27 - 41 ) with pain and radiographic knee OA . INTERVENTIONS Intensive diet-induced weight loss plus exercise , intensive diet-induced weight loss , or exercise . MAIN OUTCOMES AND MEASURES Mechanistic primary outcomes : knee joint compressive force and plasma IL-6 levels ; secondary clinical outcomes : self-reported pain ( range , 0 - 20 ) , function ( range , 0 - 68 ) , mobility , and health-related quality of life ( range , 0 - 100 ) . RESULTS Three hundred ninety-nine participants ( 88 % ) completed the study . Mean weight loss for diet + exercise participants was 10.6 kg ( 11.4 % ) ; for the diet group , 8.9 kg ( 9.5 % ) ; and for the exercise group , 1.8 kg ( 2.0 % ) . After 18 months , knee compressive forces were lower in diet participants ( mean , 2487 N ; 95 % CI , 2393 to 2581 ) compared with exercise participants ( 2687 N ; 95 % CI , 2590 to 2784 , pairwise difference [Δ](exercise vs diet ) = 200 N ; 95 % CI , 55 to 345 ; P = .007 ) . Concentrations of IL-6 were lower in diet + exercise ( 2.7 pg/mL ; 95 % CI , 2.5 to 3.0 ) and diet participants ( 2.7 pg/mL ; 95 % CI , 2.4 to 3.0 ) compared with exercise participants ( 3.1 pg/mL ; 95 % CI , 2.9 to 3.4 ; Δ(exercise vs diet + exercise ) = 0.39 pg/mL ; 95 % CI , -0.03 to 0.81 ; P = .007 ; Δ(exercise vs diet ) = 0.43 pg/mL ; 95 % CI , 0.01 to 0.85 , P = .006 ) . The diet + exercise group had less pain ( 3.6 ; 95 % CI , 3.2 to 4.1 ) and better function ( 14.1 ; 95 % CI , 12.6 to 15.6 ) than both the diet group ( 4.8 ; 95 % CI , 4.3 to 5.2 ) and exercise group ( 4.7 ; 95 % CI , 4.2 to 5.1 , Δ(exercise vs diet + exercise ) = 1.02 ; 95 % CI , 0.33 to 1.71 ; P(pain ) = .004 ; 18.4 ; 95 % CI , 16.9 to 19.9 ; Δ(exercise vs diet + exercise ) , 4.29 ; 95 % CI , 2.07 to 6.50 ; P(function ) ) . The diet + exercise group ( 44.7 ; 95 % CI , 43.4 to 46.0 ) also had better physical health-related quality of life scores than the exercise group ( 41.9 ; 95 % CI , 40.5 to 43.2 ; Δ(exercise vs diet + exercise ) = -2.81 ; 95 % CI , -4.76 to -0.86 ; P = .005 ) . CONCLUSIONS AND RELEVANCE Among overweight and obese adults with knee OA , after 18 months , participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group ; those in the diet group had greater reductions in knee compressive force than those in the exercise group . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00381290" ]	41182c82-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES Our aim is to present a summary of the 2010 version of the European Association of Urology ( EAU ) guidelines on the treatment of advanced , relapsing , and castration-resistant prostate cancer ( CRPC ) . METHODS The working panel performed a literature review of the new data emerging from 2007 to 2010 . The guidelines were up date d , and the levels of evidence ( LEs ) and /or grade s of recommendation ( GR ) were added to the text based on a systematic review of the literature , which included a search of online data bases and bibliographic review s. RESULTS Luteinising hormone-releasing hormone ( LHRH ) agonists are the st and ard of care in metastatic prostate cancer ( PCa ) . Although LHRH antagonists decrease testosterone without any testosterone surge , their clinical benefit remains to be determined . Complete and rogen blockade has a small survival benefit of about 5 % . Intermittent and rogen deprivation ( IAD ) results in equivalent oncologic efficacy when compared with continuous and rogen-deprivation therapy ( ADT ) in well-selected population s. In locally advanced and metastatic PCa , early ADT does not result in a significant survival advantage when compared with delayed ADT . Relapse after local therapy is defined by prostate-specific antigen ( PSA ) values > 0.2 ng/ml following radical prostatectomy ( RP ) and > 2 ng/ml above the nadir after radiation therapy ( RT ) . Therapy for PSA relapse after RP includes salvage RT at PSA levels salvage RP or cryosurgical ablation of the prostate in radiation failures . Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography ( CT ) are of limited importance if the PSA is 20 ng/ml . Follow-up after ADT should include screening for the metabolic syndrome and an analysis of PSA and testosterone levels . Treatment of castration-resistant prostate cancer ( CRPC ) includes second-line hormonal therapy , novel agents , and chemotherapy with docetaxel at 75 mg/m(2 ) every 3 wk . Cabazitaxel as a second-line therapy for relapse after docetaxel might become a future option . Zoledronic acid and denusomab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications . CONCLUSION The knowledge in the field of advanced , metastatic , and CRPC is rapidly changing . These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice . A full version is available at the EAU office or online at www.uroweb.org	[ "BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P soft-tissue response rate ( 29 % vs. 4 % , P quality -of-life response rate ( 43 % vs. 18 % , P time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . )", "PURPOSE To assess whether the risk of death is associated with the time to testosterone recovery ( TTR ) after radiotherapy ( RT ) and hormonal therapy ( HT ) for prostate cancer ( PCa ) . PATIENTS AND METHODS Between 1995 and 2001 , 206 men with localized , unfavorable-risk PCa were r and omized to receive RT or RT plus 6 months of HT . A multivariate postr and omization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors , age , Adult Comorbidity Evaluation-27 score , and the use of HT for recurrence . RESULTS Of the 102 men r and omized to receive RT and HT , 57 ( 56 % ) had a TTR of > 2 years , and none of these men had died of PCa after a median follow-up of 7.6 years . As the TTR increased , the risk of death decreased significantly ( adjusted hazard ratio , 0.60 ; 95 % confidence interval , 0.43 - 0.84 ; p = .003 ) . A significant interaction was noted between the TTR and the comorbidity score ( p = .002 ) . The survival estimates were similar ( p = 0.17 ) across the TTR values in men with moderate to severe comorbidity ; however , these estimates increased significantly ( p PCa-specific mortality ( p = .006 ) as the TTR increased in men with no or minimal comorbidity . CONCLUSION The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity", "We conducted a r and omized clinical trial in men with stage D2 prostate cancer to test whether and rogen priming potentiates the efficacy of cytotoxic chemotherapy . Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal and rogen secretion and were administered cyclic intravenous ( IV ) chemotherapy . The patients were r and omized to receive either and rogen priming or no additional treatment for three days before and on the day of chemotherapy . Median duration of follow-up was 43 months . Response rate ( remission plus disease stabilization ) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients ( 79 % v 73 % , respectively ) or when it was extended to all patients ( 46 % v 61 % ) . Median duration of response was similar for the stimulation and control arm ( 9 and 10 months , respectively ) . Median survival was 10 months in the stimulation and 15 months in the control group ( P = .0047 ) . The and rogen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with and rogen administration . Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit , long duration of response to the initial castration , and normalization of an elevated serum acid phosphatase on treatment . We conclude that in this group of patients with advanced disease , and rogen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome . Furthermore , our data emphasize the heterogeneity of biologic behavior of prostate cancer", "BACKGROUND Previous r and omised trials demonstrated that adjuvant radiation therapy ( aRT ) improves cancer control in patients with pT3 prostate cancer ( PCa ) . However , there is currently no evidence supporting early salvage radiation therapy ( eSRT ) as equivalent to aRT in improving freedom from biochemical recurrence ( BCR ) after radical prostatectomy ( RP ) . OBJECTIVE To evaluate BCR-free survival for aRT versus observation followed by eSRT in cases of relapse in patients undergoing RP for pT3pN0 , R0-R1 PCa . DESIGN , SETTING , AND PARTICIPANTS Using a European multi-institutional cohort , 890 men with pT3pN0 , R0-R1 PCa were identified . INTERVENTION All patients underwent RP . Subsequently , patients were stratified into two groups : aRT versus initial observation followed by eSRT in cases of relapse . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES : Propensity-matched analysis was employed , and patients were stratified into two groups : aRT versus observation and eventual eSRT , defined as RT given at a postoperative serum prostate-specific antigen ( PSA ) ≤ 0.5 ng/ml at least 6 mo after RP . BCR , defined as PSA > 0.20 ng/ml and rising after administration of RT , was compared between aRT and initial observation followed by eSRT in cases of relapse using Kaplan-Meier and Cox regression methods . RESULTS AND LIMITATIONS Overall , 390 ( 43.8 % ) and 500 ( 56.2 % ) patients were treated with aRT and initial observation , respectively . Within the latter group , 225 ( 45.0 % ) patients experienced BCR and underwent eSRT . In the postpropensity-matched cohort , the 2- and 5-yr BCR-free survival rates were 91.4 % and 78.4 % in aRT versus 92.8 % and 81.8 % in patients who underwent initial observation and eSRT in cases of relapse , respectively ( p=0.9 ) . No differences in the 2- and 5-yr BCR-free survival rates were found , even when patients were stratified according to pT3 substage and surgical margin status ( all p ≥ 0.4 ) . These findings were also confirmed in multivariable analyses ( p=0.6 ) . Similar results were achieved when the cut-off to define eSRT was set at 0.3 ng/ml ( all p ≥ 0.5 ) . CONCLUSIONS The current study suggests that timely administration of eSRT is comparable to aRT in improving BCR-free survival in the majority of pT3pN0 PCa patients . Therefore , eSRT may not compromise cancer control but significantly reduces overtreatment associated with aRT", " To evaluate the efficacy and safety of degarelix , a new gonadotrophin‐releasing hormone ( GnRH ) antagonist ( blocker ) , vs leuprolide for achieving and maintaining testosterone suppression in a 1‐year phase III trial involving patients with prostate cancer", "PURPOSE To up date eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone . METHODS A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by review ing previous criteria , Response Evaluation Criteria in Solid Tumors ( RECIST ) , and emerging trial data . RESULTS The Prostate Cancer Clinical Trials Working Group ( PCWG2 ) recommends a two- objective paradigm : ( 1 ) controlling , relieving , or eliminating disease manifestations that are present when treatment is initiated and ( 2 ) preventing or delaying disease manifestations expected to occur . Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory . Eligibility is defined using st and ard disease assessment s to authenticate disease progression , prior treatment , distinct clinical subtypes , and predictive models . Outcomes are reported independently for prostate-specific antigen ( PSA ) , imaging , and clinical measures , avoiding grouped categorizations such as complete or partial response . In most trials , early changes in PSA and /or pain are not acted on without other evidence of disease progression , and treatment should be continued for at least 12 weeks to ensure adequate drug exposure . Bone scans are reported as \" new lesions \" or \" no new lesions , \" changes in soft-tissue disease assessed by RECIST , and pain using vali date d scales . Defining eligibility for prevent/delay end points requires attention to estimated event frequency and /or r and om assignment to a control group . CONCLUSION PCWG2 recommends increasing emphasis on time-to-event end points ( ie , failure to progress ) as decision aids in proceeding from phase II to phase III trials . Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit", "PURPOSE Prostate-specific antigen ( PSA ) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells . For patients with metastatic disease , changes in PSA will often ante date changes in bone scan . Furthermore , many but not all investigators have observed an association between a decline in PSA levels of 50 % or greater and survival . Since the majority of phase II clinical trials for patients with and rogen-independent prostate cancer ( AIPC ) have used PSA as a marker , we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting . We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters . RESULT We defined four patient groups : ( 1 ) progressive measurable disease , ( 2 ) progressive bone metastasis , ( 3 ) stable metastases and a rising PSA , and ( 4 ) rising PSA and no other evidence of metastatic disease . The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials . We propose that investigators report at a minimum a PSA decline of at least 50 % and this must be confirmed by a second PSA value 4 or more weeks later . Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period . Some investigators may want to report additional measures of PSA changes ( ie , 75 % decline , 90 % decline ) . Response duration and the time to PSA progression may also be important clinical end point . CONCLUSION Through this consensus conference , we believe we have developed practical guidelines for using PSA as a measurement of outcome . Furthermore , the use of common st and ards is important as we determine which agents should progress to r and omized trials which will use survival as an end point", "BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 .", "BACKGROUND Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving and rogen-deprivation therapy . Replacing and rogens before progression of the disease is hypothesized to prolong and rogen dependence . METHODS Men with newly diagnosed , metastatic , hormone-sensitive prostate cancer , a performance status of 0 to 2 , and a prostate-specific antigen ( PSA ) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an anti and rogen agent for 7 months . We then r and omly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent and rogen deprivation , with patients stratified according to prior or no prior hormonal therapy , performance status , and extent of disease ( minimal or extensive ) . The co primary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival , with a one-sided test with an upper boundary of the hazard ratio of 1.20 , and whether quality of life differed between the groups 3 months after r and omization . RESULTS A total of 3040 patients were enrolled , of whom 1535 were included in the analysis : 765 r and omly assigned to continuous and rogen deprivation and 770 assigned to intermittent and rogen deprivation . The median follow-up period was 9.8 years . Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group ( hazard ratio for death with intermittent therapy , 1.10 ; 90 % confidence interval , 0.99 to 1.23 ) . Intermittent therapy was associated with better erectile function and mental health ( P treatment-related high- grade adverse events . CONCLUSIONS Our findings were statistically inconclusive . In patients with metastatic hormone-sensitive prostate cancer , the confidence interval for survival exceeded the upper boundary for noninferiority , suggesting that we can not rule out a 20 % greater risk of death with intermittent therapy than with continuous therapy , but too few events occurred to rule out significant inferiority of intermittent therapy . Intermittent therapy result ed in small improvements in quality of life . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT00002651 . )", "OBJECTIVES To evaluate the efficacy , tolerability , endocrinological effects and the pharmacokinetics of Casodex , when given as monotherapy during daily dosing of 10 - 200 mg to patients with advanced prostate cancer . METHODS A total of 390 patients with advanced prostate cancer were treated for a minimum of 12 weeks with a daily monotherapy dose of Casodex . The doses ranged from 10 to 200 mg . Objective assessment s of efficacy included : review of measurable metastases , prostate dimension , prostatic acid phosphatase and prostate-specific antigen ( PSA ) levels . Subjective assessment s of efficacy included review of urological symptoms , performance status , bone scan and analgesic requirement . Pharmacokinetic sample s were taken at various time points up to 3 months , and assayed using an achiral HPLC method . RESULTS Clear objective responses were observed , particularly at doses of 50 mg and above . Specifically , the median percentage decrease in PSA at 50 mg was 90.0 % , and at 100 and 200 mg it was 93.4 and 94.8 % , respectively . Up to 53 % of symptomatic patients demonstrated a subjective response at 3 months . Casodex was well tolerated at all doses with no effect on haematological or cardiovascular parameters and no effect on renal function . The expected pharmacological effects of potent anti and rogen therapy , such as breast tenderness ( 58 % ) , gynaecomastia ( 48 % ) , and hot flushes ( 17 % ) , were reported , but these incidences reflected the direct eliciting of these events . The intrinsic efficacy of Casodex was demonstrated despite increases of 60 % in testosterone levels . However , this increase reached a plateau after 4 - 12 weeks of therapy , but the majority of values remained within the normal range . Casodex has a half-life of approximately 1 week , enabling once-daily dosing with no effect of age or renal impairment on its pharmacokinetics . CONCLUSION Casodex has a favourable side effect profile compared with the known safety profiles of other anti and rogens and has demonstrated intrinsic efficacy . Casodex warrants further investigation as a monotherapy for the management of advanced prostate cancer", "OBJECTIVE To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment ( IMPACT ) trial who were r and omized to receive sipuleucel-T or control . METHODS The most powerful of these prognostic factors , baseline prostate-specific antigen ( PSA ) , was subdivided into quartiles to evaluate treatment effect patterns . Cox regression analyses were used to assess predictors of overall survival ( OS ) and sipuleucel-T treatment effect within PSA quartiles . Median OS was estimated by the Kaplan-Meier method . RESULTS PSA was the strongest baseline prognostic factor ( P the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA . The OS hazard ratio for patients in the lowest baseline PSA quartile ( ≤22.1 ng/mL ) was 0.51 ( 95 % confidence interval , 0.31 - 0.85 ) compared with 0.84 ( 95 % confidence interval , 0.55 - 1.29 ) for patients in the highest PSA quartile ( > 134 ng/mL ) . Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile . Estimated 3-year survival in the lowest PSA quartile was 62.6 % for sipuleucel-T patients and 41.6 % for control patients , representing a 50 % relative increase . CONCLUSION The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors , particularly those with lower baseline PSA values . These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer", "BACKGROUND Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced , hormone-refractory prostate cancer , but it does not improve survival . We compared such treatment with docetaxel plus prednisone in men with this disease . METHODS From March 2000 through June 2002 , 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were r and omly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks , 75 mg of docetaxel per square meter every three weeks , or 30 mg of docetaxel per square meter weekly for five of every six weeks . The primary end point was overall survival . Secondary end points were pain , prostate-specific antigen ( PSA ) levels , and the quality of life . All statistical comparisons were against mitoxantrone . RESULTS As compared with the men in the mitoxantrone group , men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 ( 95 percent confidence interval , 0.62 to 0.94 ; P=0.009 by the stratified log-rank test ) and those given weekly docetaxel had a hazard ratio for death of 0.91 ( 95 percent confidence interval , 0.75 to 1.11 ; P=0.36 ) . The median survival was 16.5 months in the mitoxantrone group , 18.9 months in the group given docetaxel every 3 weeks , and 17.4 months in the group given weekly docetaxel . Among these three groups , 32 percent , 45 percent , and 48 percent of men , respectively , had at least a 50 percent decrease in the serum PSA level ( P mitoxantrone ) ; 22 percent , 35 percent ( P=0.01 ) , and 31 percent ( P=0.08 ) had predefined reductions in pain ; and 13 percent , 22 percent ( P=0.009 ) , and 23 percent ( P=0.005 ) had improvements in the quality of life . Adverse events were also more common in the groups that received docetaxel . CONCLUSIONS When given with prednisone , treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain , serum PSA level , and quality of life , as compared with mitoxantrone plus prednisone", "CONTEXT Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy , but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival , and if so , the subgroup of men most likely to benefit . OBJECTIVES To quantify the relative improvement in prostate cancer-specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy , and to identify subgroups for whom salvage treatment is most beneficial . DESIGN , SETTING , AND PATIENTS Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982 - 2004 , followed up through December 28 , 2007 , who experienced biochemical and /or local recurrence and received no salvage treatment ( n = 397 ) , salvage radiotherapy alone ( n = 160 ) , or salvage radiotherapy combined with hormonal therapy ( n = 78 ) . MAIN OUTCOME MEASURE Prostate cancer-specific survival defined from time of recurrence until death from disease . RESULTS With a median follow-up of 6 years after recurrence and 9 years after prostatectomy , 116 men ( 18 % ) died from prostate cancer , including 89 ( 22 % ) who received no salvage treatment , 18 ( 11 % ) who received salvage radiotherapy alone , and 9 ( 12 % ) who received salvage radiotherapy and hormonal therapy . Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer-specific survival relative to those who received no salvage treatment ( hazard ratio [ HR ] , 0.32 [ 95 % confidence interval { CI } , 0.19 - 0.54 ] ; P hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer-specific survival ( HR , 0.34 [ 95 % CI , 0.17 - 0.69 ] ; P = .003 ) . The increase in prostate cancer-specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established prognostic factors . Salvage radiotherapy initiated more than 2 years after recurrence provided no significant increase in prostate cancer-specific survival . Men whose prostate-specific antigen level never became undetectable after salvage radiotherapy did not experience a significant increase in prostate cancer-specific survival . Salvage radiotherapy also was associated with a significant increase in overall survival . CONCLUSIONS Salvage radiotherapy administered within 2 years of biochemical recurrence was associated with a significant increase in prostate cancer-specific survival among men with a prostate-specific antigen doubling time of less than 6 months , independent of other prognostic features such as pathological stage or Gleason score . These preliminary findings should be vali date d in other setting s , and ultimately , in a r and omized controlled trial", "OBJECTIVE EORTC trial 30891 compared immediate versus deferred and rogen-deprivation therapy ( ADT ) in T0 - 4 N0 - 2 M0 prostate cancer ( PCa ) . Many patients r and omly assigned to deferred ADT did not require ADT because they died before becoming symptomatic . The question arises whether serum prostate-specific antigen ( PSA ) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment . METHODS PSA data at baseline , PSA doubling time ( PSADT ) in patients receiving no ADT , and time to PSA relapse ( > 2 ng/ml ) in patients whose PSA declined to ADT were analyzed in 939 eligible patients r and omly assigned to immediate ( n=468 ) or deferred ADT ( n=471 ) . RESULTS In both arms , patients with a baseline PSA>50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA risk of PCa death was approximately 7.5-fold higher in patients with PSADT12 mo . Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA , suggesting that baseline PSA may also reflect disease aggressiveness . CONCLUSIONS Patients with a baseline PSA>50 ng/ml and /or a PSADT risk to die from PCa and might have benefited from immediate ADT , whereas patients with a baseline PSA 12 mo ) were likely to die of causes unrelated to PCa , and thus could be spared the burden of immediate ADT", "BACKGROUND Appropriate timing of and rogen deprivation treatment ( ADT ) for prostate cancer is controversial . Our aim was to determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed . METHODS Eligible patients from 36 institutes in the USA were r and omly assigned in 1988 - 93 to receive immediate ADT ( n=47 ) or to be observed ( n=51 ) , with ADT to be given on detection of distant metastases or symptomatic recurrences . Patients were followed up every 3 months for the first year and every 6 months thereafter . The primary endpoint was progression-free survival ; secondary endpoints were overall and disease-specific survival . Analysis was by intention to treat . To ensure that the treatment groups were comparable , we did a retrospective central pathology review of slides and re grade d the Gleason scores for available sample s. This trial pre date s the requirement for clinical trial registration . FINDINGS At median follow-up of 11.9 years ( range 9.7 - 14.5 for surviving patients ) , men assigned immediate ADT had a significant improvement in overall survival ( hazard ratio 1.84 [ 95 % CI 1.01 - 3.35 ] , p=0.04 ) , prostate-cancer-specific survival ( 4.09 [ 1.76 - 9.49 ] , p=0.0004 ) , and progression-free survival ( 3.42 [ 1.96 - 5.98 ] , p ADT , 30 observation ) , 16 were down grade d from the original Gleason score ( between groups or = 8) and five were up grade d. We recorded similar proportions of score changes in each group ( p=0.68 ) , and no difference in score distribution by treatment ( p=0.38 ) . After adjustment for score , associations were still significant between treatment and survival ( overall , p=0.02 ; disease-specific , p=0.002 ; progression-free survival , p ADT benefits patients with nodal metastases who have undergone prostatectomy and lymphadenectomy , compared with those who receive deferred treatment . The beneficial effects of early ADT , rather than an imbalance in risk factors , are likely to explain the differences in outcomes between treatments", "PURPOSE To determine the impact of adjuvant and rogen deprivation therapy ( ADT ) for patients who have node-positive prostate cancer in the prostate-specific antigen ( PSA ) era . PATIENTS AND METHODS We used linked Surveillance , Epidemiology and End Results -Medicare data to construct a cohort of men who underwent radical prostatectomy ( RP ) between 1991 and 1999 and who had positive regional lymph nodes . We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP , and we compared them to the men who had not received adjuvant ADT . We used propensity scores to balance potential confounders of receiving adjuvant ADT ( ie , tumor characteristics , extent of nodal disease , demographics , receipt of radiation therapy ) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival ( OS ) , stratified by propensity score quintile . We conducted a sensitivity analysis that used 90 , 150 , 180 , and 365 days as the definition for adjuvant ADT . RESULTS A total of 731 men were identified , 209 of whom received ADT within 120 days of RP . There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group ( HR , 0.97 ; 95 % CI , 0.71 to 1.27 ) . There was no statistically significant survival difference with 90 , 150 , 180 , and 365 days as the adjuvant ADT definition . CONCLUSION Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival . Because observational studies should be considered hypothesis-generating studies , these results should be vali date d in a prospect i ve fashion in a similar patient population", "A Second Act for Anti and rogens Men with advanced prostate cancer are often treated with anti and rogens ; drugs that inhibit the activity of male hormones , such as testosterone , that help drive tumor growth . Many of these drugs act by functionally disrupting the and rogen receptor ( AR ) , a transcriptional regulator of cell proliferation , but tumors eventually become resistant to the drugs by expressing higher levels of the AR . Tran et al. ( p. 787 , published online 9 April ) have developed a “ second-generation ” anti and rogen , a thiohydantoin called MDV3100 , which binds the AR with high affinity . MDV3100 retains its anticancer activity in cell culture and in mouse models even when AR levels are elevated . The drug appears to act both by inhibiting translocation of the AR into the nucleus and by reducing its transcriptional activity . MDV3100 is being tested in patients with advanced prostate cancer , the first group of which have shown a decline in blood levels of a marker of cancer growth , prostate-specific antigen . A drug that binds to the and rogen receptor acts by disrupting its activity in the cell nucleus . Metastatic prostate cancer is treated with drugs that antagonize and rogen action , but most patients progress to a more aggressive form of the disease called castration-resistant prostate cancer , driven by elevated expression of the and rogen receptor . Here we characterize the diarylthiohydantoins RD162 and MDV3100 , two compounds optimized from a screen for nonsteroidal anti and rogens that retain activity in the setting of increased and rogen receptor expression . Both compounds bind to the and rogen receptor with greater relative affinity than the clinical ly used anti and rogen bicalutamide , reduce the efficiency of its nuclear translocation , and impair both DNA binding to and rogen response elements and recruitment of coactivators . RD162 and MDV3100 are orally available and induce tumor regression in mouse models of castration-resistant human prostate cancer . Of the first 30 patients treated with MDV3100 in a Phase I/II clinical trial , 13 of 30 ( 43 % ) showed sustained declines ( by > 50 % ) in serum concentrations of prostate-specific antigen , a biomarker of prostate cancer . These compounds thus appear to be promising c and i date s for treatment of advanced prostate cancer", "PURPOSE Hormonal therapy ( HT ) is the current mainstay of systemic treatment for prostate specific antigen ( PSA ) only recurrence ( PSAR ) , however , there is virtually no published literature comparing HT to observation in the clinical setting . The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational data base to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach . MATERIAL S AND METHODS Of 5,382 men in the data base who underwent primary radical prostatectomy ( RP ) , 4,967 patients were treated in the PSA-era between 1988 and December 2002 . Of those patients 1,352 men who had PSAR ( PSA after surgery greater than 0.2 ng/ml ) and had postoperative followup greater than 6 months were used as the study cohort . These patients were further divided into an early HT group in which patients ( 355 ) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients ( 997 ) who received no HT before clinical metastasis or by current followup . The primary end point was the development of clinical metastases . Of the 1,352 patients with PSAR clinical metastases developed in 103 ( 7.6 % ) . Patients were also stratified by surgical Gleason sum , PSA doubling time and timing of recurrence . Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome . RESULTS Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less ( Hazards ratio = 2.12 , p = 0.01 ) . However , in the overall cohort early HT did not impact clinical metastases . Race , age at RP and PSA at diagnosis had no effect on metastasis-free survival ( p > 0.05 ) . CONCLUSIONS The retrospective observational multicenter data base analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup . Further study with longer followup and r and omized trials are needed to address this important issue", "PURPOSE This was an exploratory analysis of a trial of intermittent and rogen deprivation ( IAD ) in men with biochemical relapse ( BR ) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer ( CRPC ) and death . PATIENTS AND METHODS Men with BR of prostate cancer after radical prostatectomy ( RP ) or radiation ( RT ) were treated with and rogen deprivation therapy ( ADT ) comprised of leuprolide and flutamide . After 9 months on treatment , ADT was stopped , and monthly prostate-specific antigen ( PSA ) levels were observed during the off-treatment interval . When the PSA reached a threshold value ( 1 ng/mL for RP , 4 ng/mL for RT ) , ADT was resumed in a new cycle . Patients were treated intermittently in this manner until CRPC , which was defined as > or = two consecutive increasing PSA values while on ADT with castrate testosterone levels . RESULTS Seventy-two of 100 patients enrolled onto the study met criteria for this analysis . The duration of the first off-treatment interval ( 40 weeks ) was associated with shorter time to CRPC ( hazard ratio = 2.9 ; 95 % CI , 1.1 to 7.7 ; P = .03 ) and death ( hazard ratio = 3.8 ; 95 % CI , 1.1 to 13.6 ; P = .04 ) after adjusting for age , stage , grade , and PSA at diagnosis . CONCLUSION In patients who completed the first cycle of IAD , a duration of the first off-treatment interval of < or = 40 weeks defines a subset of patients at higher risk of CRPC and death . Conversely , patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis", "The aim of this study was to compare the efficacy of total intermittent and rogen deprivation ( IAD ) versus total continuous and rogen deprivation ( CAD ) for treating patients with advanced prostate cancer in a phase III r and omized trial . A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were r and omized to receive combined and rogen blockade according to a continuous ( n = 33 ) or intermittent ( n = 35 ) regimen . Therapeutic monitoring was assessed by use of serum prostate-specific antigen ( PSA ) measurements . Patients in the CAD and IAD groups were equally stratified for age , biopsy Gleason score , and baseline serum PSA levels . The outcome variable was time to and rogen-independence of the tumor , which was defined as increasing serum PSA levels despite and rogen blockade . Mean follow-up was 30.8 months . The 35 IAD-treated patients completed 91 cycles , and 19 of them ( 54.3 % ) completed > or = 3 cycles . Median cycle length and percentage of time off therapy were 9.0 months and 59.5 , respectively . The estimated 3-year progression rate was significantly lower in the IAD group ( 7.0 % + /- 4.8 % ) than in the CAD group ( 38.9 % + /- 11.2 % , P = 0.0052 ) . Our data suggest that IAD treatment may maintain the and rogen-dependent state of advanced human prostate cancer , as assessed by PSA measurements , at least as long as CAD treatment . Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival", "PURPOSE We investigated the efficacy and safety of degarelix treatment and the effects of switching from leuprolide to degarelix in an ongoing extension study with a median 27.5-month followup of a pivotal 1-year prostate cancer trial . MATERIAL S AND METHODS Patients who completed a 1-year pivotal phase III trial continued on the same monthly degarelix maintenance dose ( 160 or 80 mg in 125 each ) , or were re-r and omized from leuprolide 7.5 mg to degarelix 240/80 mg ( 69 ) or 240/160 mg ( 65 ) . Data are shown on the approved degarelix 240/80 mg dose . The primary end point was safety/tolerability and the secondary end points were testosterone , prostate specific antigen , luteinizing hormone and follicle-stimulating hormone responses , and prostate specific antigen failure and progression-free survival . RESULTS During followup testosterone and prostate specific antigen suppression were similar to those in the 1-year trial in patients who continued on degarelix or switched from leuprolide . The prostate specific antigen progression-free survival hazard rate was decreased significantly after the switch in the leuprolide/degarelix group while the rate in those who continued on degarelix was consistent with the rate in treatment year 1 . The same hazard rate change pattern occurred in the group with baseline prostate specific antigen greater than 20 ng/ml . Adverse event frequency was similar between the groups and decreased with time . CONCLUSIONS Data support the statistically significant prostate specific antigen progression-free survival benefit for degarelix over leuprolide seen during year 1 and the use of degarelix as first line and rogen deprivation therapy as an alternative to a gonadotropin-releasing hormone agonist", "BACKGROUND Recent data suggest prostate-specific antigen ( PSA ) progression may predict overall survival in prostate cancer patients . OBJECTIVE To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival . DESIGN , SETTING , AND PARTICIPANTS Phase 3 , 1-yr , multicentre , r and omised , open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo , and then 80 mg monthly ( 240/80 mg ) ; degarelix at 240 mg for 1 mo , and then 160 mg monthly ; and leuprolide at 7.5 mg/mo . Overall , 610 patients with histologically confirmed prostate cancer ( all stages ) , for whom and rogen deprivation therapy was indicated , were included . The primary end point of this trial has been reported previously ; the protocol led and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg ( dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer ) . MEASUREMENTS PSA progression-free survival ( two consecutive increases in PSA of 50 % compared with nadir and ≥ 5 ng/ml on two consecutive measurements at least 2 wk apart or death ) and change in PSA were review ed . Effects of baseline disease stage ( localised , locally advanced , and metastatic ) and PSA level ( 20 - 50 , and > 50 ng/ml ) were analysed . RESULTS AND LIMITATIONS Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide ( p=0.05 ) . PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA > 20 ng/ml . Patients with PSA > 20 ng/ml had a significantly longer time to PSA recurrence with degarelix ( p=0.04 ) . The relatively low number of patients in each subgroup is a limitation of this study . CONCLUSIONS These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide . PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study . Further studies are warranted to confirm these findings" ]	41182cfa-06ff-11f0-808a-c43d1ab1c353
We read with great interest the article by Zuccotti et al. about the possibility of implementing a primary prevention strategy for allergic diseases ( 1 ) . This article is conceptually linked to the EAACI Food Allergy and Anaphylaxis Guidelines recommendations ( 2 ) that stated ‘ there is no evidence to recommend that breastfeeding women should modify their diet or take any supplements such as probiotics in order to prevent food allergy in their children ’ and during infancy that ‘ there is no evidence to recommend prebiotics or probiotics or other dietary supplements based on particular nutrients to prevent food allergy ’ . It is also linked to the recently published WAO guidelines ( 3 ) which are partially conflicting with the previous conclusion because it suggests that ‘ using probiotics in women who breastfeed infants at high risk of developing allergy , because considering all critical outcomes , there is a net benefit result ing primarily from prevention of eczema ( conditional recommendation , very low quality evidence ) ’ . We have already commented the above-mentioned discrepancies by supporting the lack of evidence to indicate the use of probiotics in the primary prevention of atopic eczema ( 4 , 5 ) . This systematic review and meta- analysis ( 1 ) substantially examine the same patients . The authors describe a significant effect of probiotic supplementation in the reduction of the relative risk for eczema in infants and conclude that ‘ the prevention of infantile eczema represents a potential indication for probiotic use during pregnancy and early infancy ’ ( 1 ) . In our opinion , two method ological points determining the bias of the results are question able . The first point is the inclusion of the same patients at different phases of follow-up in the statistical analysis . In particular , the study conducted by Rautawa et al. ( 6 ) was a part of a double-blind , placebo-controlled trial performed by Kalliomaki et al. ( 7 ) ; the study by Prescott et al. ( 8) represents a follow-up of the same infants recruited and described by Taylor et al. ( 9 ) . Furthermore , Abrahamsson et al. ( 10 ) showed results after a 7-year follow-up of infants from a previous r and omized double-blind placebo-controlled trial published in 2007 ( 11 ) ; part of immunological and clinical data of the same infants are also reported in the article by Bottcher et al. ( 12 ) . Wickens et al. showed in three different articles the outcomes at 2 , 4 and 6 years of the same children ( 13–15 ) . In case of more than one publication or more than one follow-up of the same population , we believe that only data from one study for a specific item ( eczema ) should be considered and included in a correct statistical analysis . The second point to highlight is the heterogeneity of the probiotics used , as also the WAO guidelines ( 3 ) observed . For example , the analysis of a subgroup of patients named ‘ sub-meta- analysis ’ showed significant effect of probiotic ‘ mixtures ’ supplementation in the prevention of eczema ( RR 0.54 [ 95 % CI : 0.43–0.68 ] , P Probiotic mixtures used in these studies were all different ( Table 1 ) . As	[ "The immunological composition of breast milk differs between mothers . The reasons for these differences and the consequences for the breast-fed infants are poorly understood . The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies . Total IgA , secretory IgA ( SIgA ) , TGF-beta1 , TGF-beta2 , IL-10 , TNF , soluble CD14 ( sCD14 ) , and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri ( n = 54 ) or placebo ( n = 55 ) from gestational week 36 until delivery . Bacteriological analyses of L. reuteri were performed in faecal sample s of the mothers . The infants were followed prospect ively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and /or circulating allergen-specific IgE antibodies at 6 , 12 , and 24 months of age . Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum . For TGF-beta2 , this association was most pronounced in mothers with detectable L. reuteri in faeces . Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life . A similar trend was observed for development of IgE-associated eczema . The levels of total IgA , SIgA , TGF-beta1 , TNF , sCD14 , and Na/K ratios in breast milk were not affected by the intake of L. reuteri . None of these parameters correlated with sensitization or development of eczema in the infant , except for high Na/K ratios that associated with increased risk of sensitization . Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2 , and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants", "BACKGROUND Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies . In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life . Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora . We assessed the effect on atopic disease of Lactobacillus GG ( which is safe at an early age and effective in treatment of allergic inflammation and food allergy ) . METHODS In a double-blind , r and omised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative ( or partner ) with atopic eczema , allergic rhinitis , or asthma , and postnatally for 6 months to their infants . Chronic recurring atopic eczema , which is the main sign of atopic disease in the first years of life , was the primary endpoint . FINDINGS Atopic eczema was diagnosed in 46 of 132 ( 35 % ) children aged 2 years . Asthma was diagnosed in six of these children and allergic rhinitis in one . The frequency of atopic eczema in the probiotic group was half that of the placebo group ( 15/64 [ 23 % ] vs 31/68 [ 46 % ] ; relative risk 0.51 [ 95 % CI 0.32 - 0.84 ] ) . The number needed to treat was 4.5 ( 95 % CI 2.6 - 15.6 ) . INTERPRETATIONS Lactobacillus GG was effective in prevention of early atopic disease in children at high risk . Thus , gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics , for prevention of atopic disease", "Controversy exists regarding the preventive effect of probiotics on the development of eczema or atopic dermatitis . We investigated whether supplementation of probiotics prevents the development of eczema in infants at high risk . In a r and omized , double-blind , placebo-controlled trial , 112 pregnant women with a family history of allergic diseases received a once-daily supplement , either a mixture of Bifidobacterium bifidum BGN4 , B. lactis AD011 , and Lactobacillus acidophilus AD031 , or placebo , starting at 4 - 8 wks before delivery and continuing until 6 months after delivery . Infants were exclusively breast-fed during the first 3 months , and were subsequently fed with breastmilk or cow 's milk formula from 4 to 6 months of age . Clinical symptoms of the infants were monitored until 1 yr of age , when the total and specific IgE against common food allergens were measured . A total of 68 infants completed the study . The prevalence of eczema at 1 yr in the probiotic group was significantly lower than in the placebo group ( 18.2 % vs. 40.0 % , p=0.048 ) . The cumulative incidence of eczema during the first 12 months was reduced significantly in probiotic group ( 36.4 % vs. 62.9 % , p=0.029 ) ; however , there was no difference in serum total IgE level or the sensitization against food allergens between the two groups . Prenatal and postnatal supplementation with a mixture of B. bifidum BGN4 , B. lactis AD011 , and L. acidophilus AD031 is an effective approach in preventing the development of eczema in infants at high risk of allergy during the first year of life", "Using a double blind r and omized placebo‐controlled trial ( Australian New Zeal and Clinical Trials Registry : ACTRN12607000518460 ) , we have shown that in a high risk birth cohort , maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation until 2 years with Lactobacillus rhamnosus HN001 ( HN001 ) ( 6 × 109 cfu/day ) halved the cumulative prevalence of eczema by age 2 years . Bifidobacterium animalis subsp lactis HN019 ( HN019 ) ( 9 × 109 cfu/day ) had no effect", "BACKGROUND An altered microbial exposure may underlie the increase of allergic diseases in affluent societies . Probiotics may alleviate and even prevent eczema in infants . OBJECTIVE To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri . METHODS Double-blind , r and omized , placebo-controlled trial , which comprised 232 families with allergic disease , of whom 188 completed the study . The mothers received L reuteri ATCC 55730 ( 1 x 10(8 ) colony forming units ) daily from gestational week 36 until delivery . Their babies then continued with the same product from birth until 12 months of age and were followed up for another year . Primary outcome was allergic disease , with or without positive skin prick test or circulating IgE to food allergens . RESULTS The cumulative incidence of eczema was similar , 36 % in the treated versus 34 % in the placebo group . The L reuteri group had less IgE-associated eczema during the second year , 8 % versus 20 % ( P = .02 ) , however . Skin prick test reactivity was also less common in the treated than in the placebo group , significantly so for infants with mothers with allergies , 14 % versus 31 % ( P = .02 ) . Wheeze and other potentially allergic diseases were not affected . CONCLUSION Although a preventive effect of probiotics on infant eczema was not confirmed , the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease . CLINICAL IMPLICATION Probiotics may reduce the incidence of IgE-associated eczema in infancy", "BACKGROUND The role of probiotics in prevention of allergic disease is still not clearly established , although early reports suggested Lactobacillus GG halved the risk of eczema at 2 years . OBJECTIVE To determine whether probiotic supplementation in early life could prevent development of eczema and atopy at 2 years . METHODS Double-blind , r and omized placebo-controlled trial of infants at risk of allergic disease . Pregnant women were r and omized to take Lactobacillus rhamnosus HN001 ( L rhamnosus ) , Bifidobacterium animalis subsp lactis strain HN019 or placebo daily from 35 weeks gestation until 6 months if breast-feeding , and their infants were r and omized to receive the same treatment from birth to 2 years ( n = 474 ) . The infant 's cumulative prevalence of eczema and point prevalence of atopy , using skin prick tests to common allergens , was assessed at 2 years . RESULTS Infants receiving L rhamnosus had a significantly ( P = .01 ) reduced risk of eczema ( hazard ratio [ HR ] , 0.51 ; 95 % CI , 0.30 - 0.85 ) compared with placebo , but this was not the case for B animalis subsp lactis ( HR , 0.90 ; 95 % CI , 0.58 - 1.41 ) . There was no significant effect of L rhamnosus ( HR , 0.74 ; 95 % CI , 0.46 - 1.18 ) or B animalis subsp lactis ( HR , 0.82 ; 95 % CI , 0.52 - 1.28 ) on atopy . L rhamnosus ( 71.5 % ) was more likely than B animalis subsp lactis ( 22.6 % ) to be present in the feces at 3 months , although detection rates were similar by 24 months . CONCLUSION We found that supplementation with L rhamnosus , but not B animalis subsp lactis , substantially reduced the cumulative prevalence of eczema , but not atopy , by 2 years . Underst and ing how Lactobacilli act to prevent eczema requires further investigation", "BACKGROUND Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy . This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age . OBJECTIVE To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects . METHODS A r and omized , placebo-controlled trial with oral supplementation with L. reuteri ATCC 55730 ( 1 × 10(8 ) CFU ) during the last month of gestation and through the first year of life comprising 232 families with allergic disease , of whom 184 completed a 7-yr follow-up . The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity ( Clinical Trials.gov ID NCT01285830 ) . RESULTS The prevalence of asthma ( 15 % in the probiotic vs. 16 % in placebo group ) , allergic rhinoconjunctivitis ( 27 % vs. 20 % ) , eczema ( 21 % vs. 19 % ) and skin prick test reactivity ( 29 % vs. 26 % ) was similar in the probiotic and placebo group . Growth indices and gastrointestinal symptoms were similar in the two groups . No severe adverse events were reported . CONCLUSION The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age . Thus , the effect of L. reuteri on the immune system seems to be transient . Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects", "The prevalence of atopic diseases is increasing throughout the Western world , and means of primary prevention are needed to reverse this trend . The role of breast-feeding , the best source of infant nutrition , in protection against atopic disease remains elusive . In this double-blinded , placebo-controlled study of 62 mother-infant pairs , it is shown that administering probiotics to the pregnant and lactating mother increased the immunoprotective potential of breast milk , as assessed by the amount of anti-inflammatory transforming growth factor beta2 ( TGF-beta2 ) in the milk ( 2885 pg/mL [ 95 % CI , 1624 - 4146 ] in mothers receiving probiotics vs 1340 pg/mL [ 95 % CI , 978 - 1702 ] in mothers receiving placebo ; P = .018 ) . The risk of developing atopic eczema during the first 2 years of life in infants whose mothers received probiotics was significantly reduced in comparison with that in infants whose mothers received placebo ( 15 % and 47 % , respectively ; relative risk , 0.32 [ 95 % CI , 0.12 - 0.85 ] ; P = .0098 ) . Maternal atopy was a clear risk factor for atopic eczema in the infant . The infants most likely to benefit from maternal probiotic supplementation were those with an elevated cord blood IgE concentration . Administering probiotics during pregnancy and breast-feeding thus offers a safe and effective mode of promoting the immunoprotective potential of breast-feeding and provides protection against atopic eczema during the first 2 years of life", "Background Prevalence of allergic diseases in infants , whose parents and siblings do not have allergy , is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative . Intestinal microbiota may modulate immunologic and inflammatory systemic responses and , thus , influence development of sensitization and allergy . Probiotics have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention . Objective The World Allergy Organization ( WAO ) convened a guideline panel to develop evidence -based recommendations about the use of probiotics in the prevention of allergy . Methods We identified the most relevant clinical questions and performed a systematic review of r and omized controlled trials of probiotics for the prevention of allergy . We followed the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to develop recommendations . We search ed for and review ed the evidence about health effects , patient values and preferences , and re source use ( up to November 2014 ) . We followed the GRADE evidence -to-decision framework to develop recommendations . Results Currently available evidence does not indicate that probiotic supplementation reduces the risk of developing allergy in children . However , considering all critical outcomes in this context , the WAO guideline panel determined that there is a likely net benefit from using probiotics result ing primarily from prevention of eczema . The WAO guideline panel suggests : a ) using probiotics in pregnant women at high risk for having an allergic child ; b ) using probiotics in women who breastfeed infants at high risk of developing allergy ; and c ) using probiotics in infants at high risk of developing allergy . All recommendations are conditional and supported by very low quality evidence . Conclusions WAO recommendations about probiotic supplementation for prevention of allergy are intended to support parents , clinicians and other health care professionals in their decisions whether to use probiotics in pregnancy and during breastfeeding , and whether to give them to infants", "The role of probiotics in prevention of allergic disease is still not clear ; efficacy may depend on the timing , dose , duration , and specific probiotic used . Using a double‐blind r and omized placebo‐controlled trial ( Australian New Zeal and Clinical Trials Registry : ACTRN12607000518460 ) , we have shown that in a high‐risk birth cohort , maternal supplementation from 35 weeks gestation until 6 months if breastfeeding and infant supplementation from birth until 2 years with Lactobacillus rhamnosus HN001 ( HN001 ) ( 6 × 109 cfu/day ) halved the cumulative prevalence of eczema at 2 and 4 years . Bifidobacterium animalis subsp lactis HN019 ( HN019 ) ( 9 × 109 cfu/day ) had no significant effect " ]	41182d72-06ff-11f0-808a-c43d1ab1c353
Abstract Introduction A Task Force was commissioned jointly by the European Academy of Allergy and Clinical Immunology ( EAACI ) and the Respiratory Effectiveness Group ( REG ) to develop a quality assessment tool for real-life observational research to identify high- quality real-life asthma studies that could be considered within future guideline development . Methods The result ing REal Life EVidence AssessmeNt Tool ( RELEVANT ) was achieved through an extensive analysis of existing initiatives in this area . The first version was piloted among 9 raters across 6 articles ; the revised , interim , version underwent extensive testing by 22 review ers from the EAACI membership and REG collaborator group , leading to further revisions and tool finalisation . RELEVANT was vali date d through an analysis of real-life effectiveness studies identified via systematic review of Medline and Embase data bases and relating to topics for which real-life studies may offer valuable evidence complementary to that from r and omised controlled trials . The topics were selected through a vote among Task Force members and related to the influence of adherence , smoking , inhaler device and particle size on asthma treatment effectiveness . Results Although highlighting a general lack of high- quality real-life effectiveness observational research on these clinical ly important topics , the analysis provided insights into how identified observational studies might inform asthma guidelines developers and clinicians . Overall , RELEVANT appeared reliable and easy to use by expert review ers . Conclusions Using such quality appraisal tools is m and atory to assess whether specific observational real-life effectiveness studies can be used to inform guideline development and /or decision-making in clinical practice	[ "The incidence of asthma has been positively associated with obesity . Asthma comprises diverse “ phenotypes ” reflecting heterogeneity in a number of characteristics , including response to therapy . The present authors examined whether body mass index ( BMI ) influenced the response to placebo , as well as to two asthma controller medications . A post hoc analysis was performed , pooling data from four double-blind , placebo-controlled studies r and omising 3,073 moderate asthmatic adults to montelukast ( n = 1,439 ) , beclomethasone ( n = 894 ) or placebo ( n = 740 ) . The primary end point was asthma control days ; other end points were forced expiratory volume in one second , β-agonist use and nocturnal awakening . Analyses were conducted using BMI classification into normal ( The placebo response for all end points was generally lower with increasing BMI . Similarly , the response to the inhaled corticosteroid decreased , whereas the response to the leukotriene antagonist remained stable . In conclusion , post hoc data from the present study suggested that body mass index may influence the natural history of asthma control ( as reflected by response to placebo ) and may differentially influence response to the two active agents , warranting explicit testing in future prospect i ve studies", "Background : Asthma is a heterogeneous disease with a wide range of clinical phenotypes , not all of which may be encompassed in the subjects included in r and omised controlled trials ( RCTs ) . This makes it difficult for clinicians to know to what extent the evidence derived from RCTs applies to a given patient . Aim : To calculate the proportion of individuals with asthma who would have been eligible for the major asthma RCTs from the data of a r and om community survey of respiratory health . Methods : A postal survey was sent to 3500 r and omly selected individuals aged 25–75 years . Respondents were invited to complete a detailed respiratory question naire and pulmonary function testing . Participants with current asthma were assessed against the eligibility criteria of the 17 major asthma RCTs cited in the Global Initiative for Asthma ( GINA ) guidelines . Findings : A total of 749 participants completed the full survey , of whom 179 had current asthma . A median 4 % of participants with current asthma ( range 0–36 % ) met the eligibility criteria for the included RCTs . A median 6 % ( range 0–43 % ) of participants with current asthma on treatment met the eligibility criteria . Interpretation : This study shows that the major asthma RCTs on which the GINA guidelines are based may have limited external validity as they have been performed on highly selected patient population s. Most of the participants with current asthma on treatment in the community would not have been eligible for these RCTs ", "BACKGROUND Most r and omized trials of treatment for asthma study highly selected patients under idealized conditions . METHODS We conducted two parallel , multicenter , pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist ( LTRA ) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist ( LABA ) as add-on therapy in patients already receiving inhaled glucocorticoid therapy . Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life ( Mini Asthma Quality of Life Question naire [ MiniAQLQ ] score ≤6 ) or inadequate asthma control ( Asthma Control Question naire [ ACQ ] score ≥1 ) . We r and omly assigned patients to 2 years of open-label therapy , under the care of their usual physician , with LTRA ( 148 patients ) or an inhaled glucocorticoid ( 158 patients ) in the first-line controller therapy trial and LTRA ( 170 patients ) or LABA ( 182 patients ) added to an inhaled glucocorticoid in the add-on therapy trial . RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials . At 2 months , differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence ( 95 % confidence interval [ CI ] for an adjusted mean difference , -0.3 to 0.3 ) . At 2 years , mean MiniAQLQ scores approached equivalence , with an adjusted mean difference between treatment groups of -0.11 ( 95 % CI , -0.35 to 0.13 ) in the first-line controller therapy trial and of -0.11 ( 95 % CI , -0.32 to 0.11 ) in the add-on therapy trial . Exacerbation rates and ACQ scores did not differ significantly between the two groups . CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients . Equivalence was not proved at 2 years . The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group . ( Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others ; Controlled Clinical Trials number , IS RCT N99132811 . )", "OBJECTIVES Most contemporary epidemiologic studies require complex analytical methods to adjust for bias and confounding . New methods are constantly being developed , and older more established methods are yet appropriate . Careful application of statistical analysis techniques can improve causal inference of comparative treatment effects from nonr and omized studies using secondary data bases . A Task Force was formed to offer a review of the more recent developments in statistical control of confounding . METHODS The Task Force was commissioned and a chair was selected by the ISPOR Board of Directors in October 2007 . This Report , the third in this issue of the journal , addressed methods to improve causal inference of treatment effects for nonr and omized studies . RESULTS The Task Force Report recommends general analytic techniques and specific best practice s where consensus is reached including : use of stratification analysis before multivariable modeling , multivariable regression including model performance and diagnostic testing , propensity scoring , instrumental variable , and structural modeling techniques including marginal structural models , where appropriate for secondary data . Sensitivity analyses and discussion of extent of residual confounding are discussed . CONCLUSIONS Valid findings of causal therapeutic benefits can be produced from nonr and omized studies using an array of state-of-the-art analytic techniques . Improving the quality and uniformity of these studies will improve the value to patients , physicians , and policymakers worldwide", "Observational studies and pragmatic trials can complement classical r and omized controlled trials ( RCTs ) by providing data more relevant to the circumstances under which medicine is routinely practice d , thereby providing practical guidance for clinicians . The bearing of RCT findings on day-to-day practice can be weighted and the data more meaningfully interpreted by practicing clinicians if evidence is integrated from a variety of different study design s and method ologies . The advent of observational studies and pragmatic trials , often referred to as \" real-life studies , \" has met with a degree of cynicism , but their role and value is gaining widespread recognition and support among clinicians . This article discusses where observational studies and pragmatic trials have utility , namely : in addressing clinical questions that are unanswered and /or unanswerable by RCTs ; in testing new hypotheses and possible license extensions ; and in helping to differentiate between available therapies for a given indication . Moreover , it seeks to highlight how the different approaches fit within a conceptual framework of evidence relevant to clinical practice , a step-change in the traditional view of medical evidence", "Objectives The study aim ed at prospect ively evaluating the evolution of asthma control in Italy , to evaluate the reasons for lack of asthma control , perceived quality of life ( QoL ) and association with level of asthma control , the impact of pharmacological treatment , the number of exacerbations and the healthcare re source consumption . Methods PRISMA ( PRospect I ve Study on asthMA control ) was an observational study performed in asthmatic patients including a cross-sectional phase and a 12-month prospect i ve phase . Asthma control was assessed with the Asthma Control Test ™ ( ACT ) and QoL was evaluated with EuroQoL-5D question naire filled in and collected during 5 clinic visits together with all the other data . Results The prospect i ve phase included 1017 patients with uncontrolled ( 55.7 % ) or partly controlled asthma ( 44.3 % ) . Out of the 739 patients evaluable after 12 months , 22.2 % achieved full asthma control ( ACT score = 25 ) and 58.7 % reached a good control ( ACT score : 20–24 ) . The improvement in asthma control was associated with improved QoL and reduced hospital visits . The main reasons for lack of asthma control were comorbidities , continued exposure to irritants/triggers and poor adherence to therapy . The frequency of exacerbations was lower in patients with controlled asthma . A fixed combination therapy with an inhaled corticosteroid and a long-acting β2 agonist was reported by 77.0 % of patients . A better asthma control and improved QoL were achieved with extrafine beclomethasone/formoterol compared to either budesonide/formoterol or fluticasone/salmeterol . Conclusions An improvement in asthma control and QoL can be achieved during a 1-year monitoring in a real life setting . Extrafine beclomethasone/formoterol was associated with significant benefit in terms of asthma control and QoL compared to large-particles combinations . Clinical Trials.gov number NCT01110460", "Purpose : Results of r and omized controlled trials may not predict effectiveness of inhaled corticosteroids ( ICS ) in real-world clinical practice , where inhaler technique and device characteristics can influence effectiveness . We compared asthma outcomes for ICS delivered via three different inhaler devices : pressurized metered-dose inhaler ( pMDI ) , breath-actuated MDI ( BAI ) , and dry powder inhaler ( DPI ) . Patients and methods : This retrospective data base study evaluated 1-year outcomes for primary care patients with asthma aged 5–60 years prescribed their first ICS ( initiation population ) by pMDI ( n = 39,746 ) , BAI ( n = 9809 ) , or DPI ( n = 6792 ) , or their first ICS dose increase ( step-up population ) by pMDI ( n = 6245 ) , BAI ( n = 1388 ) , or DPI ( n = 1536 ) . Co- primary outcome measures were composite proxy measures of asthma control ( no hospital attendance for asthma , oral corticosteroids , or antibiotics for lower respiratory infection ) and severe exacerbations ( unscheduled hospital admission , emergency room attendance , or oral corticosteroids ) . Outcomes were adjusted for potential confounding factors identified during a baseline year . Results : In the initiation population , adjusted odds ratios ( 95 % confidence intervals [ CI ] ) for asthma control , as compared with pMDIs , were significantly better for BAIs ( 1.08 [ 1.02–1.14 ] ) and DPIs ( 1.13 [ 1.06–1.21 ] ) , while adjusted exacerbation rate ratios ( 95 % CI ) were 1.00 ( 0.93–1.08 ) and 0.88 ( 0.81–0.95 ) , respectively . In the step-up population , adjusted odds of asthma control were 1.21 ( 1.05–1.39 ) for BAIs and 1.13 ( 0.99–1.29 ) for DPIs ; adjusted exacerbation rate ratios were 0.83 ( 0.71–0.98 ) for BAIs and 0.85 ( 0.74–0.98 ) for DPIs , compared with pMDIs . Conclusion : Inhaler device selection may have a bearing on clinical outcomes . Differences in real-world effectiveness among these devices require closer evaluation in well- design ed prospect i ve trials", "Background The CONSORT statement is intended to improve reporting of r and omised controlled trials and focuses on minimising the risk of bias ( internal validity ) . The applicability of a trial ’s results ( generalisability or external validity ) is also important , particularly for pragmatic trials . A pragmatic trial ( a term first used in 1967 by Schwartz and Lellouch ) can be broadly defined as a r and omised controlled trial whose purpose is to inform decisions about practice . This extension of the CONSORT statement is intended to improve the reporting of such trials and focuses on applicability . Methods At two , two-day meetings held in Toronto in 2005 and 2008 , we review ed the CONSORT statement and its extensions , the literature on pragmatic trials and applicability , and our experiences in conducting pragmatic trials . Recommendations We recommend extending eight CONSORT checklist items for reporting of pragmatic trials : the background , participants , interventions , outcomes , sample size , blinding , participant flow , and generalisability of the findings . These extensions are presented , along with illustrative examples of reporting , and an explanation of each extension . Adherence to these reporting criteria will make it easier for decision makers to judge how applicable the results of r and omised controlled trials are to their own conditions . Empirical studies are needed to ascertain the usefulness and comprehensiveness of these CONSORT checklist item extensions . In the meantime we recommend that those who support , conduct , and report pragmatic trials should use this extension of the CONSORT statement to facilitate the use of trial results in decisions about health care . Pragmatic trials are design ed to inform decisions about practice , but poor reporting can reduce their usefulness . The CONSORT and Practihc groups describe modifications to the CONSORT guidelines to help readers assess the applicability of the", "BACKGROUND Because r and omized controlled trials of established pediatric asthma therapies are expensive and difficult to perform , observational studies may fill gaps in the evidence base . OBJECTIVES To compare the effectiveness of representative small-particle inhaled corticosteroid ( ICS ) with that of st and ard size-particle ICS for children initiating or stepping up ICS therapy for asthma ( analysis 1 ) and to compare the effectiveness of ICS dose step-up using small-particle ICS with adding long-acting β2-agonist ( LABA ) to the ICS ( analysis 2 ) . METHODS These historical matched cohort analyses drew on electronic medical records of children with asthma aged 5 to 11 years . Variables measured during 2 consecutive years ( 1 baseline year for confounder definition and 1 outcome year ) included risk-domain asthma control ( no hospital attendance for asthma , acute oral corticosteroids , or lower respiratory tract infection requiring antibiotics ) and rate of severe exacerbations ( asthma-related emergency , hospitalization , or oral corticosteroids ) . RESULTS In the initiation population ( n = 797 in each cohort ) , children prescribed small-particle ICS versus st and ard size-particle ICS experienced greater odds of asthma control ( adjusted odds ratio , 1.49 ; 95 % CI , 1.10 - 2.02 ) and lower severe exacerbation rate ( adjusted rate ratio , 0.56 ; 95 % CI , 0.35 - 0.88 ) . Step-up outcomes ( n = 206 in each cohort ) were also significantly better for small-particle ICS , with asthma control adjusted odds ratio of 2.22 ( 95 % CI , 1.23 - 4.03 ) and exacerbations adjusted rate ratio of 0.49 ( 95 % CI , 0.27 - 0.89 ) . The number needed to treat with small-particle ICS to achieve 1 additional child with asthma control was 17 ( 95 % CI , 9 - 107 ) for the initiation population and 5 ( 95 % CI , 3 - 78 ) for the step-up population . Outcomes were not significantly different for stepped-up small-particle ICS dose versus ICS/LABA combination ( n = 185 in each cohort ) . CONCLUSIONS Initiating or stepping up the ICS dose with small-particle ICS rather than with st and ard size-particle ICS is more effective and shows similar effectiveness to add-on LABA in childhood asthma", "RATIONALE Aerosol particle size influences the extent , distribution , and site of inhaled drug deposition within the airways . OBJECTIVES We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery . METHODS In a r and omized , double-blind , placebo-controlled study , 12 subjects with asthma ( FEV1 , 76.8 + /- 11.4 % predicted ) inhaled technetium-99m-labeled monodisperse albuterol aerosols ( 30-microg dose ) of 1.5- , 3- , and 6-microm mass median aerodynamic diameter , at slow ( 30 - 60 L/min ) and fast ( > 60 L/min ) inspiratory flows . Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy . Pulmonary function and tolerability measurements were simultaneously assessed . Clinical efficacy was also compared with unlabeled monodisperse albuterol ( 15-microg dose ) and 200 microg metered-dose inhaler ( MDI ) albuterol . RESULTS Smaller particles achieved greater total lung deposition ( 1.5 microm [ 56 % ] , 3 microm [ 50 % ] , and 6 microm [ 46 % ] ) , farther distal airways penetration ( 0.79 , 0.60 , and 0.36 , respective penetration index ) , and more peripheral lung deposition ( 25 , 17 , and 10 % , respectively ) . However , larger particles ( 30-microg dose ) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol ( deltaFEV1 [ ml ] : 6 microm [ 551 ] , 3 microm [ 457 ] , 1.5 microm [ 347 ] , MDI [ 494 ] ) . Small particles were exhaled more ( 1.5 microm [ 22 % ] , 3 microm [ 8 % ] , 6 microm [ 2 % ] ) , whereas greater oropharyngeal deposition occurred with large particles ( 15 , 31 , and 43 % , respectively ) . Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles , with less bronchodilation . A shift in aerosol distribution to the proximal airways was observed for all particles . CONCLUSIONS Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation . Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implication s for developing future inhaled treatments", "Background : Little is known about adherence to inhaled medication in chronic obstructive pulmonary disease ( COPD ) and the impact on mortality and morbidity . Methods : Data on drug adherence from a r and omised double-blind trial comparing inhaled salmeterol 50 μg + fluticasone propionate 500 μg twice daily with placebo and each drug individually in 6112 patients with moderate to severe COPD over 3 years in the TORCH study were used . All-cause mortality and exacerbations leading to hospital admission were primary and secondary end points . The study of adherence was not specified a priori as an ancillary study . Results : Of the 4880 patients ( 79.8 % ) with good adherence defined as > 80 % use of study medication , 11.3 % died compared with 26.4 % of the 1232 patients ( 20.2 % ) with poor adherence . The annual rates of hospital admission for exacerbations were 0.15 and 0.27 , respectively . The association between adherence and mortality remained unchanged and statistically significant after adjusting for other factors related to prognosis ( hazard ratio 0.40 ( 95 % CI 0.35 to 0.46 ) , p between adherence and hospital admission remained unchanged and significant in a multivariate analysis ( rate ratio 0.58 ( 95 % CI 0.44 to 0.73 , p increased adherence and improved mortality and reduction in hospital admission was independent of study treatment . The effect of treatment was more pronounced in patients with good adherence than in those with poor adherence . Conclusion : Adherence to inhaled medication is significantly associated with reduced risk of death and admission to hospital due to exacerbations in COPD . Further research is needed to underst and these strong associations", "OBJECTIVES The goal of comparative effectiveness analysis is to examine the relationship between two variables , treatment , or exposure and effectiveness or outcome . Unlike data obtained through r and omized controlled trials , research ers face greater challenges with causal inference with observational studies . Recognizing these challenges , a task force was formed to develop a guidance document on method ological approaches to addresses these biases . METHODS The task force was commissioned and a Chair was selected by the International Society for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007 . This report , the second of three reported in this issue of the Journal , discusses the inherent biases when using secondary data sources for comparative effectiveness analysis and provides method ological recommendations to help mitigate these biases . RESULTS The task force report provides recommendations and tools for research ers to mitigate threats to validity from bias and confounding in measurement of exposure and outcome . Recommendations on design of study included : the need for data analysis plan with causal diagrams ; detailed attention to classification bias in definition of exposure and clinical outcome ; careful and appropriate use of restriction ; extreme care to identify and control for confounding factors , including time-dependent confounding . CONCLUSIONS Design of nonr and omized studies of comparative effectiveness face several daunting issues , including measurement of exposure and outcome challenged by misclassification and confounding . Use of causal diagrams and restriction are two techniques that can improve the theoretical basis for analyzing treatment effects in study population s of more homogeneity , with reduced loss of generalizability", "Evidence -based health care decisions are best informed by comparisons of all relevant interventions used to treat conditions in specific patient population s. Observational studies are being performed to help fill evidence gaps . Widespread adoption of evidence from observational studies , however , has been limited because of various factors , including the lack of consensus regarding accepted principles for their evaluation and interpretation . Two task forces were formed to develop question naires to assist decision makers in evaluating observational studies , with one Task Force addressing retrospective research and the other Task Force addressing prospect i ve research . The intent was to promote a structured approach to reduce the potential for subjective interpretation of evidence and drive consistency in decision making . Separately developed question naires were combined into a single question naire consisting of 33 items . These were divided into two domains : relevance and credibility . Relevance addresses the extent to which findings , if accurate , apply to the setting of interest to the decision maker . Credibility addresses the extent to which the study findings accurately answer the study question . The question naire provides a guide for assessing the degree of confidence that should be placed from observational studies and promotes awareness of the subtleties involved in evaluating those", "Background : Although inhaled corticosteroids have an established role in the treatment of asthma , studies have tended to concentrate on non-smokers and little is known about the possible effect of cigarette smoking on the efficacy of treatment with inhaled steroids in asthma . A study was undertaken to investigate the effect of active cigarette smoking on responses to treatment with inhaled corticosteroids in patients with mild asthma . Methods : The effect of treatment with inhaled fluticasone propionate ( 1000 μg daily ) or placebo for 3 weeks was studied in a double blind , prospect i ve , r and omised , placebo controlled study of 38 steroid naïve adult asthmatic patients ( 21 non-smokers ) . Efficacy was assessed using morning and evening peak expiratory flow ( PEF ) readings , spirometric parameters , bronchial hyperreactivity , and sputum eosinophil counts . Comparison was made between responses to treatment in non-smoking and smoking asthmatic patients . Results : There was a significantly greater increase in mean morning PEF in non-smokers than in smokers following inhaled fluticasone ( 27 l/min v –5 l/min ) . Non-smokers had a statistically significant increase in mean morning PEF ( 27 l/min ) , mean forced expiratory volume in 1 second ( 0.17 l ) , and geometric mean PC20 ( 2.6 doubling doses ) , and a significant decrease in the proportion of sputum eosinophils ( –1.75 % ) after fluticasone compared with placebo . No significant changes were observed in the smoking asthmatic patients for any of these parameters . Conclusions : Active cigarette smoking impairs the efficacy of short term inhaled corticosteroid treatment in mild asthma . This finding has important implication s for the management of patients with mild asthma who smoke", "CMAJ • MAY 12 , 2009 • 180(10 ) © 2009 Canadian Medical Association or its licensors E47 R and omized trials have traditionally been broadly categorized as either an effectiveness trial or an efficacy trial , although we prefer the terms “ pragmatic ” and “ explanatory . ” Schwartz and Lellouch described these 2 approaches toward clinical trials in 1967 . These authors coined the term “ pragmatic ” to describe trials that help users choose between options for care , and “ explanatory ” to describe trials that test causal research hypotheses ( i.e. , that a given intervention causes a particular benefit ) . We take the view that , in general , pragmatic trials are primarily design ed to determine the effects of an intervention under the usual conditions in which it will be applied , whereas explanatory trials are primarily design ed to determine the effects of an intervention under ideal circumstances . Thus , these terms refer to a trial ’s purpose and , in turn , structure . The degree to which this purpose is met depends on decisions about how the trial is design ed and , ultimately , conducted . Very few trials are purely pragmatic or explanatory . For example , in an otherwise explanatory trial , there may be some aspect of the intervention that is beyond the investigator ’s control . Similarly , the act of conducting an otherwise pragmatic trial may impose some control result ing in the setting being not quite usual . For example , the very act of collecting data required for a trial that would not otherwise be collected in usual practice could be a sufficient trigger to modify participant behaviour in unanticipated ways . Further , several aspects of a trial are relevant , relating to choices of trial participants , health care practitioners , interventions , adherence to protocol and analysis . Thus , we are left with a multidimensional continuum rather than a dichotomy , and a particular trial may display varying levels of pragmatism across these dimensions . In this article , we describe an effort to develop a tool to assess and display the position of any given trial within the pragmatic – explanatory continuum . The primary aim of this tool is to help trialists assess the degree to which design decisions align with the trial ’s stated purpose ( decision-making v. explanation ) . Our tool differs , therefore , from that of Gartlehner and associates in that it is intended to inform trial design rather than provide a method of classifying trials for the purpose of systematic review s. It can , however , also be used by research funders , ethics committees , trial registers and journal editors to make the same assessment , provided trialists declare their intended purpose and adequately report their design decisions . Hence , reporting of pragmatic trials is addressed elsewhere", "Real-world research can use observational or clinical trial design s , in both cases putting emphasis on high external validity , to complement the classical efficacy r and omized controlled trials ( RCTs ) with high internal validity . Real-world research is made necessary by the variety of factors that can play an important a role in modulating effectiveness in real life but are often tightly controlled in RCTs , such as comorbidities and concomitant treatments , adherence , inhalation technique , access to care , strength of doctor-caregiver communication , and socio-economic and other organizational factors . Real-world studies belong to two main categories : pragmatic trials and observational studies , which can be prospect i ve or retrospective . Focusing on comparative data base observational studies , the process aim ed at ensuring high- quality research can be divided into three parts : preparation of research , analyses and reporting , and discussion of results . Key points include a priori planning of data collection and analyses , identification of appropriate data base(s ) , proper outcomes definition , study registration with commitment to publish , bias minimization through matching and adjustment processes accounting for potential confounders , and sensitivity analyses testing the robustness of results . When these conditions are met , observational data base studies can reach a sufficient level of evidence to help create guidelines ( i.e. , clinical and regulatory decision-making )", "OBJECTIVE To evaluate treatment compliance and use of inhaled medications of patients with asthma receiving complementary pharmaceutical care . METHODS A controlled prospect i ve parallel study involving a study group and a control group . We selected 60 patients with persistent asthma and using metered-dose inhalers ( MDIs ) , dry powder inhalers ( DPIs ) or both . The patients were evaluated three times over 60 days . Instructions were provided to the patients in the study group at all visits but only at the first visit to those in the control group . The patients using 120 % of the total number of prescribed doses were classified as noncompliant . The inhalation technique was quantified by a scoring system . A satisfactory technique was defined as a score higher than 7 ( maximum , 9 ) for MDIs and higher than 4 ( maximum , 5 ) for DPIs . RESULTS The final study sample comprised 28 study group patients and 27 control group patients , of whom 18 ( 64.3 % ) and 20 ( 74.7 % ) , respectively , were considered treatment compliant . From the first to the third visits , there were increases , in the study and control groups , in the median MDI-use score ( from 3 [ range , 0 - 5 ] to 8 [ range , 8 - 9 ] ; p median DPI-use score ( from 3 [ range , 2 - 4 ] to 5 [ range , 4 - 5 ] and from 3 [ range , 2 - 4 ] to 4 [ range , 3 - 5 ] ) . CONCLUSIONS The counseling provided by the pharmacist to the patient was important to assist in the implementation of the appropriate inhalation technique , especially for MDI use", "BACKGROUND Long-term r and omized trials comparing asthma outcomes between inhaled corticosteroids in real-world population s are lacking . As such , rigorously conducted observational studies to complement the findings of r and omized trials are needed . OBJECTIVE We sought to compare asthma-related outcomes over 1 year as recorded in a large primary care data base for patients aged 5 to 60 years receiving a first prescription ( initiation population ) or dose increase ( step-up population ) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone . METHODS We used a retrospective matched cohort study in which patients were matched on baseline demographic and disease severity measures . Co primary outcomes were asthma control ( a composite measure comprising no unplanned visit or hospitalization for asthma , oral corticosteroids , or antibiotics for lower respiratory tract infection ) and exacerbation rate . RESULTS More than 80 % of patients in each population achieved asthma control ; 10 % and 16 % of patients in the initiation and step-up population s , respectively , received add-on or combination therapy during the year . Fluticasone was prescribed at significantly higher doses than HFA-beclomethasone for both population s ( P initiation population ( n = 1319 in each cohort ) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.30 ( 95 % CI , 1.02 - 1.65 ) relative to fluticasone . In the step-up population ( cohorts : n = 250 ) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22 ( 95 % CI , 0.66 - 2.26 ) . Exacerbation rates were similar between cohorts . CONCLUSIONS In a real-world setting patients receiving HFA-beclomethasone had a similar or better chance of achieving asthma control at lower prescribed doses than with fluticasone", "OBJECTIVES To estimate the prevalence of partly controlled and uncontrolled asthmatic patients , to evaluate quality of life and healthcare re source consumption . METHODS Cross-sectional phase followed by a 12-month prospect i ve phase . Asthma Control Test and the EQ-5D were used . RESULTS 2853 adult patients recruited in 56 Hospital Respiratory Units in Italy were evaluated : 64.4 % had controlled asthma , 15.8 % partly controlled asthma and 19.8 % were uncontrolled . The mean ( SD ) EQ-5D score was 0.86 ( 0.17 ) in controlled , 0.75 ( 0.20 ) in partly controlled and 0.69 ( 0.23 ) in uncontrolled patients ( p number of patients requiring hospitalization or emergency room visits was lower in controlled ( 1.8 % and 1.6 % , respectively ) than in partly controlled ( 5.1 % and 11.5 % ) and uncontrolled ( 6.4 % and 18.6 % ) . A combination of an inhaled corticosteroid and a long-acting beta-2 agonist was the reported therapy by 56.0 % of patients , with the rate of controlled asthma and improved quality of life being higher in patients on extrafine beclomethasone/formoterol compared to budesonide/formoterol ( p fluticasone/salmeterol ( p Italian patients . Differences may be detected in a real-life setting in favor of extrafine beclomethasone/formoterol combination ", "OBJECTIVE To comprehensively evaluate clinical , economic , and patient-reported outcomes associated with various therapeutic classes of asthma controller medications . PATIENTS AND METHODS This observational study , which used administrative cl aims data from US commercial health plans , included patients with asthma aged 18 through 64 years who filled a prescription for at least 1 asthma controller medication from September 1 , 2003 , through August 31 , 2005 . Outcome metrics included the use of short-acting beta-agonists ( SABAs ) , the use of oral corticosteroids , inpatient (INP)/emergency department ( ED ) visits , and asthma-related health care costs . A subset of 5000 patients was r and omly selected for a survey using the Mini-Asthma Quality of Life Question naire , the Work Productivity and Activity Impairment question naire , and the Asthma Therapy Assessment Question naire . RESULTS Of 56,168 eligible patients , 823 returned completed question naires . Compared with inhaled corticosteroids ( ICSs ) , leukotriene modifiers ( LMs ) were associated with lower odds of INP/ED visits ( odds ratio [ OR ] , 0.80 ; P higher annual cost ( $ 193 ; P INP/ED visits ( OR , 1.74 ; P=.04 ) , lower odds of using 6 or more SABA canisters ( OR , 0.46 ; P higher annual cost ( $ 235 ; P , ICS plus a long-acting beta-agonist consistently showed at least equivalent or better outcomes in the use of SABAs and oral corticosteroids , the risk of INP/ED visits , cost , asthma control level , quality of life , and impairment in productivity and activity . CONCLUSION Inhaled corticosteroids were associated with a lower risk of INP/ED visits , and a lower cost if adherence was achieved . When adherence can not be achieved , LMs may be a reasonable alternative . Combination therapy with ICS plus a long-acting beta-agonist was associated with better or equivalent clinical , economic , and patient-reported outcomes", "OBJECTIVE To evaluate the effect of a short-term individualized education program on adherence to asthma treatment , inhalation techniques , and asthma control . METHODS A prospect i ve study involving patients aged 14 years or older , with a confirmed diagnosis of asthma and recruited from the asthma outpatient clinic of a university hospital in the city of Porto Alegre , Brazil . The study was conducted in two phases ( before and after the educational intervention ) . At a routine medical visit , the participants completed a general question naire in order to assess the level of asthma control and inhalation techniques . The participants also underwent pulmonary function testing . Subsequently , they participated in an asthma education program , which consisted of one individualized session . The participants were reevaluated after three months . RESULTS Of the 174 patients recruited , 115 completed the study . Between the first and second evaluations , there was a significant improvement in the effective use of inhaled corticosteroids ( 90.4 % vs. 93.3 % ; p = 0.003 ) , the effective use of long-acting β2 agonists ( 57.4 % vs. 63.5 % ; p effective use of a combined regimen with these two medications ( 57.4 % vs. 62.6 % ; p the self-reported adherence to corticosteroid therapy ( p = 0.001 ) . There was a significant decrease in the proportion of patients visiting ERs ( 30.4 % vs. 23.5 % ; p = 0.012 ) . However , the level of asthma control and the inhalation technique did not improve significantly ( p = 0.095 and p = 0.512 , respectively ) . CONCLUSIONS This short-term asthma education program result ed in an improvement in the use of medications for asthma control and a decrease in the number of ER visits , although it had no significant effect on the inhalation technique", "RATIONALE Guidelines advocate adding long-acting β-agonist ( LABA ) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy . However , less than 5 % of patients with asthma qualify for the r and omized controlled trials on which guidelines are based . Thus , real-world data are needed to complement the results of r and omized trials with narrow entry criteria . OBJECTIVES To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA . METHODS We performed a historical matched cohort study using large primary care data bases to compare asthma step-up therapy with small- and st and ard size-particle inhaled corticosteroid versus added LABA for patients 12 - 80 years old . As outcomes , we examined a composite of asthma control and rates of severe exacerbations . MEASUREMENTS AND MAIN RESULTS The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA . The adjusted odds ratios ( 95 % confidence interval ) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 ( 0.88 - 1.12 ) for small-particle inhaled corticosteroid ( n = 3,036 per cohort ) and 0.85 ( 0.67 - 1.07 ) for st and ard size-particle inhaled corticosteroid ( n = 809 per cohort ) . The adjusted rate ratios ( 95 % confidence interval ) for severe exacerbations , compared with inhaled corticosteroid/LABA combination inhaler , were 1.04 ( 0.91 - 1.20 ) and 1.18 ( 0.92 - 1.54 ) , respectively . The results were not affected by smoking status . CONCLUSIONS When applied to a broad primary care population , antiinflammatory therapy using increased doses of small- or st and ard size-particle inhaled corticosteroid is as effective as adding LABA , as measured by outcomes important to both patients and providers . Real-world population s and outcomes need to be taken into consideration when formulating treatment recommendations", "Are pharmacological r and omised controlled clinical trials relevant to real-life asthma population s ? : A protocol for an UNLOCK study from the", "BACKGROUND In an attempt to establish how treatment with inhaled extra-fine beclomethasone/formoterol ( I-EF-BDP/F ) formulation differs from other combinations of inhaled corticosteroid ( ICS ) and long acting beta-agonist ( LABA ) , we studied lung function and markers of airway inflammation upon switching to the extra-fine formulation and after 8 weeks of treatment with it . METHODS We carried out a real-life clinical observation of undercontrolled asthmatic patients switched over from dry powder inhalers of fluticasone/salmeterol and budesonide/formoterol to I-EF-BDP/F ( Foster ( ® ) , Chiesi Farmaceutici S.p . A. , Italy ) . The effects of 8-weeks of treatment were documented by means of visual analog scale ( VAS ) , quality of life by Asthma Quality of Life Question naire ( AQLQ ) , spirometry and markers of airway or systemic inflammation : exhaled breath temperature ( EBT ) , blood eosinophils ( Eos ) , and high sensitivity C-reactive protein ( CRP ) . Before/after treatment differences between forced vital capacity percent of predicted ( % FVC ) , a simple indicator of small airways involvement , were calculated and subjects were ranked accordingly to reflect the magnitude of the therapeutic response . Subjects above the 75th percentile ( n = 15 ) , \" top responders \" , were then compared with those below the 25th percentile ( n = 15 ) \" poor responders \" . RESULTS On average , the 59 patients completing the study ( mean age ± SD 51 ± 12 years , 38 women ) had significant improvement in VAS and QLQ scores at the end of the treatment period ( 49.1 ± 2.4 vs. 73.1 ± 2.05 and 146.1 ± 2.7 vs. 176.7.1 ± 3.4 respectively , P ) , but not in the inflammatory indicators ( EBT , CRP and Eos ) . However , when comparing the \" top responders \" with the \" poor responders \" , significant improvement in these inflammatory indicators was observed : EBT significantly decreased from 34.04/mean/± 0.30/s.e.m./[ ° C ] to 33.57 ± 0.33 , P = 0.003 , Eos in blood fell from 381.7 ± 91.2 [ cells/μL ] to 244.2 ± 43.2 , P = 0.02 . Before/after treatment differences in hsCRP decreased significantly in the top responders compared with the poor responders ( Mann-Whitney test , P = 0.04 ) . CONCLUSION Asthmatic subjects who had the most improvement in FVC after transition to I-EF-BDP/F from other combined ICS/LABA preparations also demonstrated a significant decrease in some indicators of airway/systemic inflammation . These results support the notion that I-EF-BDP/F exerts an effect also at the level of the small airways through a reduction of the level of air trapping . Patients in whom inflammation of the small airways plays an important clinical role are the ones to derive most benefit from this small airways tailored treatment . However , improved compliance due to the \" promise of a new drug \" effect should also be considered as contributing to the treatment results", "Poor inhaler technique is frequent in asthma , but its long-term consequences have been seldom assessed . Pharmacists are ideally positioned to teach inhaler technique . This prospect i ve observational study evaluated the feasibility of inhaler training by pharmacists in patients receiving inhaled corticosteroids by pressurised metered-dose inhaler ( pMDI ) or breath-actuated MDI . In parallel , the relationships between inhaler technique , adherence , and asthma control , and their modulation one month after training were assessed . Of 727 patients receiving training at pharmacies ( n=123 ) , 61 % were prescribed a pMDI ; 35 % , an Autohaler ( ® ) ; and 5 % , an Easi-Breathe ( ® ) inhaler . Poor asthma control ( Asthma Control Question naire score ≥ 1.5 ) at baseline was significantly ( p poor inhaler technique and poor self-reported adherence ( Morisky score ≥ 3 ) . The percentage of patients with optimal inhaler technique rose from 24 % before to 79 % after training ( p Median training session length was 6 min . At 1 month , mean ( SD ) ACQ score had improved from a baseline score of 1.8 ( 1.2 ) to 1.4 ( 1.1 ) , ( p observed for Morisky score . Inhaler technique is associated with adherence and influences asthma control . Inhaler training by pharmacists is feasible and seams to improve inhaler technique , asthma control and adherence ", "OBJECTIVE To determine the rate of adherence to treatment with inhaled corticosteroids in patients with severe asthma , to identify predictive factors for adherence and to evaluate the relationship between adherence to treatment and parameters of clinical and functional response . METHODS Prospect i ve cohort study of patients enrolled in the Program for the Control of Asthma and Allergic Rhinitis in the state of Bahia , Brazil . The study comprised 160 patients with severe asthma , monitored for 180 days in order to evaluate adherence ( dependent variable ) to the prescribed inhaled corticosteroid . Independent variables were assessed at baseline and for a six-month follow-up period by means of interviews and the completion of a st and ardized question naire . Patients recorded the missed doses in a diary . RESULTS Of the 160 patients . 158 completed the study . Adherence rate was 83.8 % . Of the 158 patients , 112 ( 70.9 % ) were considered adherent ( cut-off point : 80 % of prescribed doses administered ) . There was a significant association between asthma control and adherence to treatment . Predictors of poor adherence were adverse effects , living far from the referral center , limited re sources to pay for transportation and dose schedule . Other factors , such as depressive symptoms , religion and economic status , were not associated with poor adherence . CONCLUSIONS Adherence to asthma treatment was high and was associated with the clinical response to treatment , in a sample of patients with severe asthma enrolled in a public program that provides free medication and the assistance of a multiprofessional specialized team in a referral center", "BACKGROUND This study tested the hypothesis that there would be improved asthma control with increasing doses of beclomethasone dipropionate ( BDP ) formulated in hydrofluoroalkane-134a ( HFA-BDP ) and the st and ard chlorofluorocarbon propellants ( CFC-BDP ) . Because HFA-BDP has improved lung deposition compared with CFC-BDP , this study also tested the hypothesis that HFA-BDP would provide more effective control of asthma than CFC-BDP . METHODS In this multicenter , r and omized , parallel-group blinded study , asthmatic subjects who had deterioration in asthma control after discontinuation of inhaled corticosteroids were r and omized to receive one of 6 possible treatments : 100 microg/d , 400 microg/d , or 800 microg/d of HFA-BDP or 100 microg/d , 400 microg/d , or 800 microg/d of CFC-BDP for 6 weeks . Changes in spirometry , daytime asthma symptom and nighttime asthma-related sleep disturbance scores , morning and evening peak expiratory flows , and daily use of inhaled beta-agonist for symptom control on diary cards were assessed over 6 weeks of treatment . RESULTS Three hundred twenty-three patients were r and omized to the 6 treatment groups , which had similar demographics and baseline lung function . There were significantly larger changes from baseline at week 6 in FEV(1 ) percent predicted with increasing doses of both HFA-BDP and CFC-BDP . The FEV(1 ) percent predicted dose-response curve for HFA-BDP was shifted to the left compared with the dose-response curve for CFC-BDP . By using the Finney bioassay method , it was calculated that 2.6 times as much CFC-BDP would be required to achieve the same improvement in FEV(1 ) percent predicted as HFA-BDP ( 95 % confidence interval , 1.1 - 11.6 ) . All treatment groups except the 100 microg/d CFC-BDP group tolerated study drug well . Ten ( 17 % ) of 59 patients in this group reported an acute asthma episode , increased asthma symptoms ( 6 of the 8 reports of increased asthma symptoms were classified as severe ) , or both , and 8 patients withdrew from the study ( 3 for adverse events related to asthma ) . CONCLUSIONS Increasing doses of inhaled corticosteroids lead to improved lung function and asthma control . Moreover , the reformulation of BDP in HFA enables effective asthma control at much lower doses than CFC-BDP", "Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials", "Abstract Background Evidence from observational comparative effectiveness research ( CER ) is ranked below that from r and omized controlled trials in traditional evidence hierarchies . However , asthma observational CER studies represent an important complementary evidence source answering different research questions and are particularly valuable in guiding clinical decision making in real-life patient and practice setting s. Tools are required to assist in quality appraisal of observational CER to enable identification of and confidence in high- quality CER evidence to inform guideline development . Methods The REal Life EVidence AssessmeNt Tool ( RELEVANT ) was developed through a step-wise approach . We conducted an iterative refinement of the tool based on Task Force member expertise and feedback from pilot testing the tool until reaching adequate inter-rater agreement percentages . Two distinct pilots were conducted — the first involving six members of the Respiratory Effectiveness Group ( REG ) and European Academy of Allergy and Clinical Immunology ( EAACI ) joint Task Force for quality appraisal of observational asthma CER ; the second involving 22 members of REG and EAACI membership . The final tool consists of 21 quality sub-items distributed across seven methodology domains : Background , Design , Measures , Analysis , Results , Discussion /Interpretation , and Conflict of Interest . Eleven of these sub-items are considered critical and named “ primary sub-items ” . Results Following the second pilot , RELEVANT showed inter-rater agreement ≥ 70 % for 94 % of all primary and 93 % for all secondary sub-items tested across three rater groups . For observational CER to be classified as sufficiently high quality for future guideline consideration , all RELEVANT primary sub-items must be fulfilled . The ten secondary sub-items further qualify the relative strengths and weaknesses of the published CER evidence . RELEVANT could also be applicable to general quality appraisal of observational CER across other medical specialties . Conclusions RELEVANT is the first quality checklist to assist in the appraisal of published observational CER developed through iterative feedback derived from pilot implementation and inter-rater agreement evaluation . Developed for a REG-EAACI Task Force quality appraisal of recent asthma CER , RELEVANT also has wider utility to support appraisal of CER literature in general ( including pre-publication ) . It may also assist in manuscript development and in educating relevant stakeholders about key quality markers in observational CER", "This Cochrane review contains 29 r and omised controlled trials ( RCT ) involving 2210 participants ( range 21–201 ) ( Normansell et al. , 2017 ) . Included studies targeted adults and adolescents ( aged 12 years and over ) and children ( aged under 12 years ) with asthma . Follow-up ranged from 2 to 26 weeks . Participants with other respiratory comorbidities , including chronic obstructive pulmonary disease and bronchiectasis , were excluded . Studies examined interventions conducted in hospital , primary care , community or outpatient care setting s. These included interventions aim ed at improving inhaler technique compared with usual care with no additional intervention , or with alternative interventions such as asthma education only or a different type/intensity of inhaler technique intervention . Twelve studies evaluated enhanced face-to-face training , nine used multimedia-delivered training and the rest used technique feedback devices . Studies were conducted in Europe ( n= 11 , of which 6 were in UK and 1 each in Belgium , Denmark , France , Irel and and Italy ) , USA ( n= 7 ) , Australia ( n= 4 ) , Asia ( n= 3 ) , Africa ( n= 1 ) and 3 were of unknown origin . Interventions were delivered by trained health care professionals including nurses , respiratory or physiotherapists , pharmacists and physicians" ]	41182dea-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To summarize the evidence on effectiveness of translational diabetes prevention programs , based on promoting lifestyle change to prevent type 2 diabetes in real-world setting s and to examine whether adherence to international guideline recommendations is associated with effectiveness . RESEARCH DESIGN AND METHODS Bibliographic data bases were search ed up to July 2012 . Included studies had a follow-up of ≥12 months and outcomes comparing change in body composition , glycemic control , or progression to diabetes . Lifestyle interventions aim ed to translate evidence from previous efficacy trials of diabetes prevention into real-world intervention programs . Data were combined using r and om-effects meta- analysis and meta-regression considering the relationship between intervention effectiveness and adherence to guidelines . RESULTS Twenty-five studies met the inclusion criteria . The primary meta- analysis included 22 studies ( 24 study groups ) with outcome data for weight loss at 12 months . The pooled result of the direct pairwise meta- analysis shows that lifestyle interventions result ed in a mean weight loss of 2.32 kg ( 95 % CI −2.92 to −1.72 ; I2 = 93.3 % ) . Adherence to guidelines was significantly associated with a greater weight loss ( an increase of 0.4 kg per point increase on a 12-point guideline -adherence scale ) . CONCLUSIONS Evidence suggests that pragmatic diabetes prevention programs are effective . Effectiveness varies substantially between programs but can be improved by maximizing guideline adherence . However , more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects	[ "Abstract Background Diabetes prevalence is increasing . The Finnish Diabetes Prevention Study ( DPS ) showed a 58 % reduction in Type 2 Diabetes ( T2D ) incidence in adults with impaired glucose tolerance ( IGT ) . The European Diabetes Prevention Study ( EDIPS ) extends the DPS to different European population s , using the same study design . In the Newcastle arm of this study ( EDIPS-Newcastle ) , we tested the hypothesis that T2D can be prevented by lifestyle intervention and explored secondary outcomes in relation to diabetes incidence . Methods We recruited 102 participants ( 42 men and 60 women , mean age 57 years , mean BMI 34 kgm-2 ) with IGT to EDIPS-Newcastle and r and omised to Intervention and usual care Control groups . The intervention included individual motivational interviewing aim ed at : weight reduction , increase in physical activity , fibre and carbohydrate intake and reduction of fat intake ( secondary outcomes ) . The primary outcome was diagnosis of T2D . Results Mean duration of follow-up was 3.1 years . T2D was diagnosed in 16 participants ( I = 5 , C = 11 ) . Absolute incidence of T2D was 32.7 per 1000 person-years in the Intervention-group and 67.1 per 1000 person-years in the Control-group . The overall incidence of diabetes was reduced by 55 % in the Intervention-group , compared with the Control-group : RR 0.45 ( 95%CI 0.2 to 1.2).Explanatory survival analysis of secondary outcomes showed that those who sustained beneficial changes for two or more years reduced their risk of developing T2D . Conclusion Our results are consistent with other diabetes prevention trials . This study was design ed as part of a larger study and although the sample size limits statistical significance , the results contribute to the evidence that T2D can be prevented by lifestyle changes in adults with IGT . In explanatory analysis small sustained beneficial changes in weight , physical activity or dietary factors were associated with reduction in T2D incidence . Trial Registration International St and ard R and omised Controlled Trial Number registry ( IS RCT N)Registry number : IS RCT N 15670600 http://www.controlled-trials.com/is rct n/ search .html?srch=15670600%26sort=3%26dir =", "Background R and omised controlled trials demonstrate a 60 % reduction in type 2 diabetes incidence through lifestyle modification programmes . The aim of this study is to determine whether such programmes are feasible in primary health care . Methods An intervention study including 237 individuals 40–75 years of age with moderate or high risk of developing type 2 diabetes . A structured group programme with six 90 minute sessions delivered during an eight month period by trained nurses in Australian primary health care in 2004–2006 . Main outcome measures taken at baseline , three , and 12 months included weight , height , waist circumference , fasting plasma glucose and lipids , plasma glucose two hours after oral glucose challenge , blood pressure , measures of psychological distress and general health outcomes . To test differences between baseline and follow-up , paired t-tests and Wilcoxon rank sum tests were performed . Results At twelve months participants ' mean weight reduced by 2.52 kg ( 95 % confidence interval 1.85 to 3.19 ) and waist circumference by 4.17 cm ( 3.48 to 4.87 ) . Mean fasting glucose reduced by 0.14 mmol/l ( 0.07 to 0.20 ) , plasma glucose two hours after oral glucose challenge by 0.58 mmol/l ( 0.36 to 0.79 ) , total cholesterol by 0.29 mmol/l ( 0.18 to 0.40 ) , low density lipoprotein cholesterol by 0.25 mmol/l ( 0.16 to 0.34 ) , triglycerides by 0.15 mmol/l ( 0.05 to 0.24 ) and diastolic blood pressure by 2.14 mmHg ( 0.94 to 3.33 ) . Significant improvements were also found in most psychological measures . Conclusion This study provides evidence that a type 2 diabetes prevention programme using lifestyle intervention is feasible in primary health care setting s , with reductions in risk factors approaching those observed in clinical trials . Trial NumberCurrent Controlled Trials IS RCT", "OBJECTIVE To study the overall effect of the Active Prevention in High-Risk Individuals of Diabetes Type 2 in and Around Eindhoven ( APHRODITE ) lifestyle intervention on type 2 diabetes risk reduction in Dutch primary care after 0.5 and 1.5 years and to evaluate the variability between general practice s. RESEARCH DESIGN AND METHODS Individuals at high risk for type 2 diabetes ( Finnish Diabetes Risk Score ≥13 ) were r and omly assigned into an intervention group ( n = 479 ) or a usual-care group ( n = 446 ) . Comparisons were made between study groups and between general practice s regarding changes in clinical and lifestyle measures over 1.5 years . Participant , general practitioner , and nurse practitioner characteristics were compared between individuals who lost weight or maintained a stable weight and individuals who gained weight . RESULTS Both groups showed modest changes in glucose values , weight measures , physical activity , energy intake , and fiber intake . Differences between groups were significant only for total physical activity , saturated fat intake , and fiber intake . Differences between general practice s were significant for BMI and 2-h glucose but not for energy intake and physical activity . In the intervention group , the nurse practitioners ’ mean years of work experience was significantly longer in individuals who were successful at losing weight or maintaining a stable weight compared with unsuccessful individuals . Furthermore , successful individuals more often had a partner . CONCLUSIONS Risk factors for type 2 diabetes could be significantly reduced by lifestyle counseling in Dutch primary care . The small differences in changes over time between the two study groups suggest that additional intervention effects are modest . In particular , the level of experience of the nurse practitioner and the availability of partner support seem to facilitate intervention success", "OBJECTIVE Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance", "BACKGROUND The Diabetes Prevention Program ( DPP ) found that an intensive lifestyle intervention can reduce the development of diabetes by more than half in adults with prediabetes , but there is little information about the feasibility of offering such an intervention in community setting s. This study evaluated the delivery of a group-based DPP lifestyle intervention in partnership with the YMCA . METHODS This pilot cluster-r and omized trial was design ed to compare group-based DPP lifestyle intervention delivery by the YMCA to brief counseling alone ( control ) in adults who attended a diabetes risk-screening event at one of two semi-urban YMCA facilities and who had a BMI > or=24 kg/m2 , > or=2 diabetes risk factors , and a r and om capillary blood glucose of 110 - 199 mg/dL. Multivariate regression was used to compare between-group differences in changes in body weight , blood pressures , HbA1c , total cholesterol , and HDL-cholesterol after 6 and 12 months . RESULTS Among 92 participants , controls were more often women ( 61 % vs 50 % ) and of nonwhite race ( 29 % vs 7 % ) . After 6 months , body weight decreased by 6.0 % ( 95 % CI=4.7 , 7.3 ) in intervention participants and 2.0 % ( 95 % CI=0.6 , 3.3 ) in controls ( p total cholesterol ( -22 mg/dL vs + 6 mg/dL controls ; p YMCA sites , it was not possible to adjust for potential clustering by site . CONCLUSIONS The YMCA may be a promising channel for wide-scale dissemination of a low-cost approach to lifestyle diabetes prevention", "Purpose The objective was to take prevention from the clinic to the community by including a high-risk group and working with the community to tailor , enhance , deliver , and evaluate a community-based version of the Diabetes Prevention Program ’s ( DPP ) clinic-based lifestyle intervention . Methods This was a nonr and omized prospect i ve study using a single-group design . Study eligibility included a screening glucose value in the normal to prediabetes range with no current diagnosis of diabetes , overweight , not pregnant nor planning to become pregnant during study period , aged 18 to 65 , Latino , living in the study target communities , and no reported medical restrictions related to the program goals . A total of 69 individuals participated . The Healthy Living Program ( HLP ) was based on the DPP ’s 1-year intensive lifestyle program , was tailored and enhanced for a Latino community , and was delivered by community health workers . Anthropometric and paper and pencil measures were administered to examine program outcome at 6 months and 12 months . Results In general , results indicate statistically significant improvements in anthropometrics and many behavioral outcomes , particularly at 6 months . Participants demonstrated forward movement through the stages of change during the program . Conclusions Results support the effectiveness of the intervention and show that delivery of the translated version of the DPP ’s lifestyle intervention in the community by community residents holds promise as one strategy to reach people at increased risk of developing diabetes . Use of this translation model , including collaboration with community health workers , offers diabetes educators an opportunity to extend their reach into underserved communities", "OBJECTIVE To develop a simple question naire to prospect ively identify individuals at increased risk for undiagnosed diabetes . RESEARCH DESIGN AND METHODS People with newly diagnosed diabetes ( n = 164 ) identified in the Second National Health and Nutrition Examination Survey and those with neither newly diagnosed diabetes nor a history of physician-diagnosed diabetes ( n = 3,220 ) were studied . Major historical risk factors for undiagnosed non-insulin-dependent diabetes were defined , and classification trees were developed to identify people at higher risk for previously undiagnosed diabetes . The sensitivity , specificity , and predictive value of the classification trees were described and compared with those of an existing question naire . RESULTS The selected classification tree incorporated age , sex , history of delivery of a macrosomic infant , obesity , sedentary lifestyle , and family history of diabetes . In a representative sample of the U.S. population , the sensitivity of the tree was 79 % , the specificity was 65 % , and the predictive value positive was 10 % . CONCLUSIONS This classification tree performed significantly better than an existing question naire and should serve as a simple , noninvasive , and potentially cost-effective tool for diagnosing diabetes in the", "Background Lifestyle change is probably the most important single action to prevent type 2 diabetes mellitus . The purpose of this study was to assess the effects of a low-intensity individual lifestyle intervention by a physician and compare this to the same physician intervention combined with an interdisciplinary , group-based approach in a real-life setting . Methods The \" Finnish Diabetes Risk score \" ( FINDRISC ) was used by GPs to identify individuals at high risk . A r and omised , controlled design and an 18 month follow-up was used to assess the effect of individual lifestyle counselling by a physician ( individual physician group , ( IG ) ) every six months , with emphasis on diet and exercise , and compare this to the same individual lifestyle counselling combined with a group-based interdisciplinary program ( individual and interdisciplinary group , ( IIG ) ) provided over 16 weeks . Primary outcomes were changes in lifestyle indicated by weight reduction ≥ 5 % , improvement in exercise capacity as assessed by VO2 max and diet improvements according to the Smart Diet Score ( SDS ) . Results 213 participants ( 104 in the IG and 109 in the IIG group , 50 % women ) , with a mean age of 46 and mean body mass index 37 , were included ( inclusion rate > 91 % ) of whom 182 returned at follow-up ( drop-out rate 15 % ) . There were no significant differences in changes in lifestyle behaviours between the two groups . At baseline 57 % ( IG ) and 53 % ( IIG ) of participants had poor aerobic capacity and after intervention 35 % and 33 % , respectively , improved their aerobic capacity at least one metabolic equivalent . Unhealthy diets according to SDS were common in both groups at baseline , 61 % ( IG ) and 60 % ( IIG ) , but uncommon at follow-up , 17 % and 10 % , respectively . At least 5 % weight loss was achieved by 35 % ( IG ) and 28 % ( IIG ) . In the combined IG and IIG group , at least one primary outcome was achieved by 93 % while all primary outcomes were achieved by 6 % . Most successful was the 78 % reduction in the proportion of participants with unhealthy diet ( almost 50 % absolute reduction ) . Conclusion It is possible to achieve important lifestyle changes in persons at risk for type 2 diabetes with modest clinical efforts . Group intervention yields no additional effects . The design of the study , with high inclusion and low dropout rates , should make the results applicable to ordinary clinical setting s . Trial registration Clinical Trials.gov :", "OBJECTIVE Although the Diabetes Prevention Program ( DPP ) and the Finnish Diabetes Prevention Study ( FDPS ) demonstrated that weight loss from lifestyle change reduces type 2 diabetes incidence in patients with prediabetes , the translation into community setting s has been difficult . The objective of this study is to report the first-year results of a community-based translation of the DPP lifestyle weight loss ( LWL ) intervention on fasting glucose , insulin resistance , and adiposity . RESEARCH DESIGN AND METHODS We r and omly assigned 301 overweight and obese volunteers ( BMI 25–40 kg/m2 ) with fasting blood glucose values between 95 and 125 mg/dL to a group-based translation of the DPP LWL intervention administered through a diabetes education program ( DEP ) and delivered by community health workers ( CHWs ) or to an enhanced usual-care condition . CHWs were volunteers with well-controlled type 2 diabetes . A total of 42.5 % of participants were male , mean age was 57.9 years , 26 % were of a race/ethnicity other than white , and 80 % reported having an education beyond high school . The primary outcome is mean fasting glucose over 12 months of follow-up , adjusting for baseline glucose . RESULTS Compared with usual-care participants , LWL intervention participants experienced significantly greater decreases in blood glucose ( −4.3 vs. −0.4 mg/dL ; P 0.001 ) , insulin ( −6.5 vs. −2.7 μU/mL ; P ( −1.9 vs. −0.8 ; P ( −7.1 vs. −1.4 kg ; P ) , BMI ( −2.1 vs. −0.3 kg/m2 ; P ) , and waist circumference ( −5.9 vs. −0.8 cm ; P translation of the DPP intervention conducted in community setting s , administered through a DEP , and delivered by CHWs holds great promise for the prevention of diabetes by significantly decreasing glucose , insulin , and adiposity ", "Introduction Although lifestyle interventions are effective in delaying the onset of diabetes , translating these lessons to routine health care setting s remains a challenge . We investigated the effectiveness of a theory-based , brief , small-group weight loss intervention for diabetes prevention . A secondary purpose was to determine the potential reach of the intervention . Methods A total of 14,379 members of an integrated health care organization newly diagnosed with prediabetes were potentially eligible to participate in this matched cohort longitudinal study . Of this group , 1,030 attended a 90-minute , small-group session that targeted personal action planning for healthful eating , physical activity , and weight management . We accessed electronic medical records to select 1 to 2 controls ( matched on impaired fasting glucose measurement , sex , age , and body mass index ) for each member who attended the small-group session ( n = 760 ) . Weight change , as recorded in the medical record , was the primary outcome . Mixed models analyses were used to adjust for matching variables and covariates and to account for individual r and om effects over time . Results Small-group participants lost significantly more weight than did their matched controls . A significantly higher proportion of small-group participants lost at least 5 % of their body weight compared with controls . Conclusion A brief , small-group weight loss intervention was effective . However , it did not reach broadly into the population that was at risk for diabetes", "OBJECTIVE —The purpose of this study was to assess the effectiveness of a low – re source -intensive lifestyle modification program incorporating resistance training and to compare a gymnasium-based with a home-based resistance training program on diabetes diagnosis status and risk . RESEARCH DESIGN AND METHODS —A quasi-experimental two-group study was undertaken with 122 participants with diabetes risk factors ; 36.9 % had impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) at baseline . The intervention included a 6-week group self-management education program , a gymnasium-based or home-based 12-week resistance training program , and a 34-week maintenance program . Fasting plasma glucose ( FPG ) and 2-h plasma glucose , blood lipids , blood pressure , body composition , physical activity , and diet were assessed at baseline and week 52 . RESULTS —Mean 2-h plasma glucose and FPG fell by 0.34 mmol/l ( 95 % CI −0.60 to −0.08 ) and 0.15 mmol/l ( −0.23 to −0.07 ) , respectively . The proportion of participants with IFG or IGT decreased from 36.9 to 23.0 % ( P = 0.006 ) . Mean weight loss was 4.07 kg ( −4.99 to −3.15 ) . The only significant difference between resistance training groups was a greater reduction in systolic blood pressure for the gymnasium-based group ( P = 0.008 ) . CONCLUSIONS —This intervention significantly improved diabetes diagnostic status and reduced diabetes risk to a degree comparable to that of other low – re source -intensive lifestyle modification programs and more intensive interventions applied to individuals with IGT . The effects of home-based and gymnasium-based resistance training did not differ significantly", "OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system", "Background A r and omized control trial was performed to test whether a lifestyle intervention program , carried out in a primary healthcare setting using existing re sources , can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance ( IGT ) . The results of 3 years ' intervention are summarized . Methods Through health checkups in communities and workplaces , 304 middle-aged IGT subjects with a mean body mass index ( BMI ) of 24.5 kg/m2 were recruited and r and omized to the intervention group or control group . The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational material s provided by the study group . Results After 1 year , the intervention had significantly improved body weight ( -1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control ; p = 0.023 ) and daily non-exercise leisure time energy expenditure ( 25 ± 113 vs. -3 ± 98 kcal ; p = 0.045 ) . Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years . The 3-year cumulative incidence tended to be lower in the intervention group ( 14.8 % vs.8.2 % , log-rank test : p = 0.097 ) . In a sub- analysis for the subjects with a BMI > 22.5 kg/m2 , a significant reduction in the cumulative incidence was found ( p = 0.027 ) . Conclusions The present lifestyle intervention program using existing healthcare re sources is beneficial in preventing diabetes in Japanese with IGT . This has important implication s for primary healthcare-based diabetes prevention . Trial registration", "OBJECTIVE To investigate whether a pragmatic structured education program with and without pedometer use is effective for promoting physical activity and improving glucose tolerance in those with impaired glucose tolerance ( IGT ) . RESEARCH DESIGN AND METHODS Overweight and obese individuals with IGT were recruited from ongoing screening studies at the University Hospitals of Leicester , U.K. Participants were r and omly assigned to one of three groups . Group 1 received a 3-h group-based structured education program design ed to promote walking activity using personalized steps-per-day goals and pedometers . Group 2 received a 3-h group-based structured education program design ed to promote walking activity using generic time-based goals . Group 3 received a brief information leaflet ( control condition ) . Outcomes included an oral glucose tolerance test , st and ard anthropometric measures , ambulatory activity , and psychological variables . Follow-up was conducted at 3 , 6 , and 12 months . RESULTS A total of 87 individuals ( 66 % male , mean age 65 years ) were included in this study . At 12 months , significant decreases in 2-h postchallenge glucose and fasting glucose of −1.31 mmol/l ( 95 % CI −2.20 to −0.43 ) and −0.32 mmol/l ( −0.59 to −0.03 ) , respectively , were seen in the pedometer group compared with the control group . No significant improvements in glucose control were seen in those given the st and ard education program . CONCLUSIONS This study suggests that a pragmatic structured education program that incorporates pedometer use is effective for improving glucose tolerance in those with IGT . This result is likely to have important implication s for future primary care – based diabetes prevention initiatives", "OBJECTIVES Our community-academic partnership employed community-based participatory research to develop and pilot a simple , peer-led intervention to promote weight loss , which can prevent diabetes and eliminate racial/ethnic disparities in incident diabetes among overweight adults with prediabetes . METHODS We recruited overweight adults at community sites , performed oral glucose tolerance testing to identify persons with blood glucose levels in the prediabetes range , and r and omized eligible people to a peer-led lifestyle intervention group or delayed intervention in 1 year . Outcomes , including weight , blood pressure , and health behaviors , were measured at baseline and 3 , 6 , and 12 months . RESULTS More than half of those tested ( 56 % , or 99 of 178 ) had prediabetes and enrolled in the study . Participants were predominantly Spanish-speaking , low-income , undereducated women . The intervention group lost significantly more weight than the control group and maintained weight loss at 12 months ( 7.2 versus 2.4 pounds ; P to diabetes . CONCLUSIONS In underserved minority communities , prediabetes prevalence may be higher than previously reported . Low-cost , community-based interventions can succeed in encouraging weight loss to prevent diabetes", "BACKGROUND Type 2 diabetes mellitus is increasingly common , primarily because of increases in the prevalence of a sedentary lifestyle and obesity . Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known . METHODS We r and omly assigned 522 middle-aged , overweight subjects ( 172 men and 350 women ; mean age , 55 years ; mean body-mass index [ weight in kilograms divided by the square of the height in meters ] , 31 ) with impaired glucose tolerance to either the intervention group or the control group . Each subject in the intervention group received individualized counseling aim ed at reducing weight , total intake of fat , and intake of saturated fat and increasing intake of fiber and physical activity . An oral glucose-tolerance test was performed annually ; the diagnosis of diabetes was confirmed by a second test . The mean duration of follow-up was 3.2 years . RESULTS The mean ( + /-SD ) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group ; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group ( P cumulative incidence of diabetes after four years was 11 percent ( 95 percent confidence interval , 6 to 15 percent ) in the intervention group and 23 percent ( 95 percent confidence interval , 17 to 29 percent ) in the control group . During the trial , the risk of diabetes was reduced by 58 percent ( P the incidence of diabetes was directly associated with changes in lifestyle . CONCLUSIONS Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects", "Aims /hypothesisLifestyle modification helps in the primary prevention of diabetes in multiethnic American , Finnish and Chinese population s. In a prospect i ve community-based study , we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger , leaner and more insulin resistant than the above population s. Methods We r and omised 531 ( 421 men 110 women ) subjects with IGT ( mean age 45.9±5.7 years , BMI 25.8±3.5 kg/m2 ) into four groups . Group 1 was the control , Group 2 was given advice on lifestyle modification ( LSM ) , Group 3 was treated with metformin ( MET ) and Group 4 was given LSM plus MET . The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria . Results The median follow-up period was 30 months , and the 3-year cumulative incidences of diabetes were 55.0 % , 39.3 % , 40.5 % and 39.5 % in Groups 1–4 , respectively . The relative risk reduction was 28.5 % with LSM ( 95 % CI 20.5–37.3 , p=0.018 ) , 26.4 % with MET ( 95 % CI 19.1–35.1 , p=0.029 ) and 28.2 % with LSM + MET ( 95 % CI 20.3–37.0 , p=0.022 ) , as compared with the control group . The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM , 6.9 for MET and 6.5 for LSM + MET . Conclusions /interpretationProgression of IGT to diabetes is high in native Asian Indians . Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT ; there was no added benefit from combining them", "BACKGROUND Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes , at least as long as the intervention continues . In the extended follow-up of the Finnish Diabetes Prevention Study , we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling . METHODS Overweight , middle-aged men ( n=172 ) and women ( n=350 ) with impaired glucose tolerance were r and omly assigned to intensive lifestyle intervention or control group . After a median of 4 years of active intervention period , participants who were still free of diabetes were further followed up for a median of 3 years , with median total follow-up of 7 years . Diabetes incidence , bodyweight , physical activity , and dietary intakes of fat , saturated fat , and fibre were measured . FINDINGS During the total follow-up , the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group , respectively ( log-rank test p=0.0001 ) , indicating 43 % reduction in relative risk . The risk reduction was related to the success in achieving the intervention goals of weight loss , reduced intake of total and saturated fat and increased intake of dietary fibre , and increased physical activity . Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention , and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 ( p=0.0401 ) , indicating 36 % reduction in relative risk . INTERPRETATION Lifestyle intervention in people at high risk for type 2 diabetes result ed in sustained lifestyle changes and a reduction in diabetes incidence , which remained after the individual lifestyle counselling was stopped", "AIMS To determine the effectiveness of a 2.5-year lifestyle intervention for Type 2 diabetes prevention in Dutch general practice compared with usual care . METHODS A r and omized controlled trial of 925 individuals at high risk for Type 2 diabetes ( FINDRISC-score ≥ 13 ) in 14 general practice s in the Netherl and s. Intervention consisted of lifestyle counselling from the nurse practitioner and the general practitioner . Usual care consisted of oral and written information at the start of the study . Study groups were compared over 2.5 years regarding changes in clinical and lifestyle measures . RESULTS Both groups showed modest changes in body weight , glucose concentrations , physical activity and dietary intake [ weight : intervention group , -0.8 ( 5.1 ) kg , usual care group , -0.4 ( 4.7 ) kg , ( P=0.69 ) ; fasting plasma glucose : intervention group , -0.17 ( 0.4 ) mmol/l , usual care group , -0.10 ( 0.5 ) mmol/l , ( P=0.10 ) ] . Differences between groups were significant only for total physical activity and fibre intake . In the intervention group , self-efficacy was significantly higher in individuals successful at losing weight compared with unsuccessful individuals . No significant differences in participant weight loss were found between general practitioners and nurse practitioners with different levels of motivation or self-efficacy . CONCLUSIONS Diabetes risk factors could significantly be reduced by lifestyle counselling in Dutch primary care . However , intervention effects above the effects attributable to usual care were modest . Higher participant self-efficacy seemed to facilitate weight loss . Lack of motivation or self-efficacy of professionals did not negatively influence participant guidance", "AIMS : Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity , diet and physical inactivity . The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance ( IGT ) . METHODS : A total of 102 subjects were studied , r and omised into two groups . Subjects in the intervention group received regular dietary advice , and were stimulated to lose weight and to increase their physical activity . The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity . Before and after the first year , glucose tolerance was measured and several other measurements were done . RESULTS : Body weight loss after 1 y was higher in the intervention group . The 2-h blood glucose concentration decreased 0.8±0.3 mmol/l in the intervention group and increased 0.2±0.3 mmol/l in the control group ( P . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity . CONCLUSION : A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle , which improve glucose tolerance in subjects with IGT . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity ", "OBJECTIVE Individuals with impaired glucose tolerance ( IGT ) have a high risk of developing NIDDM . The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM , i.e. , reduce the incidence of NIDDM , and thereby reduce the overall incidence of diabetic complications , such as cardiovascular , renal , and retinal disease , and the excess mortality attributable to these complications . RESEARCH DESIGN AND METHODS In 1986 , 110,660 men and women from 33 health care clinics in the city of Da Qing , China , were screened for IGT and NIDDM . Of these individuals , 577 were classified ( using World Health Organization criteria ) as having IGT . Subjects were r and omized by clinic into a clinical trial , either to a control group or to one of three active treatment groups : diet only , exercise only , or diet plus exercise . Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM . Cox 's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment . RESULTS The cumulative incidence of diabetes at 6 years was 67.7 % ( 95 % CI , 59.8–75.2 ) in the control group compared with 43.8 % ( 95 % CI , 35.5–52.3 ) in the diet group , 41.1 % ( 95 % CI , 33.4–49.4 ) in the exercise group , and 46.0 % ( 95 % CI , 37.3–54.7 ) in the diet-plus-exercise group ( P relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight ( BMI baseline BMI and fasting glucose , the diet , exercise , and diet-plus-exercise interventions were associated with 31 % ( P risk of developing diabetes , respectively . CONCLUSIONS Diet and /or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "OBJECTIVES The purpose of this study was to determine the feasibility of implementing a diabetes prevention program ( DPP ) in a rural African-American church . METHODS A six-session DPP , modeled after the successful National Institutes of Health ( NIH ) DPP , was implemented in a rural African-American church . Adult members of the church identified as high risk for diabetes , based on results of a risk question naire , were screened with a fasting glucose . Persons with prediabetes , a fasting glucose of 100 - 125 mg/dL , participated in the six-session , Lifestyle Balance Church DPP . The primary outcomes were attendance rates and changes in fasting glucose , weight and body mass index measured at baseline , six- and 12-month follow-up . RESULTS Ninety-nine adult church members were screened for diabetes risk . Eleven had impaired fasting glucose . Ten of 11 participated in the six-session intervention , for an attendance rate of 78 % . After the intervention and 12-month follow-up , there was a mean weight loss of 7.9 lbs and 10.6 lbs , respectively . CONCLUSIONS This pilot project suggests that a modified six-session DPP can be translated to a group format and successfully implemented in a church setting . Further r and omized studies are needed to determine the effectiveness of such an intervention", "Aims /hypothesisTo assess the feasibility and effectiveness of an active real-life primary care lifestyle intervention in preventing type 2 diabetes within a high-risk Mediterranean population . Methods A prospect i ve cohort study was performed in the setting of Spanish primary care . White-European individuals without diabetes aged 45–75 years ( n = 2,054 ) were screened using the Finnish Diabetes Risk Score ( FINDRISC ) and a subsequent 2 h OGTT . Where feasible , high-risk individuals who were identified were allocated sequentially to st and ard care , a group-based or an individual level intervention ( intensive reinforced DE-PLAN [ Diabetes in Europe — Prevention using Lifestyle , Physical Activity and Nutritional ] intervention ) . The primary outcome was the development of diabetes according to WHO criteria . Analyses after 4-year follow-up were performed based on the intention-to-treat principle with comparison of st and ard care and the combined intervention groups . Results The st and ard care ( n = 219 ) and intensive intervention ( n = 333 ) groups were comparable in age ( 62.0/62.2 years ) , sex ( 64.4/68.2 % women ) , BMI ( 31.3/31.2 kg/m2 ) , FINDRISC score ( 16.2/15.8 points ) , fasting ( 5.3/5.2 mmol/l ) , 2 h plasma glucose ( 7.1/6.9 mmol/l ) and self-reported interest to make lifestyle changes at baseline . Diabetes was diagnosed in 124 individuals : 63 ( 28.8 % ) in the st and ard care group and 61 ( 18.3 % ) in the intensive intervention group . During a 4.2-year median follow-up , the incidences of diabetes were 7.2 and 4.6 cases per 100 person-years , respectively ( 36.5 % relative risk reduction , p number of participants needed to be treated by intensive intervention for 4 years to reduce one case of diabetes was 9.5 . Conclusions /interpretationIntensive lifestyle intervention is feasible in a primary care setting and substantially reduces diabetes incidence among high-risk individuals . Clinical trial registration : Clinical Trial.gov NCT01519505 Funding : Commission of the European Communities , Institute of Health Carlos III , Spanish Ministry of Health and Department of Health , Generalitat de Catalunya", "OBJECTIVES We tested the effectiveness of a community-based , literacy-sensitive , and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income , Spanish-speaking Latinos at increased diabetes risk . METHODS Three hundred twelve participants from Lawrence , Massachusetts , were r and omly assigned to lifestyle intervention care ( IC ) or usual care ( UC ) between 2004 and 2007 . The intervention was implemented by trained Spanish-speaking individuals from the community . Each participant was followed for 1 year . RESULTS The participants ' mean age was 52 years ; 59 % had less than a high school education . The 1-year retention rate was 94 % . Compared with the UC group , the IC group had a modest but significant weight reduction ( -2.5 vs 0.63 lb ; P = .04 ) and a clinical ly meaningful reduction in hemoglobin A1c ( -0.10 % vs -0.04 % ; P = .009 ) . Likewise , insulin resistance improved significantly in the IC compared with the UC group . The IC group also had greater reductions in percentage of calories from total and saturated fat . CONCLUSIONS We developed an inexpensive , culturally sensitive diabetes prevention program that result ed in weight loss , improved HbA1c , and improved insulin resistance in a high-risk Latino population", "Objective : The US Diabetes Prevention Program ( DPP ) and other large trials internationally have shown that an intensive lifestyle intervention can reduce the development of type 2 diabetes . We evaluated long-term effects of a lower cost , group-based adaption of the DPP lifestyle intervention offered by the YMCA . Methods : Participants were adults with BMI ≥24 kg/m2 and r and om capillary blood glucose 6.1–11.1 mmol/L who had been previously enrolled in a cluster-r and omized trial comparing a group-based DPP lifestyle intervention versus brief advice alone . Four to 12 months after completion of the initial trial , 72 % of 92 participants enrolled in an extension study , and all were offered a group lifestyle maintenance program at the YMCA . Paired t-tests were used to assess within-group changes ; ANCOVA with adjustment was used for between-group comparisons . Results : At 28 months , after both arms were offered the same 8-month lifestyle maintenance intervention , both arms had statistically significant weight losses compared to baseline ( brief advice controls : −3.6 % ; 95 % CI : −5.8 to −1.4 ; intensive lifestyle : −6.0 % ; 95 % CI : −8.8 to −3.2 ) . Participants initially assigned to the DPP also experienced significant improvements in blood pressure and total cholesterol . Discussion : The YMCA is a promising channel for dissemination of a low-cost model for lifestyle diabetes prevention . Future studies are needed to verify these findings", "Background / Objectives : To evaluate the effect of a 4.1-year ( range 3–6 years ) lifestyle intervention according to general public health recommendations on glucose tolerance and dropout in a Dutch population with impaired glucose tolerance (IGT).Subjects/ Methods : In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht , 147 Caucasian IGT subjects were r and omized to an intervention group ( INT : n=74 ; 38 male , 36 female ) and control group ( CON : n=73 ; 37 male , 36 female ) . Annually , subjects underwent measurements of body weight , anthropometry , glucose tolerance ( oral glucose tolerance test ) , insulin resistance ( homeostasis model assessment -insulin resistance ) , maximal aerobic capacity ( VO2 max ) , blood lipids and blood pressure . INT received individual advice regarding a healthy diet and physical activity . Results : INT decreased their saturated fat intake , increased their carbohydrate intake ( P and VO2 max ( P=0.04 ) compared with CON . Body weight did not change significantly ( P=0.20 ) between the groups . After an initial decrease , 2-h glucose levels overall increased in INT ( + 0.11 mmol/l ) , but significantly less than CON ( + 1.18 mmol/l ; P=0.04 ) . Diabetes incidence was lower in INT versus CON ( 30 versus 56 % , P=0.04 ) . Change in body weight was associated with change in 2-h glucose levels ( β=0.399 mmol/l per kg , P=0.02 ) . Dropouts had a lower aerobic fitness and socioeconomic status , and a higher body mass index ( BMI ) and 2-h glucose compared with non-dropouts . Conclusions : Prolonged feasible changes in diet and physical activity prevent deterioration of glucose tolerance and reduce diabetes risk . Low socioeconomic status , low aerobic fitness and high BMI and 2-h glucose are indicative of dropout to the program", "OBJECTIVE To determine whether improvements in glucose regulation following the PREPARE structured education programme were sustained at 24 months . PATIENTS AND METHODS Ninety-eight overweight or obese individuals with impaired glucose tolerance were r and omized to receive : ( 1 ) advice leaflet , ( 2 ) 3-h structured education programme aim ed at promoting physical activity , ( iii ) 3-h structured education with personalized pedometer use . The primary outcome was change in 2-h post-challenge plasma glucose . RESULTS Seventy-three ( 74 % ) individuals were included for analysis at 24 months ; age 65 ± 8 years , BMI 29.3 ± 4.8 kg/m(2 ) , South Asian ethnicity 21 % . A statistically significant reduction in 2-h glucose of -1.6 mmol/l ( -0.4 to -2.7 ) was seen in the education-with-pedometer group compared with the control group . There is no significant difference in the education-only group . CONCLUSION Improvements in glucose regulation following a pragmatic group-based structured education with pedometer use were sustained at 24 months", "BACKGROUND The Diabetes Prevention Program ( DPP ) demonstrated that lifestyle intervention reduces risk for type 2 diabetes and the metabolic syndrome . A universal framework for translation of multiple aspects of the DPP intervention , including training , support , and evaluation is needed to enhance treatment fidelity in a variety of setting s. PURPOSE This study aims to develop a comprehensive model for diabetes prevention translation using a modified DPP lifestyle intervention . METHODS The DPP lifestyle intervention was adapted to a 12-session group-based program called Group Lifestyle Balance for implementation in the community setting . A model for training and support mirroring that of the DPP was developed for prevention professionals administering the program . The process of training/support and program implementation was evaluated for feasibility and effectiveness using a nonr and omized prospect i ve design in two phases ( N=51 , Phase 1 : 2005 - 2006 ; N=42 , Phase 2 : 2007 - 2009 ; data analysis completed 2008 - 2009 ) . A total of 93 nondiabetic individuals with BMI > or=25 kg/m(2 ) and the metabolic syndrome or prediabetes participated . Measures were collected at baseline and post-intervention for all and 6 and 12 months post-intervention for Phase 2 . RESULTS Significant decreases in weight , waist circumference , and BMI were noted in both phases from baseline . Participants in Phase 2 also demonstrated decreases in total cholesterol , non-HDL cholesterol , and systolic and diastolic blood pressure that were maintained at 12 months . Average combined weight loss for both groups over the course of the 3-month intervention was 7.4 pounds ( 3.5 % relative loss , p weight loss , respectively . More than 80 % of those achieving 7 % weight loss in the Phase-2 group maintained their weight loss at 6 months . CONCLUSIONS A comprehensive diabetes prevention model for training , intervention delivery , and support was shown to be successful and was effective in reducing diabetes and cardiovascular disease risk factors in this group of high-risk individuals" ]	41182e62-06ff-11f0-808a-c43d1ab1c353
STUDY OBJECTIVE : To assess the effect of computers and computer-based clinical decision support systems on the management of hypertension . DESIGN : Systematic review of r and omised controlled trials . SETTING : Ambulatory hypertension clinics , community-based health centres , and general practice s. PARTICIPANTS : 11,962 patients enrolled in seven trials retrieved from a systematic search ( electronic data bases , contact with authors , reference lists ; no restriction on language ) . MAIN RESULTS : Individual trials report on a diverse population of patients ( newly diagnosed or established hypertensive patients ) , interventions ( computers used for case finding , recall and registration , feedback on quality of blood pressure control and prescribing information ) , and outcomes ( administration , physician performance and blood pressure control ) . Four of five trials reported an improvement in patient administration using a computer . Two of three trials reported an improvement in physician performance using a computer . Two of six trials . reported an improvement in blood pressure control in patients using a computer . However , positive findings in two trials should be regarded cautiously because of the potential effects of cluster r and omisation . CONCLUSIONS : It seems that computers have a favourable effect on the uptake and follow up of patients in hypertension management . The effect of computers on physician knowledge , recording of information , and blood pressure control in patients is less conclusive and further studies are required	[ "The authors evaluated a six-session interactive computer cognitive-behavioral treatment program given to volunteer patients who met Research Diagnostic Criteria ( RDC ) for major or minor depressive disorder . Patients were r and omly assigned to computer-administered cognitive-behavioral treatment , to therapist-administered cognitive-behavioral treatment , or to a waiting-list control condition . After treatment and at 2-month follow-up , both treatment groups had improved significantly more than control subjects in their scores on the Beck Depression Inventory , SCL-90-R depression and global scales , Hamilton Rating Scale for Depression , and Automatic Thoughts Question naire . The treatment groups did not differ from each other at either time", "OBJECTIVES This study aim ed to assess the uptake and effect in primary care of a computerized decision support system ( DSS ) for the management of hyperlipidaemia . METHOD A prospect i ve controlled trial was conducted in 25 practice s covering a population of 150,000 in the city of Birmingham . The Primed system , a specialist developed , rule based DSS for general practice , was introduced prospect ively after a 3-month baseline data collection . The main outcome measures were nine months ' data on prescribing of lipid lowering agents ; use of laboratory tests ; and referrals to secondary care for the investigation of hyperlipidaemia . RESULTS System use was lower than expected . A shift was observed towards requests for appropriate follow-up of previously abnormal lipid results and a greater emphasis on full lipid profiles , in line with the DSS guidelines . Referrals showed a 55 % decrease on those expected ( NS ) . The prescribing evaluation revealed a large variation between practice s , but no significant alteration following system use . Views of users favoured decision support as a concept , but criticised technical problems with the system . CONCLUSIONS Greater integration of DSS software and practice based data h and ling systems is needed . The mode of data capture , and hence both the content and form of knowledge representation , in DSS must take greater account of the primary care consultation process if such systems are to be of use to practitioners", "BACKGROUND Increasing indications for oral anticoagulation has led to pressure on general practice s to undertake therapeutic monitoring . Computerized decision support ( DSS ) has been shown to be effective in hospitals for improving clinical management . Its usefulness in primary care has previously not been investigated . AIM To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled , defined as within the appropriate therapeutic range of International Normalised Ratio ( INR ) . METHOD All patients receiving warfarin from two Birmingham inner city general practice s were invited to attend a practice -based anticoagulation clinic . In practice A all patients were managed using DSS . In practice B patients were r and omized to receive dosing advice either through DSS or through the local hospital laboratory . Clinical outcomes , adverse events and patient acceptability were recorded . RESULTS Forty-nine patients were seen in total . There were significant improvements in INR control from 23 % to 86 % ( P > 0.001 ) in the practice where all patients received dosing through DSS . In the practice where patients were r and omized to either DSS or hospital dosing , logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients ( P Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months ( 24 days to 36 days ) ( P = 0.033 ) . Adverse events were comparable between hospital and practice -dosed patients , although a number of esoteric events occurred . Patient satisfaction with the practice clinics was high . CONCLUSION Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control , frequency of review and general acceptability", "The hypothesis that general practitioners would obtain better outcomes for patients with hypertension using a computer than doctors not using a computer was tested . Sixty family physicians were r and omised to two treatment strategies . \" Test \" physicians completed a data collection form after each visit from a patient with hypertension and mailed the forms to the test centre for processing . Computer feedback on management was mailed to the doctors . This encouraged doctors to apply the \" stepped care \" protocol , supplied charts of diastolic blood pressure v time , and ranked patients ' diastolic blood pressures by percentile . Letters were mailed to patients to remind them of appointments . \" Control \" doctors filled out the same data collection forms as test physicians , but neither doctors nor patients received computer feedback . Physicians who used the computer saw more patients per practice than control doctors ( test 50 patients , control 40 ) . For all patients the length of follow up was significantly longer in test practice s ( test 199 days , control 167 ) , and a smaller percentage dropped out of active treatment in test practice s ( test 37.5 % , control 42.1 % ) . For patients with \" moderate \" hypertension of a baseline diastolic pressure of greater than 104 mm Hg the mean score of the last recorded pressure was below the goal of 90 mm Hg in test practice s ( 88.5 mm Hg ) , but it failed to reach this goal in control practice s ( 93.3 mm Hg ) . A greater average reduction of diastolic pressure was achieved in test practice s ( test 21.7 mm Hg , control 16.7 mm Hg ) . Though patients with \" moderate \" hypertension were better controlled in test practice s than in control practice s , the patients in test practice s visited their doctors less often ( test 13.3 visits per patient-year , control 17.4 visits ) . Among patients with newly detected hypertension test practice s achieved a greater reduction in diastolic pressure than control practice s ( test 15.1 mm Hg v control 11.3 mm Hg ) and more sustained control of hypertension ( test 323 days per patient-year with a diastolic pressure of 90 mm Hg or less v control 259 days )", "The associations of diastolic blood pressure ( DBP ) with stroke and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any \" threshold \" below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at \" baseline \" with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this \" regression dilution \" bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally \" hypertensive \" or \" normotensive \" , a lower blood pressure should eventually confer a lower risk of vascular disease", "A total of 278 hypertensive patients in three clinics were r and omly allocated to have their medical records held in a computer system ( 136 ) or on st and ard hospital notes ( 142 ) . For the computer system the doctor completed a structured input form , and the information on symptoms , physical findings , and diagnoses was more complete than that in the st and ard notes . This result ed in certain symptoms and risk factors being recognised more often when the computer system was used . The hypertension clinics ' routines were not disrupted by the introduction of a computer-held system , and follow-up consultation times were not affected by the type of records kept , although the first consultation took eight minutes longer when computer documents were completed . The patients remained in the trial for one year and clinical management was assessed from blood pressure control , drop-out rates , and the frequency of performing investigations . These estimates of management showed no significant difference between the two groups , but the attempt to tailor the computer system to help management made the system acceptable to the doctors using it . The computer system continues to be used and is providing data for research into hypertension", "To overcome shortcomings in the delivery of care for hypertension various approaches have been developed including a system whereby care of hypertension is shared in a formal manner between general practitioners and hospital specialists . The feasibility , acceptability and cost-effectiveness of a computerised model of shared care were investigated in three matched groups of patients attending hypertension clinics in Glasgow . Glasgow Blood Pressure Clinic attenders considered suitable for shared care by their consultants were r and omised to shared care ( n = 277 ) or continued clinic follow-up ; a further control group ( n = 277 ) was identified from an independent nurse-practitioner clinic . After 2 years of follow-up , feasibility was estimated by the proportion of patients who had undergone an adequate review ( blood pressure , serum creatinine and electrocardiograph ) ; acceptability to general practitioners and patients was assessed by question naires ; cost-effectiveness was calculated as the cost ( to National Health Service and patient ) per adequate review . The drop-out rate for shared care over 2 years was 3 % compared with 14 % for the outpatient clinic and 9 % for the nurse-practitioner clinic . In year 2 , rates of adequate review s were 82 % , 52 % and 75 % , respectively . Blood pressure control was similar in the groups . Of 297 general practitioners invited to participate , 85 % agreed and 68 % wished to continue participation after 2 years . About 50 % of shared care patients preferred this method of follow-up compared with their earlier experience of clinic attendance . Shared care was more cost-effective than either conventional or nurse-practitioner clinic follow-up , especially with respect to cost to the patient ; costs per adequate review ( pound sterling ) were 28.96 , 50.55 and 30.95 , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS", "Two interventions design ed to help physicians manage hypertensive patients were evaluated in a controlled trial : 1 ) computer-generated feedback to facilitate identification of poorly controlled patients ; and 2 ) a physician education program on clinical management strategies , emphasizing patient compliance . Four physician practice teams received either computer feedback , the education program , both , or neither . Feedback team physicians received seven monthly listings of the latest visits and blood pressures of their hypertensive patients . The self-administered learning program included written clinical simulations and associated didactic material . Experimental and control physicians were similar in baseline knowledge , patient mix and level of training . All feedback team physicians requested appointments for listed patients , and their patients made twice as many visits as control patients during the intervention period ( p content-specific post-intervention test : mean score 84 per cent compared with 74 per cent for the control group ( p blood pressure over the study period . However , no differences between intervention teams could be detected ( p > 0.20 ) . The probability of missing a 10 mm interteam difference in outcome diastolic pressure was 1 per cent ( power of 0.99 ) . Strategies for further improvement in outpatient hypertension management may need to come from outside the traditional medical model", "In a r and omized , controlled trial ( N = 8,298 ) the authors compared three ways of encouraging patients in a large family practice to obtain a blood pressure check . Working from computerized medical records at a teaching familymedicine center , the study included patients aged 18 years and over who had not had a blood pressure measurement during the previous year . In a normalcare control group , 21.1 % of those due for a blood pressure reading obtained one during the trial year . In one intervention group , a computer-generated message reminded the doctor to check the blood pressure of patients who happened to visit the center for an appointment ; 30.7 % of patients allocated to this group were checked . In the second group , the nurse contacted patients by telephone and encouraged 24.1 % of those who were due for a check to obtain one . Sending a letter to patients in the third group yielded a 35.7 % compliance rate . Considering the costs of the three interventions , the physician reminder was the most cost effective , followed by the letter reminder . Although statistically significant , the impact of the reminders was modest . A better approach might involve a combination of routine reminders to the physician , followed by letters to noncompliant patients", "Abstract One hundred and sixteen patients with hypertension were allocated r and omly to treatment by a computer program or by physicians . All were under the care of physicians in one of two hypertension clinics , but for computer treated patients ( C ) the program provided physicians with treatment recommendations which they were free to follow or reject whereas no recommendations were made for physician treated patients ( P ) . The computer program could use thiazide , alphamethyldopa , hydralazine or quanethidine ; physicians used whatever drugs they wished . Blood pressure ( BP ) response was similar for both groups , as were drug side effects and overt non-compliance with treatment . A computer program such as this one could guide allied health workers in setting s where expert physicians are scarce , improving large scale treatment of hypertension" ]	41182ed0-06ff-11f0-808a-c43d1ab1c353
Background Integrated care interventions for chronic conditions can lead to improved outcomes , but it is not clear when and why this is the case . This study aims to answer the following two research questions : First , what are the context , mechanisms and outcomes of integrated care for people with type 2 diabetes ? Second , what are the relationships between context , mechanisms and outcomes of integrated care for people with type 2 diabetes ? Methods A systematic literature search was conducted for the period 2003–2013 in Cochrane and PubMed . Articles were included when they focussed on integrated care and type 2 diabetes , and concerned empirical research analysing the implementation of an intervention . Data extraction was performed using a common data extraction table . The quality of the studies was assessed with the Mixed Methods Appraisal Tool . The CMO model ( context + mechanism = outcome ) was used to study the relationship between context factors ( described by the barriers and facilitators encountered in the implementation process and categorised at the six levels of the Implementation Model ) , mechanisms ( defined as intervention types and described by their number of Chronic Care Model (sub-)components ) and outcomes ( the intentional and unintentional effects triggered by mechanism and context ) . Results Thirty-two studies met the inclusion criteria . Most reported barriers to the implementation process were found at the organisational context level and most facilitators at the social context level . Due to the low number of articles reporting comparable quantitative outcome measures or in-depth qualitative information , it was not possible to make statements about the relationship between context , mechanisms and outcomes . Conclusions Efficient re source allocation should entail increased investments at the organisational context level where most barriers are expected to occur . It is likely that investments at the social context level will also help to decrease the development of barriers at the organisational context level , especially by increasing staff involvement and satisfaction . If future research is to adequately inform practice and policy regarding the impact of these efforts on health outcomes , focus on the actual relationships between context , mechanisms and outcomes should be actively incorporated into study design	[ "OBJECTIVE —The purpose of this study was to determine whether implementation of a multicomponent organizational intervention can produce significant change in diabetes care and outcomes in community primary care practice s. RESEARCH DESIGN AND METHODS —This was a group-r and omized , controlled clinical trial evaluating the practical effectiveness of a multicomponent intervention ( TRANSLATE ) in 24 practice s. The intervention included implementation of an electronic diabetes registry , visit reminders , and patient-specific physician alerts . A site coordinator facilitated previsit planning and a monthly review of performance with a local physician champion . The principle outcomes were the percentage of patients achieving target values for the composite of systolic blood pressure ( SBP ) mmHg , LDL cholesterol A1C months , 69,965 visits from 8,405 adult patients with type 2 diabetes were recorded from 238 health care providers in 24 practice s from 17 health systems . Diabetes process measures increased significantly more in intervention than in control practice s , giving net increases as follows : foot examinations 35.0 % ( P annual eye examinations 25.9 % ( P renal testing 28.5 % ( P A1C testing 8.1%(P blood pressure monitoring 3.5 % ( P = 0.05 ) ; and LDL testing 8.6 % ( P Mean A1C adjusted for age , sex , and comorbidity decreased significantly in intervention practice s ( P recommended clinical values for SBP , A1C , and LDL than control clinics ( P = 0.002 ) . CONCLUSIONS — Introduction of a multicomponent organizational intervention in the primary care setting significantly increases the percentage of type 2 diabetic patients achieving recommended clinical outcomes ", "OBJECTIVE To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population . RESEARCH DESIGN AND METHODS Five public clinics in Chicago , Illinois , participated in the study with computer kiosks installed in waiting room areas . Two hundred forty-four subjects with diabetes were r and omized to receive either supplemental computer multimedia use ( intervention ) or st and ard of care only ( control ) . The intervention includes audio/video sequences to communicate information , provide psychological support , and promote diabetes self-management skills without extensive text or complex navigation . HbA(1c ) ( A1C ) , BMI , blood pressure , diabetes knowledge , self-efficacy , self-reported medical care , and perceived susceptibility of complications were evaluated at baseline and 1 year . Computer usage patterns and implementation barriers were also examined . RESULTS Complete 1-year data were available for 183 subjects ( 75 % ) . Overall , there were no significant differences in change in A1C , weight , blood pressure , knowledge , self-efficacy , or self-reported medical care between intervention and control groups . However , there was an increase in perceived susceptibility to diabetes complications in the intervention group . This effect was greatest among subjects with lower health literacy . Within the intervention group , time spent on the computer was greater for subjects with higher health literacy . CONCLUSIONS Access to multimedia lessons result ed in an increase in perceived susceptibility to diabetes complications , particularly in subjects with lower health literacy . Despite measures to improve informational access for individuals with lower health literacy , there was relatively less use of the computer among these participants", "Objective To determine whether a diabetes case management telemedicine intervention reduced healthcare expenditures , as measured by Medicare cl aims , and to assess the costs of developing and implementing the telemedicine intervention . Design We studied 1665 participants in the Informatics for Diabetes Education and Telemedicine ( IDEATel ) , a r and omized controlled trial comparing telemedicine case management of diabetes to usual care . Participants were aged 55 years or older , and resided in federally design ated medically underserved areas of New York State . Measurements We analyzed Medicare cl aims payments for each participant for up to 60 study months from date of r and omization , until their death , or until December 31 , 2006 ( whichever happened first ) . We also analyzed study expenditures for the telemedicine intervention over six budget years ( February 28 , 2000- February 27 , 2006 ) . Results Mean annual Medicare payments ( SE ) were similar in the usual care and telemedicine groups , $ 9040 ( $ 386 ) and $ 9669 ( $ 443 ) per participant , respectively ( p>0.05 ) . Sensitivity analyses , including stratification by censored status , adjustment by enrollment site , and semi-parametric weighting by probability of dropping-out , rendered similar results . Over six budget years 28 821 participant/months of telemedicine intervention were delivered , at an estimated cost of $ 622 per participant/month . Conclusion Telemedicine case management was not associated with a reduction in Medicare cl aims in this medically underserved population . The cost of implementing the telemedicine intervention was high , largely representing special purpose hardware and software costs required at the time . Lower implementation costs will need to be achieved using lower cost technology in order for telemedicine case management to be more widely used", "& NA ; Low health literacy is more prevalent in persons with limited education , members of ethnic minorities , and those who speak English as a second language , and is associated with multiple adverse diabetes‐related health outcomes . This study examined the effectiveness of a low health literacy and culturally sensitive diabetes education program for economically and socially disadvantaged adult patients with type 2 diabetes . A pre – post prospect i ve study design was used to examine outcomes over 12 months . Outcome measures included diabetes knowledge , self‐efficacy , and self‐care , measured using reliable and valid survey tools , and A1C . Over this period of time 277 patients were enrolled in the program , with 106 participants completing survey data . At the completion of the program patients had significant improvements in diabetes knowledge ( p ( p .001 ) , and three domains of self‐care including diet ( p ( p ( p .001 ) . There were no significant improvements in the frequency of blood glucose testing ( p = .345 ) . Additionally , A1C values significantly improved 3 months after completing the program ( p = .007 ) . In conclusion , a diabetes education program design ed to be culturally sensitive and meet the needs of individuals with low health literacy improves short‐term outcomes", "IN THE EARLY 1890S , DR WILLIAM HALSTED DEVELOPED radical mastectomy for breast cancer . Surgeons performed the Halsted procedure for more than 80 years even though there was little systematic evidence for its success . Then a new breed of scholars subjected the procedure to formal methods of evaluation unknown to Halsted . The methods —r and omized controlled trials ( RCTs ) principal among them — led to a surprise : radical mastectomy had no advantage over simpler forms of treatment . This is but 1 example of the hard-won victory of evidence over belief in medicine . The pioneers of the formal evaluation of medical practice s raised questions that traditional practitioners did not welcome . But in time , formal evaluation prevailed . The pioneers developed a hierarchy of evidentiary rigor relating the design of a study to the confidence that could be placed in the findings , from the lowly , nearly valueless anecdote to the royalty of evidence , the RCT . Concurrently , a similar story of hard-won learning unfolded in the so-called quality movement . Scholars illuminated the scale and types of defects in the processes of care and the outcomes , including high rates of unscientific care , inappropriate care , geographic variations in practice , latent disagreements among specialists , and oftenunrecognized medical injury to patients . Like the pioneers of evidence -based medicine , students of medical quality were at first largely ignored , but no longer . In 1999 and 2001 , the Institute of Medicine published 2 l and mark reports on the evidence for quality failures and called urgently for re design of care systems to achieve improvements . The story could end here happily with 2 great streams of endeavor merging into a framework for conjoint action : improving clinical evidence and improving the process of care . Instead , the 2 endeavors are often in unhappy tension . Neither disputes that progress toward health care ’s main goal , the relief of illness and pain , requires research of many kinds : basic , clinical , systems , epidemiologic . The disagreement centers on epistemology — ways to get at “ truth ” and how those ways should vary depending on the knowledge sought . Individuals most involved in day-to-day improvement work fear that if “ evidence ” is too narrowly defined and the approach to gathering evidence too severely constrained , progress may be the victim . For example , the RCT is a powerful , perhaps unequaled , research design to explore the efficacy of conceptually neat components of clinical practice —tests , drugs , and procedures . For other crucially important learning purpose s , however , it serves less well . Recent controversies about the evaluation of rapid response teams provide a case in point . These controversies show the importance of adjusting research methods to fit research questions . Although only 10 % to 15 % of in patients resuscitated outside intensive care units survive to hospital discharge , early warning signs are present in a large percentage of patients who ultimately experience cardiac arrest . Rapid response team systems bring expert clinicians to the bedsides of deteriorating patients before arrest occurs . In the mid 1990s , based largely on reports from Australian investigators , the Institute for Healthcare Improvement and others began introducing the concept to willing hospitals . Local experience strongly suggested that these systems often , although not always , were associated with improved outcomes , including reduced anxiety among nursing staff ; increased interdisciplinary teamwork ; decreased cardiac arrests outside of intensive care units ; and , in some cases , declines in mortality . The evidence base took a turn in June 2005 with the publication of the Medical Early Response Intervention and Therapy ( MERIT ) Study , a cluster r and omized prospect i ve trial that cl aim ed to find no beneficial effect of these teams on several primary outcomes . Controversy has continued since then regarding the scientific evidence for rapid response systems . In fact , the MERIT trial was not negative ; it was inconclusive . The study team encountered an array of serious problems in execution , common in social science . For example , although the study ’s power calculation assumed a baseline rate of 30 events per 1000 admissions , the actual rate proved to be fewer than 7 events per 1000 admissions ; thus , the study was ef fect ively underpowered by 500 % . Crosscontamination abounded ; some control hospitals implemented rapid response protocol s , and several study", "Background Type 2 diabetes mellitus is a complex , progressive disease which requires a variety of quality improvement strategies . Limited information is available on the feasibility and effectiveness of interdisciplinary diabetes care teams ( IDCT ) operating on the interface between primary and specialty care . A first study hypothesis was that the implementation of an IDCT is feasible in a health care setting with limited tradition in shared care . A second hypothesis was that patients who make use of an IDCT would have significantly better outcomes compared to non-users of the IDCT after an 18-month intervention period . A third hypothesis was that patients who used the IDCT in an Advanced quality Improvement Program ( AQIP ) would have significantly better outcomes compared to users of a Usual Quality Improvement Program ( UQIP ) . Methods This investigation comprised a two-arm cluster r and omized trial conducted in a primary care setting in Belgium . Primary care physicians ( PCPs , n = 120 ) and their patients with type 2 diabetes mellitus ( n = 2495 ) were included and subjects were r and omly assigned to the intervention arms . The IDCT acted as a cornerstone to both the intervention arms , but the number , type and intensity of IDCT related interventions varied depending upon the intervention arm . Results Final registration included 67 PCPs and 1577 patients in the AQIP and 53 PCPs and 918 patients in the UQIP . 84 % of the PCPs made use of the IDCT . The expected participation rate in patients ( 30 % ) was not attained , with 12,5 % of the patients using the IDCT . When comparing users and non-users of the IDCT ( irrespective of the intervention arm ) and after 18 months of intervention the use of the IDCT was significantly associated with improvements in HbA1c , LDL-cholesterol , an increase in statins and anti-platelet therapy as well as the number of targets that were reached . When comparing users of the IDCT in the two intervention arms no significant differences were noted , except for anti-platelet therapy . Conclusion IDCT 's operating on the interface between primary and specialty care are associated with improved outcomes of care . More research is required on what team and program characteristics contribute to improvements in diabetes care . Trial registration NTR 1369", "Background Most research publications on Chronic Care Model ( CCM ) implementation originate from organizations or countries with a well-structured primary health care system . Information about efforts made in countries with a less well-organized primary health care system is scarce . In 2003 , the Belgian National Institute for Health and Disability Insurance commissioned a pilot study to explore how care for type 2 diabetes patients could be organized in a more efficient way in the Belgian healthcare setting , a setting where the organisational framework for chronic care is mainly hospital-centered . Methods Process evaluation of an action research project ( 2003–2007 ) guided by the CCM in a well-defined geographical area with 76,826 inhabitants and an estimated number of 2,300 type 2 diabetes patients . In consultation with the region a program for type 2 diabetes patients was developed . The degree of implementation of the CCM in the region was assessed using the Assessment of Chronic Illness Care survey ( ACIC ) . A multi method approach was used to evaluate the implementation process . The result ing data were triangulated in order to identify the main facilitators and barriers encountered during the implementation process . Results The overall ACIC score improved from 1.45 ( limited support ) at the start of the study to 5.5 ( basic support ) at the end of the study . The establishment of a local steering group and the appointment of a program manager were crucial steps in strengthening primary care . The willingness of a group of well-trained and motivated care providers to invest in quality improvement was an important facilitator . Important barriers were the complexity of the intervention , the lack of quality data , inadequate information technology support , the lack of commitment procedures and the uncertainty about sustainable funding . Conclusion Guided by the CCM , this study highlights the opportunities and the bottlenecks for adapting chronic care delivery in a primary care system with limited structure . The study succeeded in achieving a considerable improvement of the overall support for diabetes patients but further improvement requires a shift towards system thinking among policy makers . Currently primary care providers lack the opportunities to take up full responsibility for chronic care . Trial registration number Clinical Trials.gov Identifier :", " This article describes the design and implementation of an online diabetes self-management intervention for a sample of inner-city African Americans with diabetes . Study participants were r and omly assigned to the treatment ( 26 ) and control ( 21 ) conditions . The results indicate that treatment group participants were more likely to achieve positive outcomes in terms of lowered hemoglobin A1c and body mass index measurements than were control group members . These findings support the development of telehealth interventions to promote effective chronic disease management in medically underserved communities", "Background : With growing use of Community Health Workers ( CHWs ) to reach underserved population s , there is a need for more information on training methods to prepare CHWs , particularly in a health educator role . Objectives : To describe procedures used to recruit , train , and evaluate CHWs in Project Sugar 2 , a r and omized controlled trial of a nurse case manager and CHW team intervention design ed to improve diabetes care and control in a sample of 542 urban African Americans with type 2 diabetes . Methods : CHWs received a Core Training on guidelines and procedures , didactic diabetes self-management education , and research protocol training . However , barriers to CHW implementation of the intervention were encountered , including CHW attrition , job performance and satisfaction issues , low self-confidence in knowledge and skills as educators , difficulties with maintaining a large caseload , and inefficiencies experienced in conducting home visits . To address barriers , the initial training was modified and Results : The supplemental training result ed in CHW retention , satisfaction , confidence in skills , and feelings of ownership of the intervention . Participant satisfaction with care received from the CHWs and the Project Sugar 2 intervention was rated as high by 97 % and 93 % of responders , respectively . Conclusion : Core training in research intervention policies , procedures , and protocol s , combined with an extended participatory training , led to effective preparation of laypersons to serve as CHWs", "We studied the impact of nurse case management ( NCM ) on blood pressure ( BP ) , hemoglobin A1C , lipids , and diabetes complication screening . A 1-year r and omized-controlled trial was conducted in two primary care clinics of the Penn State Hershey Medical Center . Diabetes patients were r and omized to control group ( CG ) ( n=182 ) who received usual care by their primary care provider and intervention group ( IG ) ( n=150 ) who received additional NCM care , including self-management education , and implementation of diabetes guidelines . Primary outcomes included BP , A1C , lipid , process measures , and secondary outcome was diabetes-related emotional distress as assessed by Problem Areas in Diabetes ( PAID ) . BP significantly decreased from 137/77 to 129/72 in IG as compared to an increase from 136/77 to 138/79 in CG after 1 year . PAID scores improved significantly in IG ( from 23 to 10 ) due to reduced emotional stress . A1C ( 7.4 ) and LDL ( 105 ) were unaffected . Complications screening significantly improved in IG compared to CG : opthalmologic exam 26 to 68 % , foot exam 47 to 64 % , and nephropathy screening 34 to 72 % . NCM improved BP , diabetes-related emotional distress , and process measures in primary care . Unchanged A1C and lipids might be due to a threshold effect . Intervention based upon initial risk assessment may prove more cost-effective ", "M eeting the complex needs of patients with chronic illness or impairment is the single greatest challenge facing organized medical practice . Usual care is not doing the job ; dozens of surveys and audits have revealed that sizable proportions of chronically ill patients are not receiving effective therapy , have poor disease con- trol , and are unhappy with their care ( 1 ) . Results of r and omized trials also show that effective disease management programs can achieve substantially better outcomes than usual care , the control intervention . These trials , along with the ideas and efforts for improvement discussed in this issue , show that we can improve care and outcomes . As the articles suggest , these improvements will not come easily . If we are to improve care for most patients with chronic illness , the evidence strongly suggests that we reshape our ambulatory care systems for this purpose . Pri- mary care practice was largely design ed to provide ready access and care to patients with acute , varied problems , with an emphasis on triage and patient flow ; short appointments ; diagnosis and treatment of symptoms and signs ; reliance on laborato- ry investigations and prescriptions ; brief , didactic patient education ; and patient- initiated follow-up . Patients and families struggling with chronic illness have differ- ent needs , and these needs are unlikely to be met by an acute care organization and culture . They require planned , regular interactions with their caregivers , with a focus on function and prevention of exacerbations and complications . This interac- tion includes systematic assessment s , attention to treatment guidelines , and behav- iorally sophisticated support for the patient 's role as self-manager . These interactions must be linked through time by clinical ly relevant information systems and continu- ing follow-up initiated by the medical practice . Comprehensive System", "OBJECTIVE To determine the effectiveness of a provider-based education and implementation intervention for improving diabetes control . DESIGN Cluster-r and omized trial with baseline and follow-up cross sections of diabetes patients in each participating physician 's practice . SETTING Eleven US Southeastern states , 2006 - 08 . PARTICIPANTS Two hundred and five rural primary care physicians . INTERVENTION Multi-component interactive intervention including Web-based continuing medical education , performance feedback and quality improvement tools . Primary Outcome Measures ' Acceptable control ' [ hemoglobin A1c ≤9 % , blood pressure ( BP ) ] and ' optimal control ' ( A1c 364 physicians attempting to register , 205 were r and omized to the intervention ( n= 102 ) or control arms ( n= 103 ) . Baseline and follow-up data were provided by 95 physicians ( 2127 patients ) . The proportion of patients with A1c ≤9 % was similar at baseline and follow-up in both the control [ adjusted odds ratio ( AOR ) : 0.94 ; 95 % confidence interval ( CI ) : 0.61 , 1.47 ] and intervention arms [ AOR : 1.16 ( 95 % CI : 0.80 , 1.69 ) ] ; BP and LDL 130 mg/dl were also similar at both measurement points ( P= 0.66 , P= 0.46 ; respectively ) . We observed no significant effect on diabetes control attributable to the intervention for any of the primary outcome measures . Intervention physicians engaged with the Website over a median of 64.7 weeks [ interquartile range ( IQR ) : 45.4 - 81.8 ) for a median total of 37 min ( IQR : 16 - 66 ) . CONCLUSIONS A wide-reach , low-intensity , Web-based interactive multi-component intervention did not improve control of glucose , BP or lipids for patients with diabetes of physicians practicing in the rural Southeastern US" ]	41182f52-06ff-11f0-808a-c43d1ab1c353
Background Electronic health ( e-Health ) interventions are emerging as an effective alternative model for improving secondary prevention of coronary artery disease ( CAD ) . The aim of this study was to describe the effectiveness of different modes of delivery and components in e-Health secondary prevention programmes on adherence to treatment , modifiable CAD risk factors and psychosocial outcomes for patients with CAD . Method A systematic review was carried out based on articles found in MEDLINE , CINAHL , and Embase . Studies evaluating secondary prevention e-Health programmes provided through mobile-Health ( m-Health ) , web-based technology or a combination of m-Health and web-based technology were eligible . The main outcomes measured were adherence to treatment , modifiable CAD risk factors and psychosocial outcomes . The quality appraisal of the studies included was conducted using the Joanna Briggs Institute critical appraisal tool for RCT . The results were synthesis ed narratively . Result A total of 4834 titles were identified and 1350 were screened for eligibility . After review ing 123 articles in full , 24 RCTs including 3654 participants with CAD were included . Eight studies delivered secondary prevention programmes through m-Health , nine through web-based technology , and seven studies used a combination of m-Health and web-based technology . The majority of studies employed two or three secondary prevention components , of which health education was employed in 21 studies . The m-Health programmes reported positive effects on adherence to medication . Most studies evaluating web-based technology programmes alone or in combination with m-Health also utilised traditional CR , and reported improved modifiable CAD risk factors . The quality appraisal showed a moderate method ological quality of the studies . Conclusion Evidence exists that supports the use of e-Health interventions for improving secondary prevention of CAD . However , a comparison across studies highlighted a wide variability of components and outcomes within the different modes of delivery . High quality trials are needed to define the most efficient mode of delivery and components capable of addressing a favourable outcome for patients .Trial registration Not applicable	[ "AIMS AND OBJECTIVES To compare drug adherence to lipid-lowering therapy among out patients with coronary artery disease who received information via short message service , via short message service and Micro Letter , or via phone only . BACKGROUND Messaging applications and short message service are commonly used internationally . However , little is known about how coronary artery disease out patients in China may benefit from receiving health education through these technologies . DESIGN R and om sampling method . METHODS Data were collected from March-December 2013 . Subjects from Chengdu City , China , were r and omised to three groups : short message service , short message service + Micro Letter , and phone ( control ) . Appointment reminders and health information were delivered to patients in accordance with design ations . After six months , adherence to statin prescriptions was compared among the groups by using the Morisky Medication Adherence Scale . Logistic regression analysis was applied to determine those independent variables that were related to adherence . RESULTS The short message service and short message service + Micro Letter groups had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) after six months than phone group , and the short message service + Micro Letter group had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) than the short message service group . Female sex , older age and marriage show positive associations with adherence . CONCLUSIONS Short message service and messaging applications , such as Micro Letter , are effective means of providing discharged patients with reminders and coronary artery disease-related health information . Implementation of a short message service + Micro Letter program can improve outpatient adherence to medication . RELEVANCE TO CLINICAL PRACTICE This research offers useful information to help medical staff design effective interventions to improve medication compliance among coronary artery disease patients", "Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services", "Background : The CardioFit internet-based expert system was design ed to promote physical activity in patients with coronary heart disease ( CHD ) who were not participating in cardiac rehabilitation . Design : This r and omized controlled trial compared CardioFit to usual care to assess its effects on physical activity following hospitalization for acute coronary syndromes . Methods : A total of 223 participants were recruited at the University of Ottawa Heart Institute or London Health Sciences Centre and r and omly assigned to either CardioFit ( n = 115 ) or usual care ( n = 108 ) . The CardioFit group received a personally tailored physical-activity plan upon discharge from the hospital and access to a secure website for activity planning and tracking . They completed five online tutorials over a 6-month period and were in email contact with an exercise specialist . Usual care consisted of physical activity guidance from an attending cardiologist . Physical activity was measured by pedometer and self-reported over a 7-day period , 6 and 12 months after r and omization . Results : The CardioFit internet-based physical activity expert system significantly increased objective ly measured ( p = 0.023 ) and self-reported physical activity ( p = 0.047 ) compared to usual care . Emotional ( p = 0.038 ) and physical ( p = 0.031 ) dimensions of heart disease health-related quality of life were also higher with CardioFit compared to usual care . Conclusions : Patients with CHD using an internet-based activity prescription with online coaching were more physically active at follow up than those receiving usual care . Use of the CardioFit program could extend the reach of rehabilitation and secondary -prevention services", "Objective To investigate whether an internet based , nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinical ly manifest vascular disease . Design Prospect i ve r and omised controlled trial . Setting Multicentre trial in secondary and tertiary healthcare setting . Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary , cerebral , or peripheral arteries and with at least two treatable risk factors not at goal . Intervention Personalised website with an overview and actual status of patients ’ risk factors and mail communication via the website with a nurse practitioner for 12 months ; the intervention combined self management support , monitoring of disease control , and drug treatment . Main outcome measures The primary endpoint was the relative change in Framingham heart risk score after 1 year . Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor . Results Participants ’ mean age was 59.9 ( SD 8.4 ) years , and most patients ( n=246 ; 75 % ) were male . After 1 year , the relative change in Framingham heart risk score of the intervention group compared with the usual care group was −14 % ( 95 % confidence interval −25 % to −2 % ) . At baseline , the Framingham heart risk score was higher in the intervention group than in the usual care group ( 16.1 ( SD 10.6 ) v 14.0 ( 10.5 ) ) , so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score . This produced a relative change of −12 % ( −22 % to −3 % ) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and −8 % ( −18 % to 2 % ) adjusted for the baseline score . Of the individual risk factors , a difference between groups was observed in low density lipoprotein cholesterol ( −0.3 , −0.5 to −0.1 , mmol/L ) and smoking ( −7.7 % , −14.9 % to −0.4 % ) . Some other risk factors tended to improve ( body mass index , triglycerides , systolic blood pressure , renal function ) or tended to worsen ( glucose concentration , albuminuria ) . Conclusion An internet based , nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease . Trial registration Clinical trials NCT00785031", "Background The purpose of this study was to evaluate the effect of a physical activity telemonitoring program on daily physical activity level , oxygen uptake capacity ( VO2peak ) , and cardiovascular risk profile in coronary artery disease ( CAD ) patients who completed phase II cardiac rehabilitation ( CR ) . Methods Eighty CAD patients who completed phase II CR were r and omly assigned to an additional telemonitoring intervention or st and ard CR . The patients in the intervention group ( n = 40 ) wore a motion sensor continuously for 18 weeks . Each week these patients received a step count goal , with the aim to gradually increase the patients ’ physical activity level . In the control group ( n = 40 ) , the patients wore an unreadable motion sensor for seven days for measurement purpose s only ( at start of follow-up , and after six and 18 weeks ) . At start of follow-up and after 18 weeks blood lipid profile , glycemic control , waist circumference and body mass index was assessed . VO2peak was assessed at start of follow-up , and after six and 18 weeks . Re-hospitalisation rate was followed during this timeframe . Results In the intervention group , VO2peak increased significantly during follow-up ( P = 0.001 ) , in the control group it did not ( P = 0.273 ) . A significant correlation was found between daily aerobic step count and improvement in VO2peak ( P = 0.030 , r = 0.47 ) . Kaplan-Meier curve analysis showed a trend towards fewer re-hospitalisations for patients in the telemonitoring group ( P = 0.09 ) . Conclusions The study showed that , to maintain exercise tolerance and lower re-hospitalisation rate after hospital-based CR in CAD patients , a physical activity telemonitoring program might be an effective intervention", "Background Angina affects more than 50 million people worldwide . Secondary prevention interventions such as cardiac rehabilitation are not widely available for this population . An Internet-based version could offer a feasible alternative . Objective Our aim was to examine the effectiveness of a Web-based cardiac rehabilitation program for those with angina . Methods We conducted a r and omized controlled trial , recruiting those diagnosed with angina from general practitioners ( GPs ) in primary care to an intervention or control group . Intervention group participants were offered a 6-week Web-based rehabilitation program ( “ ActivateYourHeart ” ) . The program was introduced during a face-to-face appointment and then delivered via the Internet ( no further face-to-face contact ) . The program contained information about the secondary prevention of coronary heart disease ( CHD ) and set each user goals around physical activity , diet , managing emotions , and smoking . Performance against goals was review ed throughout the program and goals were then reset/modified . Participants completed an online exercise diary and communicated with rehabilitation specialists through an email link/synchronized chat room . Participants in the control group continued with GP treatment as usual , which consisted of being placed on a CHD register and attending an annual review . Outcomes were measured at 6-week and 6-month follow-ups during face-to-face assessment s. The primary outcome measure was change in daily steps at 6 weeks , measured using an accelerometer . Secondary outcome measures were energy expenditure ( EE ) , duration of sedentary activity ( DSA ) , duration of moderate activity ( DMA ) , weight , diastolic/systolic blood pressure , and body fat percentage . Self-assessed question naire outcomes included fat/fiber intake , anxiety/depression , self-efficacy , and quality of life ( QOL ) . Results A total of 94 participants were recruited and r and omized to the intervention ( n=48 ) or the usual care ( n=46 ) group ; 84 and 73 participants completed the 6-week and 6-month follow-ups , respectively . The mean number of log-ins to the program was 18.68 ( SD 13.13 , range 1 - 51 ) , an average of 3 log-ins per week per participant . Change in daily steps walked at the 6-week follow-up was + 497 ( SD 2171 ) in the intervention group and –861 ( SD 2534 ) in the control group ( 95 % CI 263 - 2451 , P=.02 ) . Significant intervention effects were observed at the 6-week follow-up in EE ( + 43.94 kcal , 95 % CI 43.93 - 309.98 , P=.01 ) , DSA ( –7.79 minutes , 95 % CI –55.01 to –7.01 , P=.01 ) , DMA ( + 6.31 minutes , 95 % CI 6.01 - 51.20 , P=.01 ) , weight ( –0.56 kg , 95 % CI –1.78 to –0.15 , P=.02 ) , self-efficacy ( 95 % CI 0.30 - 4.79 , P=.03 ) , emotional QOL score ( 95 % CI 0.01 - 0.54 , P=.04 ) , and angina frequency ( 95 % CI 8.57 - 35.05 , P=.002 ) . Significant benefits in angina frequency ( 95 % CI 1.89 - 29.41 , P=.02 ) and social QOL score ( 95 % CI 0.05 - 0.54 , P=.02 ) were also observed at the 6-month follow-up . Conclusions An Internet-based secondary prevention intervention could be offered to those with angina . A larger pragmatic trial is required to provide definitive evidence of effectiveness and cost-effectiveness . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 90110503 ; http://www.controlled-trials.com/IS RCT N90110503/IS RCT N90110503 ( Archived by WebCite at http://www.webcitation.org/6RYVOQFKM )", "Background Patients with cardiovascular diseases managed by a person-centered care ( PCC ) approach have been observed to have better treatment outcomes and satisfaction than with traditional care . eHealth may facilitate the often slow transition to more person-centered health care by increasing patients ’ beliefs in their own capacities ( self-efficacy ) to manage their care trajectory . eHealth is being increasingly used , but most studies continue to focus on health care professionals ’ logic of care . Knowledge is lacking regarding the effects of an eHealth tool on self-efficacy when combined with PCC for patients with chronic heart diseases . Objective The objective of our study was to investigate the effect of an eHealth diary and symptom-tracking tool in combination with PCC for patients with acute coronary syndrome ( ACS ) . Methods This was a sub study of a r and omized controlled trial investigating the effects of PCC in patients hospitalized with ACS . In total , 199 patients with ACS aged were r and omly assigned to a PCC intervention ( n=94 ) or st and ard treatment ( control group , n=105 ) and were followed up for 6 months . Patients in the intervention arm could choose to use a Web-based or mobile-based eHealth tool , or both , for at least 2 months after hospital discharge . The primary end point was a composite score of changes in general self-efficacy , return to work or prior activity level , and rehospitalization or death 6 months after discharge . Results Of the 94 patients in the intervention arm , 37 ( 39 % ) used the eHealth tool at least once after the index hospitalization . Most of these ( 24/37 , 65 % ) used the mobile app and not the Web-based app as the primary source of daily self-rating input . Patients used the eHealth tool a mean of 38 times during the first 8 weeks ( range 1–118 , SD 33 ) and 64 times over a 6-month period ( range 1–597 , SD 104 ) . Patients who used the eHealth tool in combination with the PCC intervention had a 4-fold improvement in the primary end point compared with the control group ( odds ratio 4.0 , 95 % CI 1.5–10.5 ; P=.005 ) . This improvement was driven by a significant increase in general self-efficacy compared with the control group ( P=.011 ) . Patients in the PCC group who did not use the eHealth tool ( n=57 ) showed a nonsignificant composite score improvement compared with those in the control group ( n=105 ) ( odds ratio 2.0 , 95 % CI 0.8–5.2 ; P=.14 ) . Conclusions We found a significant effect on improved general self-efficacy and the composite score for patients using an eHealth diary and symptom-tracking tool in combination with PCC compared with traditional care . Trial Registration Swedish registry , Research web.org , ID NR 65 791", "Objective Cardiac rehabilitation ( CR ) is pivotal in preventing recurring events of myocardial infa rct ion ( MI ) . This study aims to investigate the effect of a smartphone-based home service delivery ( Care Assessment Platform ) of CR ( CAP-CR ) on CR use and health outcomes compared with a traditional , centre-based programme ( TCR ) in post-MI patients . Methods In this unblinded r and omised controlled trial , post-MI patients were r and omised to TCR ( n=60 ; 55.7±10.4 years ) and CAP-CR ( n=60 ; 55.5±9.6 years ) for a 6-week CR and 6-month self-maintenance period . CAP-CR , delivered in participants ’ homes , included health and exercise monitoring , motivational and educational material delivery , and weekly mentoring consultations . CAP-CR uptake , adherence and completion rates were compared with TCR using intention-to-treat analyses . Changes in clinical outcomes ( modifiable lifestyle factors , biomedical risk factors and health-related quality of life ) across baseline , 6 weeks and 6 months were compared within , and between , groups using linear mixed model regression . Results CAP-CR had significantly higher uptake ( 80 % vs 62 % ) , adherence ( 94 % vs 68 % ) and completion ( 80 % vs 47 % ) rates than TCR ( p improvements in 6-minute walk test from baseline to 6 weeks ( TCR : 537±86–584±99 m ; CAP-CR : 510±77–570±80 m ) , which was maintained at 6 months . CAP-CR showed slight weight reduction ( 89±20–88±21 kg ) and also demonstrated significant improvements in emotional state ( K10 : median ( IQR ) 14.6 ( 13.4–16.0 ) to 12.6 ( 11.5–13.8 ) ) , and quality of life ( EQ5D-Index : median ( IQR ) 0.84 ( 0.8–0.9 ) to 0.92 ( 0.9–1.0 ) ) at 6 weeks . Conclusions This smartphone-based home care CR programme improved post-MI CR uptake , adherence and completion . The home-based CR programme was as effective in improving physiological and psychological health outcomes as traditional CR . CAP-CR is a viable option towards optimising use of CR services . Trial registration number ANZCTR12609000251224", "The aim of this study was to assess whether our online closed community heart care support group and information re source could sustain changes in health behaviour after the moderators withdrew their support . Heart patients ( n = 108 ) living in a deprived area of Greater Manchester were recruited from general practitioners ' coronary heart disease registries . The sample for this r and omized controlled trial was divided in half at r and om where half of the participants received password-protected access to our health portal and the other half did not . At 6 months follow-up ( based on the moderated phase ) , there was a significant difference between the experimental group and the controls in terms of self-reported diet ( eating bad foods less often ) . This change in behaviour was not sustained during the 3-month unmoderated phase . During this unmoderated phase of the intervention , the experimental group had significantly more health care visits compared with the controls . There was no significant difference between the two phases for either group in terms of exercise , smoking or social support . This study offers insight into the potential implication s for health changes of moderating arrangements for online health communities", "Background Mobile technology has the potential to deliver behavior change interventions ( mHealth ) to reduce coronary heart disease ( CHD ) at modest cost . Previous studies have focused on single behaviors ; however , cardiac rehabilitation ( CR ) , a component of CHD self-management , needs to address multiple risk factors . Objective The aim was to investigate the effectiveness of a mHealth-delivered comprehensive CR program ( Text4Heart ) to improve adherence to recommended lifestyle behaviors ( smoking cessation , physical activity , healthy diet , and nonharmful alcohol use ) in addition to usual care ( traditional CR ) . Methods A 2-arm , parallel , r and omized controlled trial was conducted in New Zeal and adults diagnosed with CHD . Participants were recruited in-hospital and were encouraged to attend center-based CR ( usual care control ) . In addition , the intervention group received a personalized 24-week mHealth program , framed in social cognitive theory , sent by fully automated daily short message service ( SMS ) text messages and a supporting website . The primary outcome was adherence to healthy lifestyle behaviors measured using a self-reported composite health behavior score ( ≥3 ) at 3 and 6 months . Secondary outcomes included clinical outcomes , medication adherence score , self-efficacy , illness perceptions , and anxiety and /or depression at 6 months . Baseline and 6-month follow-up assessment s ( unblinded ) were conducted in person . Results Eligible patients ( N=123 ) recruited from 2 large metropolitan hospitals were r and omized to the intervention ( n=61 ) or the control ( n=62 ) group . Participants were predominantly male ( 100/123 , 81.3 % ) , New Zeal and European ( 73/123 , 59.3 % ) , with a mean age of 59.5 ( SD 11.1 ) years . A significant treatment effect in favor of the intervention was observed for the primary outcome at 3 months ( AOR 2.55 , 95 % CI 1.12 - 5.84 ; P=.03 ) , but not at 6 months ( AOR 1.93 , 95 % CI 0.83 - 4.53 ; P=.13 ) . The intervention group reported significantly greater medication adherence score ( mean difference : 0.58 , 95 % CI 0.19 - 0.97 ; P=.004 ) . The majority of intervention participants reported reading all their text messages ( 52/61 , 85 % ) . The number of visits to the website per person ranged from zero to 100 ( median 3 ) over the 6-month intervention period . Conclusions A mHealth CR intervention plus usual care showed a positive effect on adherence to multiple lifestyle behavior changes at 3 months in New Zeal and adults with CHD compared to usual care alone . The effect was not sustained to the end of the 6-month intervention . A larger study is needed to determine the size of the effect in the longer term and whether the change in behavior reduces adverse cardiovascular events . Trial Registration ACTRN 12613000901707 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=364758&is Review = true ( Archived by WebCite at http://www.webcitation.org/6c4qhcHKt", "Background Cardiac telerehabilitation has been introduced as an adjunct or alternative to conventional center-based cardiac rehabilitation to increase its long-term effectiveness . However , before large-scale implementation and reimbursement in current health care systems is possible , well- design ed studies on the effectiveness of this new additional treatment strategy are needed . Objective The aim of this trial was to assess the medium-term effectiveness of an Internet-based , comprehensive , and patient-tailored telerehabilitation program with short message service ( SMS ) texting support for cardiac patients . Methods This multicenter r and omized controlled trial consisted of 140 cardiac rehabilitation patients r and omized ( 1:1 ) to a 24-week telerehabilitation program in combination with conventional cardiac rehabilitation ( intervention group ; n=70 ) or to conventional cardiac rehabilitation alone ( control group ; n=70 ) . In the telerehabilitation program , initiated 6 weeks after the start of ambulatory rehabilitation , patients were stimulated to increase physical activity levels . Based on registered activity data , they received semiautomatic telecoaching via email and SMS text message encouraging them to gradually achieve predefined exercise training goals . Patient-specific dietary and /or smoking cessation advice was also provided as part of the telecoaching . The primary endpoint was peak aerobic capacity ( VO2 peak ) . Secondary endpoints included accelerometer-recorded daily step counts , self-assessed physical activities by International Physical Activity Question naire ( IPAQ ) , and health-related quality of life ( HRQL ) assessed by the HeartQol question naire at baseline and at 6 and 24 weeks . Results Mean VO2 peak increased significantly in intervention group patients ( n=69 ) from baseline ( mean 22.46 , SD 0.78 mL/[minkg ] ) to 24 weeks ( mean 24.46 , SD 1.00 mL/[minkg ] , P of aerobic capacity confirmed a significant difference between the intervention group and control group in favor of the intervention group ( P self-reported physical activity improved more in the intervention group compared to the control group ( P=.01 ) as did the global HRQL score ( P=.01 ) . Conclusions This study showed that an additional 6-month patient-specific , comprehensive telerehabilitation program can lead to a bigger improvement in both physical fitness ( VO2 peak ) and associated HRQL compared to center-based cardiac rehabilitation alone . These results are supportive in view of possible future implementation in st and ard cardiac care", "IMPORTANCE Cardiovascular disease prevention , including lifestyle modification , is important but underutilized . Mobile health strategies could address this gap but lack evidence of therapeutic benefit . OBJECTIVE To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors . DESIGN AND SETTING The Tobacco , Exercise and Diet Messages ( TEXT ME ) trial was a parallel-group , single-blind , r and omized clinical trial that recruited 710 patients ( mean age , 58 [ SD , 9.2 ] years ; 82 % men ; 53 % current smokers ) with proven coronary heart disease ( prior myocardial infa rct ion or proven angiographically ) between September 2011 and November 2013 from a large tertiary hospital in Sydney , Australia . INTERVENTIONS Patients in the intervention group ( n = 352 ) received 4 text messages per week for 6 months in addition to usual care . Text messages provided advice , motivational reminders , and support to change lifestyle behaviors . Patients in the control group ( n=358 ) received usual care . Messages for each participant were selected from a bank of messages according to baseline characteristics ( eg , smoking ) and delivered via an automated computerized message management system . The program was not interactive . MAIN OUTCOMES AND MEASURES The primary end point was low-density lipoprotein cholesterol ( LDL-C ) level at 6 months . Secondary end points included systolic blood pressure , body mass index ( BMI ) , physical activity , and smoking status . RESULTS At 6 months , levels of LDL-C were significantly lower in intervention participants , with concurrent reductions in systolic blood pressure and BMI , significant increases in physical activity , and a significant reduction in smoking . The majority reported the text messages to be useful ( 91 % ) , easy to underst and ( 97 % ) , and appropriate in frequency ( 86 % ) . [ table : see text ] . CONCLUSIONS AND RELEVANCE Among patients with coronary heart disease , the use of a lifestyle-focused text messaging service compared with usual care result ed in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors . The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12611000161921", "Background : Medication non-adherence leads to a vast range of negative outcomes in patients with coronary artery disease . An automated web-based system managing short message service ( SMS ) reminders is a telemedicine approach to optimise adherence among patients who frequently forget to take their medications or miss the timing . Aim : This paper sought to investigate the effect of automated SMS-based reminders on medication adherence in patients after hospital discharge following acute coronary syndrome ( ACS ) . Methods : An interventional study was conducted at a tertiary teaching hospital in Malaysia . A total of 62 patients with ACS were equally r and omised to receive either automated SMS reminders before every intake of cardiac medications or only usual care within eight weeks after discharge . The primary outcome was adherence to cardiac medications . Secondary outcomes were the heart functional status , and ACS-related hospital readmission and death rates . Results : There was a higher medication adherence level in the intervention group rather than the usual care group , ( χ2 (2)=18.614 , p of being low adherent among the control group was 4.09 times greater than the intervention group ( relative risk = 4.09 , 95 % confidence interval ( CI ) 1.82–9.18 ) . A meaningful difference was found in heart functional status between the two study groups with better results among patients who received SMS reminders , ( χ2 ( 1 ) = 16.957 , p automated SMS-based reminder system can potentially enhance medication adherence in ACS patients during the early post-discharge period", "Background Mobile phone text message interventions are used to support behaviour change including physical activity , but we have less insight into how these interventions work and what factors predict response . Aims To study the effect of TEXT ME ( Tobacco EXercise and dieT Messages ) text message intervention on physical activity domains , consistency of effects across sub-groups and its additive value in patients that received traditional cardiac rehabilitation programme . Methods This is a secondary analysis of the TEXT ME , a r and omized clinical trial of lifestyle-focused text message intervention compared with usual care in patients with coronary heart disease . A quarter of the messages were design ed specifically to encourage physical activity . Sedentary time and physical activity were assessed using the Global Physical Activity Question naire . Results At baseline , 85 % of the 710 participants reported low physical activity levels . At six months , compared with controls , the intervention arm reported higher recreational physical activity ( 471 vs. 307 metabolic equivalent-min/week , p = 0.001 ) and travel physical activity ( 230 vs. 128 MET-min/week , p = 0.002 ) , similar work-related physical activity and lower sedentary times ( 494 vs. 587 min , p baseline physical activity , cardiac rehabilitation participation and text message intervention predicted physically active status at six months . Subjects that received both cardiac rehabilitation and text messaging intervention were more likely to achieve target physical activity levels compared with cardiac rehabilitation alone ( odds ratio 7.07 vs. 1.80 , p TEXT ME intervention improved recreational and travel physical activity , reduced sedentary times but had no effects on work-related physical activity . It had incremental benefits at achieving target physical activity levels even in patients participating in the traditional cardiac rehabilitation programme", "BACKGROUND Patients with myocardial infa rct ion ( MI ) seldom reach recommended targets for secondary prevention . This study evaluated a smartphone application ( \" app \" ) aim ed at improving treatment adherence and cardiovascular lifestyle in MI patients . DESIGN Multicenter , r and omized trial . METHODS A total of 174 ticagrelor-treated MI patients were r and omized to either an interactive patient support tool ( active group ) or a simplified tool ( control group ) in addition to usual post-MI care . Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence , defined as a combination of adherence failure events ( 2 missed doses registered in 7-day cycles ) and treatment gaps ( 4 consecutive missed doses ) . Secondary end points included change in cardiovascular risk factors , quality of life ( European Quality of Life-5 Dimensions ) , and patient device satisfaction ( System Usability Scale ) . RESULTS Patient mean age was 58 years , 81 % were men , and 21 % were current smokers . At 6 months , greater patient-registered drug adherence was achieved in the active vs the control group ( nonadherence score : 16.6 vs 22.8 [ P = .025 ] ) . Numerically , the active group was associated with higher degree of smoking cessation , increased physical activity , and change in quality of life ; however , this did not reach statistical significance . Patient satisfaction was significantly higher in the active vs the control group ( system usability score : 87.3 vs 78.1 [ P = .001 ] ) . CONCLUSIONS In MI patients , use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life . Use of a disease-specific interactive patient support tool may be an appreciated , simple , and promising complement to st and ard secondary prevention", "Cardiac rehabilitation ( CR ) is essential for secondary prevention , yet only 10%-30 % of eligible patients attend as geographical proximity is a major barrier . We evaluated a ' virtual ' CR program ( vCRP ) delivered by the Internet to patients in small urban and rural areas . In our study , in- patients ( n=78 ) with acute coronary syndrome or post-revascularization were r and omized to usual care ( UC ) or vCRP . The vCRP was a four-month program that included heart rate monitoring ; physiologic data capture ; education sessions ; ask-an-expert sessions ; and chat sessions with a nurse , exercise specialist and dietitian . Participants were assessed at baseline and four months , and followed for another 12 months . The primary outcome was change in maximal time on the treadmill stress test ( MTT ) between groups adjusted for age , sex , diabetes status and Internet use for health information . The vCRP result ed in a greater increase in MTT by 45.7 seconds ( 95 % CI : 1.0 , 90.5 ) compared to usual care ( p=0.045 ) . Cholesterol levels and dietary quality improved in the vCRP compared to the UC group . Participants perceived the vCRP to be an accessible , convenient and effective way to received healthcare . Eleven ( 30 % ) and 6 ( 18 % ) participants in the UC and vCRP groups , respectively , had cardiovascular-related events ( p=0.275 ) . In conclusion , the vCRP was safe and effective and result ed in sustainable risk reduction without the requirement of face-to-face visits and directly monitored exercise", "Abstract Purpose : To analyse the effect of a six-month home-based phase III cardiac rehabilitation ( CR ) specific exercise program , performed in a virtual reality ( Kinect ) or conventional ( booklet ) environment , on executive function , quality of life and depression , anxiety and stress of subjects with coronary artery disease . Methods : A r and omized controlled trial was conducted with subjects , who had completed phase II , r and omly assigned to intervention group 1 ( IG1 ) , whose program encompassed the use of Kinect ( n = 11 ) ; or intervention group 2 ( IG2 ) , a paper booklet ( n = 11 ) ; or a control group ( CG ) , only subjected to the usual care ( n = 11 ) . The three groups received education on cardiovascular risk factors . The assessed parameters , at baseline ( M0 ) , 3 ( M1 ) and 6 months ( M2 ) , were executive function , control and integration in the implementation of an adequate behaviour in relation to a certain objective , specifically the ability to switch information ( Trail Making Test ) , working memory ( Verbal Digit Span test ) , and selective attention and conflict resolution ability ( Stroop test ) , quality of life ( MacNew question naire ) and depression , anxiety and stress ( Depression , Anxiety and Stress Scale 21 ) . Descriptive and inferential statistical measures were used , significance level was set at .05 . Results : The IG1 revealed significant improvements , in the selective attention and conflict resolution ability , in comparison with the CG in the variable difference M0 − M2 ( p = .021 ) and in comparison with the IG2 in the variable difference M1 − M2 and M0 − M2 ( p = .001 and p = .002 , respectively ) . No significant differences were found in the quality of life , and depression , anxiety and stress . Conclusions : The virtual reality format had improved selective attention and conflict resolution ability , revealing the potential of CR , specifically with virtual reality exercise , on executive function . Implication s for Rehabilitation In cardiac rehabilitation , especially in phase III , it is important to develop and to present alternative strategies , as virtual reality using the Kinect in a home context . Taking into account the relationship between the improvement of the executive function with physical exercise , it is relevant to access the impact of a cardiac rehabilitation program on the executive function . Enhancing the value of the phase III of cardiac rehabilitation", "Background Digital health interventions ( DHI ) have been shown to improve intermediates of cardiovascular health , but their impact on cardiovascular ( CV ) outcomes has not been fully explored . The aim of this study was to determine whether DHI administered during cardiac rehabilitation ( CR ) would reduce CV‐related emergency department ( ED ) visits and rehospitalizations in patients after percutaneous coronary intervention ( PCI ) for acute coronary syndrome ( ACS ) . Methods We r and omized patients undergoing CR following ACS and PCI to st and ard CR ( n = 40 ) or CR + DHI ( n = 40 ) for 3 months with 3 patients withdrawing from CR prior to initiation in the treatment arm and 6 in the control group . The DHI incorporated an online and smartphone‐based CR platform asking the patients to report of dietary and exercise habits throughout CR as well as educational information toward patients ' healthy lifestyles . We obtained data regarding ED visits and rehospitalizations at 180 days , as well as other metrics of secondary CV prevention at baseline and 90 days . Results Baseline demographics were similar between the groups . The DHI + CR group had improved weight loss compared to the control group ( −5.1 ± 6.5 kg vs. −0.8 ± 3.8 kg , respectively , P = .02 ) . Those in the DHI + CR group also showed a non‐significant reduction in CV‐related rehospitalizations plus ED visits compared to the control group at 180 days ( 8.1 % vs 26.6 % ; RR 0.30 , 95 % CI 0.08‐1.10 , P = .054 ) . Conclusions The current study demonstrated that complementary DHI significantly improves weight loss , and might offer a method to reduce CV‐related ED visits plus rehospitalizations in patients after ACS undergoing CR . The study suggests a role for DHI as an adjunct to CR to improve secondary prevention of CV disease . Trial registration This trial is registered at clinical trials.gov ( NCT01883050 )", "OBJECTIVE Pharmacologic treatment for secondary prevention of coronary heart disease ( CHD ) is critical to prevent adverse clinical outcomes . In a r and omized controlled trial , we compared antiplatelet and statin adherence among patients with CHD who received : ( 1 ) text messages ( TM ) for medication reminders and education , ( 2 ) educational TM only , or ( 3 ) No TM . METHODS A mobile health intervention delivered customized TM for 30 days . We assessed and analyzed medication adherence with electronic monitoring devices [ Medication Event Monitoring System ( MEMS ) ] by one-way ANOVA and Welch tests , two-way TM response rates by t-tests , and self-reported adherence ( Morisky Medication Adherence Scale ) by Repeated Measures ANOVA . RESULTS Among 90 patients ( 76 % male , mean age 59.2 years ) , MEMS revealed patients who received TM for antiplatelets had a higher percentage of correct doses taken ( p=0.02 ) , percentage number of doses taken ( p=0.01 ) , and percentage of prescribed doses taken on schedule ( p=0.01 ) . TM response rates were higher for antiplatelets than statins ( p=0.005 ) . Self-reported adherence revealed no significant differences among groups . CONCLUSION TM increased adherence to antiplatelet therapy demonstrated by MEMS and TM responses . PRACTICE IMPLICATION S Feasibility and high satisfaction were established . Mobile health interventions show promise in promoting medication adherence", "PURPOSE Despite demonstrated benefits of cardiac rehabilitation and risk factor reduction , only 11 % to 38 % of eligible patients with cardiovascular disease ( CVD ) participate in cardiac rehabilitation programs . Women and older adults are particularly less likely to participate in cardiac rehabilitation . In an effort to broaden access to cardiac rehabilitation , the authors developed an alternative Internet-based program that allows nurse case managers to provide risk factor management training , risk factor education , and monitoring services to patients with CVD . METHODS The evaluation consisted of a r and omized , clinical trial involving 104 patients with CVD , 53 of whom used the program as a special intervention ( SI ) for 6 months and 51 of whom received usual care ( UC ) . RESULTS The results indicate that fewer cardiovascular events occurred among the SI subjects ( 15.7 % ) than among the UC subjects ( 4.1 % ) ( P = .053 ) , result ing in a gross cost savings of $ 1418 US dollars per patient . With a projected program cost of $ 453 USD per patient , the return on investment is estimated at 213 % . More weight loss occurred in the SI group ( -3.68 pounds ) than in the UC group ( + .47 pounds ) ( P = .003 ) . The differences between the two groups in terms of blood pressure , lipid levels , depression scores , minutes of exercise , and dietary habits were not statistically significant . CONCLUSION An Internet-based case management system could be used as a cost-effective intervention for patients with CVD , either independently or in conjunction with traditional cardiac rehabilitation", "PURPOSE : Efficient ways are needed to implement the secondary prevention ( SP ) of coronary heart disease . Because few studies have investigated Web-based SP programs , our aim was to determine the usefulness of a new Web-based telemonitoring system , connecting patients provided with self-measurement devices and care managers via mobile phone text messages , as a tool for SP . METHODS : A single-blind , r and omized controlled , clinical trial of 203 acute coronary syndrome ( ACS ) survivors , was conducted at a hospital in Madrid , Spain . All patients received lifestyle counseling and usual-care treatment . Patients in the telemonitoring group ( TMG ) sent , through mobile phones , weight , heart rate , and blood pressure ( BP ) weekly , and capillary plasma lipid profile and glucose monthly . A cardiologist accessed these data through a Web interface and sent recommendations via short message service . Main outcome measures were BP , body mass index ( BMI ) , smoking status , low-density lipoprotein-cholesterol ( LDL-c ) , and glycated hemoglobin A1c ( HbA1c ) . RESULTS : At 12-month followup , TMG patients were more likely ( RR = 1.4 ; 95 % CI = 1.1−1.7 ) to experience improvement in cardiovascular risk factors profile than control patients ( 69.6 % vs 50.5 % , P = .010 ) . More TMG patients achieved treatment goals for BP ( 62.1 % vs 42.9 % , P = .012 ) and HbA1c ( 86.4 % vs 54.2 % , P = .018 ) , with no differences in smoking cessation or LDL-c . Body mass index was significantly lower in TMG ( −0.77 kg/m2 vs + 0.29 kg/m2 , P = .005 ) . CONCLUSIONS : A telemonitoring program , via mobile phone messages , appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention , especially for overweight patients", "Objective : Medication adherence is a complex behavior that is influenced by numerous factors . Applying self-efficacy theory , the primary aim of this r and omized controlled trial was to compare medication self-efficacy among patients with coronary heart disease who received : ( a ) text messages ( TMs ) for medication reminders and education , ( b ) TMs for education , or ( c ) no TMs . The second aim was to identify the personal ( sociodemographic and clinical characteristics ) and psychosocial factors that were associated with and predicted medication adherence . Methods : Customized TMs were delivered over 30 days . Repeated measures analysis of variance was used to analyze medication self-efficacy . A multiple regression analysis was performed at baseline and follow-up to determine variables that were associated with and predicted self-reported medication adherence . Results : Among 90 subjects with mean age 59.2 years ( st and ard deviation ( SD ) 9.4 , range 35–83 ) , total scores for medication self-efficacy improved over 30 days ; however , there was no significant difference in this improvement as a function of the different treatment groups ( p=0.64 ) . Controlling for other variables in the model ( age , education , depression , and social support ) , less depression ( p=0.004 ) and higher social support ( p=0.02 ) positively predicted higher medication adherence in the final model . Conclusions : TM medication reminders and /or health education did not improve medication self-efficacy . Further theory testing of current and future models and interventions are required to underst and variables related to self-efficacy and medication adherence . Addressing psychosocial factors such as depression and social support should be a priority to improve medication adherence among patients with coronary heart disease" ]	41182fca-06ff-11f0-808a-c43d1ab1c353
Background / objectives : It is estimated that zinc deficiency affects 17 % of the world 's population , and because of periods of rapid growth children are at an increased risk of deficiency , which may lead to stunting . This paper presents a systematic review and meta- analysis of the r and omised controlled trials ( RCTs ) that assess zinc intake and growth in children aged 1–8 years . This review is part of a larger systematic review by the European Micronutrient Recommendations Aligned Network of Excellence that aims to harmonise the approach to setting micronutrient requirements for optimal health in European population s (www.eurreca.org).Subject/ methods : Search es were performed of literature published up to and including December 2013 using MEDLINE , Embase and the Cochrane Library data bases . Included studies were RCTs in apparently healthy child population s aged from 1 to 8 years that supplied zinc supplements either as capsules or as part of a fortified meal . Pooled meta-analyses were performed when appropriate . Results : Nine studies met the inclusion criteria . We found no significant effect of zinc supplementation of between 2 weeks and 12 months duration on weight gain , height for age , weight for age , length for age , weight for height ( WHZ ) or WHZ scores in children aged 1–8 years . Conclusions : Many of the children in the included studies were already stunted and may have been suffering from multiple micronutrient deficiencies , and therefore zinc supplementation alone may have only a limited effect on growth	[ "BACKGROUND Despite ample food supplies , the incidence of childhood underweight and stunting remains high in Ug and a. Many factors contribute to this situation , but the role of low zinc intakes has not been adequately explored . OBJECTIVE Our objective was to study the effect of zinc supplementation on growth and body composition of preschool children by using the outcome measures of weight , height , and midupper arm circumference ( MUAC ) . DESIGN The study was r and omized , double-blind , placebo-controlled , parallel , and 8 mo long , and incorporated 6 mo of zinc supplementation . Children ( n = 153 ) aged 55.8 + /- 11.2 mo from 3 r and omly selected nursery schools of medium , low , and very low socioeconomic status in a suburb of Kampala took part . The intervention comprised 10 mg Zn ( as ZnSO4 ) or placebo daily in freshly prepared fruit juice , Monday to Friday inclusive . RESULTS Zinc supplementation increased MUAC by the end of the study ( P = 0.029 ) and led to greater weight gain in children from the school of medium socioeconomic status at 3 and 8 mo ( P = 0.019 and P = 0.038 , respectively ) . There was no effect on weight gain of the children from the other schools . Zinc supplementation had no influence on height . Infection rates ( of which 82 % were recorded as malaria ) were lower in the zinc-supplemented group than in control subjects ( P = 0.063 ) . CONCLUSIONS Zinc supplementation may counter the age-related decrease in MUAC often observed in preschool children in developing countries . The study provides evidence that zinc may not be the most limiting nutrient for weight gain in children of poor nutritional status , but may become so as nutritional status improves", "BACKGROUND Several vitamin A supplementation trials have failed to improve the growth rate in children . Addition of zinc to vitamin A might result in enhanced growth . OBJECTIVE This study evaluated the effect on growth in children of simultaneous supplementation with zinc and vitamin A. DESIGN This was a r and omized , double-blind , placebo-controlled intervention trial . Six hundred fifty-three children aged 12 - 35 mo were r and omly assigned to 1 of 4 intervention groups : 20 mg Zn/d for 14 d ( Z group ) , 60000 retinol equivalents ( 200000 IU ) vitamin A on day 14 ( A group ) , zinc plus vitamin A ( ZA group ) , or placebo syrup and placebo capsule ( placebo group ) . Weight and length were measured at enrollment and again after 3 and 6 mo . RESULTS Gains in weight and length during the 6-mo follow-up period were not significantly different among the 4 groups by analysis of variance . Catch-up growth also did not differ significantly among the groups . The proportions of children whose weight-for-age z scores did not change or decreased were 57 % in the Z group , 46 % in the A group , 50 % in the ZA group , and 54 % in the placebo group ( NS ) . The proportions of children whose length-for-age z scores did not change or decreased were 42 % in the Z group , 48 % in the A group , 53 % in the ZA group , and 46 % in the placebo group ( NS ) . CONCLUSION Combined short-term zinc supplementation and a single dose of vitamin A has no significant effects on weight and length increments in children over a 6-mo period", "BACKGROUND Multiple studies have shown the benefits of zinc supplementation among young children in high-risk population s. However , the optimal dose and safe upper level of zinc have not been determined . OBJECTIVES The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration , morbidity , and growth of young children ; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status ; and to determine whether any adverse effects are alleviated by providing copper with zinc . DESIGN This r and omized , double-masked , community-based intervention trial was conducted in 631 Ecuadorian children who were 12 - 30 mo old at baseline and who had initial length-for-age z scores Children received 1 of 5 daily supplements for 6 mo : 3 , 7 , or 10 mg Zn as zinc sulfate , 10 mg Zn + 0.5 mg Cu as copper sulfate , or placebo . RESULTS The change in plasma zinc concentration from baseline was positively related to the zinc dose ( P Zinc supplementation , including doses as low as 3 mg/d , reduced the incidence of diarrhea by 21 - 42 % ( P CONCLUSIONS Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population . There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status . The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children", "BACKGROUND Zinc supplements are used extensively in medicine and research and for public health purpose s in the prevention and treatment of zinc deficiency . However , little is known about the efficiency of zinc utilization after different doses . OBJECTIVE The objective was to determine the relation between dose of aqueous zinc and absorbed zinc ( AZ ) in healthy adults . DESIGN Eight healthy adults ( 3 men and 5 women ) aged 33.8 + /- 9.8 y ( x + /- SD ) received 3 pairs of zinc doses ( 2 and 5 , 10 and 15 , and 20 and 30 mg ) in r and om order in 3 phases ( 1 pair per phase ) . There was a 3-wk washout between phases . Aqueous zinc sulfate labeled with 70Zn or 68Zn was orally administered in the postabsorptive state on days 1 and 6 , respectively ; intravenous 67Zn was administered 1 h after the first oral zinc dose . Two urine sample s were collected daily from days 3 to 15 ; zinc isotopic ratios were determined by inductively coupled plasma mass spectrometry . Fractional absorption of zinc ( FAZ ) was determined by dual-isotope-tracer ratio ; AZ was calculated by multiplying FAZ by dose . RESULTS Mean ( + /-SD ) AZ values at doses of 2.2 , 5.2 , 10.4 , 15.2 , 20.3 , and 30.1 mg ingested Zn were 1.6 + /- 0.4 , 3.5 + /- 1.3 , 7.4 + /- 1.0 , 9.5 + /- 2.2 , 11.0 + /- 4.4 , and 11.2 + /- 2.1 mg , respectively . A saturable dose-response model , the Hill equation , was selected to model the relation of AZ to ingested zinc . Parameter estimation by nonlinear regression predicted a maximum zinc absorption of 13 mg for larger doses . CONCLUSIONS Increases in aqueous zinc doses > 20 mg result in relatively small and progressively diminishing increases in AZ postabsorptively in healthy adults", "The effects of a zinc supplement on growth velocity were assessed in a double-blind , pair-matched controlled study in 40 children with low growth percentiles . Participants were low-income Spanish-American children , 2 to 6 yr of age with heights below the 10th percentile and nutritional or biochemical evidence of zinc deficiency . After 1 yr , the mean height velocity of the zinc-supplemented children was slightly , but significantly ( p less than 0.005 ) , greater than that of control children . This effect was primarily due to a greater height achievement of the zinc-supplemented boys . Increases in height-for-age z-scores were also significant for the supplemented males ( p less than 0.001 ) and for the combined sexes ( p less than 0.05 ) . This study indicates the existence of a growth-limiting syndrome of mild zinc deficiency in children", "Changes in growth , body composition , and zinc indexes were evaluated after 25 wk in a double-blind zinc-supplementation study of 162 periurban Guatemalan children aged 81.5 + /- 7.0 mo ( mean + /- SD ) . Children receiving the zinc supplement ( 10 mg Zn/d as amino acid chelate ) for 90.1 + /- 9.2 d had higher mean fasting plasma zinc ( 16.2 + /- 2.9 vs 14.9 + /- 2.1 mumol/L , P median triceps skinfold Z score ( 0.50 vs 0.38 , P median midarm circumference ( MAC ) Z score ( -0.03 vs -0.20 , P hair zinc classified as 1.68 mumol/g was the only laboratory variable that explained some of the variance in final Z scores of midarm-muscle area ( P MAC ( P zinc supplement with changes in indexes of body composition rather than growth", "Physical growth disorders in under 5-year-old children are a common health problem in many countries including Iran . The aim of this study was to determine effects of supplemental zinc on physical growth in preschool children with retarded linear growth . This study was a community-based r and omized controlled trial on 2–5-year-old children with height-for-age below 25th percentile of National Center for Health Statistics growth chart . Ninety children were r and omly assigned in zinc group ( ZG ) or placebo group ( PG ) . After 6 months of zinc or placebo supplementation , we followed up the children for another 6 months . Anthropometric indicators were measured before the intervention and then monthly for 11 months . Forty children in ZG and 45 in PG concluded the study . Zinc supplementation increased weight gain in boys ( P = 0.04 ) and girls ( P = 0.05 ) compared to placebo but had no significant effect on mid-upper arm circumference increment in either sexes . The most significant ( P = 0.001 ) effect of Zinc supplementation was seen in boys ’ height increment at the end of follow-up period . Stunted growth rate in ZG changed significantly ( P = 0.01 ) from 26.7 % to 2.5 % throughout the study . This study showed that daily supplementation of 5 mg elemental zinc for 6 months improves physical growth in terms of height increment and weight gain in children with undesirable linear growth , especially in boys", "In rural Mexico and in many developing countries micronutrient deficiencies , growth stunting , and morbidity from infectious diseases are highly prevalent in young children . We assessed the extent to which growth stunting could be reversed and the number of infectious disease episodes reduced by zinc and /or iron supplementation . In a double-blind , r and omized community trial 219 Mexican preschoolers were supplemented with either 20 mg Zn as zinc methionine , 20 mg Fe as ferrous sulfate , 20 mg Zn + 20 mg Fe , or a placebo . After 12 mo , plasma zinc increased significantly in the two zinc-treated groups , and plasma ferritin was significantly higher in the two iron-treated groups . There was no effect of treatments on growth velocity or body composition . Children in both zinc-supplemented groups had fewer episodes of disease ( zinc alone , 3.9 + /- 0.3 ; zinc+iron , 3.7 + /- 0.4 ; placebo , 4.6 + /- 0.5 ; P diarrhea ( zinc alone , 0.7 + /- 0.1 ; zinc+iron , 0.8 + /- 0.1 ; placebo , 1.1 + /- 0.2 ; P Zinc and zinc+iron supplements reduced morbidity but had no effect on growth or body composition", "OBJECTIVE To assess the impact of zinc supplementation on nutritional and biochemical parameters among children aged 12 to 59 months . METHODS A blinded r and omized clinical trial was carried out with 58 children aged 12 to 59 months included in the Programa Governamental de Combate a Carências Nutricionais ( National Child Nutritional Program ) , which provided them with 2 kg of iron-fortified milk . The supplementation group ( n = 28 ) received 10 mg/day of zinc sulfate for four months , and the control group ( n = 30 ) received placebo . The following parameters were used to assess the nutritional status : weight-for-height and height-for-age expressed as z scores , according to National Center for Health Statistics ( NCHS ) st and ards , biochemical measurements of serum iron and serum zinc , and hemoglobin and hematocrit levels . RESULTS Zinc supplementation did not have a remarkable influence on anthropometric parameters . Baseline serum zinc levels were low in both groups . After supplementation , variations in mean hemoglobin ( p = 0.002 ) , hematocrit ( p = 0.001 ) , serum zinc ( p = 0.023 ) , and serum iron ( p = 0.013 ) levels significantly increased in the zinc supplementation group . CONCLUSION Zinc supplementation improved hemoglobin response and normalized serum zinc concentration . The results show the importance of establishing policies for nutritional care that can tackle zinc deficiency as well", "OBJECTIVE To assess the effect of zinc supplementation on respiratory tract disease , immunity and growth in malnourished children . DESIGN A r and omized double-blind placebo-controlled trial . SETTING A day-care center in Quito , Ecuador . SUBJECTS Fifty children ( 12 - 59 months old ) recruited by height-for-age and weight-for-age deficit . INTERVENTIONS Twenty-five children ( supplemented , S group ) received 10 mg/day of zinc as zinc sulfate , and 25 ( nonsupplemented , NS group ) received a placebo during 60 days . All were also observed during a 60-day postsupplementation period . Two children of the S group dropped out . Daily the clinical presence of cough , respiratory tract secretions , and fever , was recorded . On days 0,60 and 120 , the cutaneous delayed-type hypersensitivity ( DTH ) to multiple antigens , and anthropometric parameters were assessed . On days 0 and 60 serum zinc levels were also measured . RESULTS On day 60 , DTH was significantly larger ( 20.8 + /- 7.1 vs 16.1 + /- 9.7 mm ) , and serum zinc levels were significantly higher ( 118.6 + /- 47.1 vs 83.1 + /- 24.5 micrograms/dl ) in the S group than in the NS group ( P incidence of fever [ relative risk ( RR ) : 0.30 , c.i . = 0.08- 0.95 , P = 0.02 ] , cough ( RR ) : 0.52 , c.i . = 0.32 - 0.84 , P = 0.004 ) and upper respiratory tract secretions (RR):0.72 , c.i . = 0.59 - 0.88 , P = 0.001 ) was lower in the S group than in the NS group at day 60 . At the end of the postsupplementation observation period ( day 120 ) , the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups . The incidence of cough was higher at day 120 in the S group than in the NS group ( RR ) : 2.28 , c.i . = 1.37 - 3.83 , P = 0.001 ) . CONCLUSIONS This study supports a role for zinc in immunity , and immunity to respiratory infections , while pointing out the need for larger studies", "A double-blind , pair-matched 12-mo study examined the effects of a zinc supplement ( 10 mg Zn/d as ZnSO4 ) on linear growth , taste acuity , attention span , biochemical indices , and energy intakes of 60 boys ( aged 5 - 7 y ) with height less than or equal to 15th and midparent height greater than 25th percentiles . Boys with initial hair Zn less than 1.68 mumol/g ( n = 16 ) had a lower mean ( + /- SD ) weight-for-age Z score ( -0.44 + /- 0.59 vs -0.08 + /- 0.84 ) , and a higher median recognition threshold for salt ( 15 vs 7.5 mmol ; p = 0.02 ) than those with hair Zn greater than 1.68 mumol/g . Only boys with hair Zn less than 1.68 mumol/g responded to the Zn supplement with a higher mean change in height-for-age Z score ( p less than 0.05 ) ; taste acuity , energy intakes , and attention span were unaffected . A growth-limiting Zn deficiency syndrome exists in boys with low height percentiles , hair Zn levels less than 1.68 mumol/g , and impaired taste acuity" ]	41183042-06ff-11f0-808a-c43d1ab1c353
Electroacupuncture ( EA ) is considered to be a promising alternative therapy to relieve the menstrual pain for primary dysmenorrhea ( PD ) , but the conclusion is controversial . Here , we conducted a systematic review and meta- analysis specifically to evaluate the clinical efficacy from r and omized controlled trials ( RCTs ) on the use of EA in patients with PD . PubMed , Embase , ISI Web of Science , CENTRAL , CNKI , and Wanfang were search ed to identify RCTs that evaluated the effectiveness of EA for PD . The outcome measurements included visual analogue scale ( VAS ) , verbal rating scale ( VRS ) , COX retrospective symptom scale ( RSS ) , and the curative rate . Nine RCTs with high risk of bias were included for meta- analysis . The combined VAS 30 minutes after the completion of intervention favoured EA at SP6 when compared with EA at GB39 , nonacupoints , and waiting-list groups . EA was superior to pharmacological treatment when the treatment duration lasted for three menstrual cycles , evidence d by significantly higher curative rate . No statistically significant differences between EA at SP6 and control groups were found regarding the VRS , RSS-COX1 , and RSS-COX2 . The findings of our study suggested that EA can provide considerable immediate analgesia effect for PD . Additional studies with rigorous design and larger sample sizes are needed	[ "OBJECTIVE The objective of this study was to compare immediate effect of acupuncture at SP6 on uterine arterial blood flow in primary dysmenorrhea with that of GB39 . DESIGN This was a prospect i ve , r and omized clinical trial . SETTING Sixty-six ( 66 ) patients with primary dysmenorrhea from the Affiliated Hospital of Shangdong University of Traditional Chinese Medicine were recruited . INTERVENTIONS The SP6 group ( n = 32 ) was treated with manual acupuncture at bilateral SP6 for 5 minutes after obtaining needling sensation ( de qi ) during the period of menstrual pain , whereas the control group ( n = 34 ) was needled at GB39 of both sides for 5 minutes when they suffered menstrual pain . MAIN OUTCOME MEASURES Differences in pulsatility index ( PI ) , resistance index ( RI ) , and ratio of systolic peak and diastolic peak ( A/B ) in uterine arteries were the main outcome measures . RESULTS Highly significant reductions were observed in the SP6 treatment group 5 minutes after treatment in menstrual pain scores ( 8.17 ± 1.90 versus 11.20 ± 2.66 ; p values of PI ( 1.75 ± 0.48 versus 2.32 ± 0.70 ; p changes of menstrual pain scores ( 3.03 ± 2.36 versus 0.00 ± 0.29 ; p values of PI ( 0.57 ± 0.42 versus -0.10 ± 0.58 ; p changes in menstrual pain scores , values of PI , RI , or A/B before and after treatment in the GB39 control group ( p > 0.05 ) . No adverse events from treatment were reported . CONCLUSIONS This study suggests that needling at SP6 can immediately improve uterine arterial blood flow of patients with primary dysmenorrhea , while GB39 does not have these effects", "Background Though moxibustion is frequently used to treat primary dysmenorrhea in China , relevant evidence supporting its effectiveness is still scanty . Methods This study was a pragmatic r and omized , conventional drug controlled , open-labeled clinical trial . After initial screen , 152 eligible participants were averagely r and omized to receive two different treatment strategies : Moxibustion and conventional drugs . Participants and practitioners were not blinded in this study . The duration of each treatment was 3 months . The primary outcome was pain relief measured by the Visual Analogue Scale . The menstrual pain severity was recorded in a menstrual pain diary . Results 152 eligible patients were included but only 133 of them eventually completed the whole treatment course . The results showed that the menstrual pain intensity in experimental group and control group was reduced from 6.38±1.28 and 6.41±1.29 , respectively , at baseline , to 2.54±1.41 and 2.47±1.29 after treatment . The pain reduction was not significantly different between these two groups ( P = 0.76 ) , however ; the pain intensity was significantly reduced relative to baseline for each group ( P the effectiveness of moxibustion sustained and started to be superior to the drug ’s effect ( -0.87 , 95%CI -1.32 to -0.42 , P ) . Secondary outcome analyses showed that moxibustion was as effective as drugs in alleviating menstrual pain-related symptoms . The serum levels of pain mediators , such as PGF2α , OT , vWF , β-EP , PGE2 , were significantly improved after treatment in both groups ( P events were reported in this trial . Conclusions Both moxibustion and conventional drug showed desirable merits in managing menstrual pain , given their treatment effects and economic costs . This study as a pragmatic trial only demonstrates the effectiveness , not the efficacy , of moxibustion for menstrual pain . It ca n’t rule out the effect of psychological factors during treatment process , because no blind procedure or sham control was used due to availability . In clinical practice , moxibustion should be used at the discretion of patients and their physicians . Trial registration ClinialTrials.gov", "Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose", "Importance Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome , without supporting clinical evidence . Objective To assess whether active acupuncture , either alone or combined with clomiphene , increases the likelihood of live births among women with polycystic ovary syndrome . Design , Setting , and Participants A double-blind ( clomiphene vs placebo ) , single-blind ( active vs control acupuncture ) factorial trial was conducted at 21 sites ( 27 hospitals ) in mainl and China between July 6 , 2012 , and November 18 , 2014 , with 10 months of pregnancy follow-up until October 7 , 2015 . Chinese women with polycystic ovary syndrome were r and omized in a 1:1:1:1 ratio to 4 groups . Interventions Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle , for up to 4 cycles . The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation ; the control acupuncture group received superficial needle insertion , no manual stimulation , and mock electricity . Main Outcomes and Measures The primary outcome was live birth . Secondary outcomes included adverse events . Results Among the 1000 r and omized women ( mean [ SD ] age , 27.9 [ 3.3 ] years ; mean [ SD ] body mass index , 24.2 [ 4.3 ] ) , 250 were r and omized to each group ; a total of 926 women ( 92.6 % ) completed the trial . Live births occurred in 69 of 235 women ( 29.4 % ) in the active acupuncture plus clomiphene group , 66 of 236 ( 28.0 % ) in the control acupuncture plus clomiphene group , 31 of 223 ( 13.9 % ) in the active acupuncture plus placebo group , and 39 of 232 ( 16.8 % ) in the control acupuncture plus placebo group . There was no significant interaction between active acupuncture and clomiphene ( P = .39 ) , so main effects were evaluated . The live birth rate was significantly higher in the women treated with clomiphene than with placebo ( 135 of 471 [ 28.7 % ] vs 70 of 455 [ 15.4 % ] , respectively ; difference , 13.3 % ; 95 % CI , 8.0 % to 18.5 % ) and not significantly different between women treated with active vs control acupuncture ( 100 of 458 [ 21.8 % ] vs 105 of 468 [ 22.4 % ] , respectively ; difference , −0.6 % ; 95 % CI , −5.9 % to 4.7 % ) . Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture ( diarrhea : 25 of 500 [ 5.0 % ] vs 8 of 500 [ 1.6 % ] , respectively ; difference , 3.4 % ; 95 % CI , 1.2 % to 5.6 % ; bruising : 37 of 500 [ 7.4 % ] vs 9 of 500 [ 1.8 % ] , respectively ; difference , 5.6 % ; 95 % CI , 3.0 % to 8.2 % ) . Conclusions and Relevance Among Chinese women with polycystic ovary syndrome , the use of acupuncture with or without clomiphene , compared with control acupuncture and placebo , did not increase live births . This finding does not support acupuncture as an infertility treatment in such women . Trial Registration clinical trials.gov Identifier :", "OBJECTIVE To observe the clinical therapeutic effects of acupuncture at single point Shiqizhui ( EX-B8 ) and multi-points in time-varying treatment for primary dysmenorrhea . METHODS 600 patients with primary dysmenorrhea were r and omly assigned to the single point group ( n=200 ) including group A ( treating before the menstruation , n=100 ) and group B ( immediately treating as soon as pain occurrence , n=100 ) , the multi-points group ( n=200 ) including group C ( treating before the menstruation , n=100 ) and group D ( immediately treating as soon as pain occurrence , n=100 ) , or the control group , group E ( n=200 , no treatment ) . The therapeutic effects were analyzed after treatment for three menstrual cycles and interviewed for three follow-up periods . RESULTS Acupuncture could effectively relieve menstrual pain for primary dysmenorrhea compared with the control group ( P Immediate pain relief occurred following acupuncture within 5 min in group B ( P menstrual pain for VAS scores . Both group A and group C obviously relieved menstrual pain ( P CMSS scores in cycle 1 . CONCLUSION Treating before the menstruation is better than immediately treating as soon as pain occurrence at the improvement in symptoms of dysmenorrheal at multi-points . And single point is better than multi-points when immediately treating as soon as pain occurrence . The present trial suggest Shiqizhui ( EX-B8 ) should be chosen as a convenient point", "BACKGROUND Acupuncture is often used for primary dysmenorrhea . But there is no convincing evidence due to low method ological quality . We aim to assess immediate effect of acupuncture at specific acupoint compared with unrelated acupoint and nonacupoint on primary dysmenorrhea . METHODS The Acupuncture Analgesia Effect in Primary Dysmenorrhoea-II is a multicenter controlled trial conducted in six large hospitals of China . Patients who met inclusion criteria were r and omly assigned to classic acupoint ( N = 167 ) , unrelated acupoint ( N = 167 ) , or non-acupoint ( N = 167 ) group on a 1:1:1 basis . They received three sessions with electro-acupuncture at a classic acupoint ( Sanyinjiao , SP6 ) , or an unrelated acupoint ( Xuanzhong , GB39 ) , or nonacupoint location , respectively . The primary outcome was subjective pain as measured by a 100-mm visual analog scale ( VAS ) . Measurements were obtained at 0 , 5 , 10 , 30 , and 60 minutes following the first intervention . In addition , patients scored changes of general complaints using Cox retrospective symptom scales ( RSS-Cox ) and 7-point verbal rating scale ( VRS ) during three menstrual cycles . Secondary outcomes included VAS score for average pain , pain total time , additional in-bed time , and proportion of participants using analgesics during three menstrual cycles . FINDINGS Five hundred and one people underwent r and om assignment . The primary comparison of VAS scores following the first intervention demonstrated that classic acupoint group was more effective both than unrelated acupoint ( -4.0 mm , 95 % CI -7.1 to -0.9 , P = 0.010 ) and nonacupoint ( -4.0 mm , 95 % CI -7.0 to -0.9 , P = 0.012 ) groups . However , no significant differences were detected among the three acupuncture groups for RSS-Cox or VRS outcomes . The per- protocol analysis showed similar pattern . No serious adverse events were noted . CONCLUSION Specific acupoint acupuncture produced a statistically , but not clinical ly , significant effect compared with unrelated acupoint and nonacupoint acupuncture in primary dysmenorrhea patients . Future studies should focus on effects of multiple points acupuncture on primary dysmenorrhea", "This open-label r and omized controlled trial was design ed to compare the efficacy of acupuncture and combined oral contraceptive ( COC ) pill in treating moderate-to-severe primary dysmenorrhea . Fifty-two participants were r and omly assigned to receive either acupuncture ( n = 27 ) or COC ( n = 25 ) for three menstrual cycles . Mefenamic acid was prescribed as a recue analgesic drug with both groups . The statistical approach used for efficacy and safety assessment s was intention-to-treat analysis . By the end of the study , both treatments had result ed in significant improvement over baselines in all outcomes , that is , maximal dysmenorrhea pain scores , days suffering from dysmenorrhea , amount of rescue analgesic used , and quality of life assessed by SF-36 question naire . Over the three treatment cycles , COC caused greater reduction in maximal pain scores than acupuncture , while improvements in the remaining outcomes were comparable . Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33 % below their baseline . Response rates following both interventions at the end of the study were not statistically different . Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC . In conclusion , acupuncture is an alternative option for relieving dysmenorrhea , especially when COC is not a favorable choice", "Background Deqi is a central concept in traditional Chinese acupuncture . We performed a secondary analysis on data from a larger r and omized controlled trial ( RCT ) in order to assess the effect of acupuncture on deqi traits and pain intensity in primary dysmenorrhea . Methods A total of 60 primary dysmenorrhea patients were enrolled and r and omly assigned to one of three treatment groups . Acupuncture was given at SP6 , GB39 or nonacupoint . Subjective pain was measured by a 100-mm visual analogue scale ( VAS ) before and after acupuncture . The Massachusetts General Hospital acupuncture sensation scales ( MASS ) with minor modification was used to rate deqi sensations during acupuncture . Results The results showed that VAS scores of pain after acupuncture were significantly decreased comparing to before acupuncture treatment in all three groups ( P = 0.000 ) . However , no significant differences were found among three groups at the beginning or end of acupuncture treatment ( P = 0.928 , P = 0.419 ) . Conclusions There was no statistical difference among three groups in terms of intensity of deqi feeling . The types of sensation were similar across the groups with only minor differences among them . Trial registration Trial registration number : Controlled-Trials.com IS RCT N24863192", "OBJECTIVE To evaluate the analgesic and therapeutic effects of electro-superficial-acupuncture ( ESA ) of Sanyinjiao ( SP6 ) for treating primary dysmenorrhea ( PD ) . METHODS A total of 171 patients were r and omly divided into ESA ( n=57 ) , superficial acupuncture ( SA ) ( n=57 ) and medication ( n=57 ) groups . For patients in SA group , bilateral SP6 were punctured superficially with special single-use needles , and for those in ESA group , after puncturing , electric stimulation ( 60 Hz , 2 - 3 V ) was applied to SP6 for 30 min . Patients of medication group were ordered to take Brufen sustained-release capsules ( 0.3 mg , b. i. d. , for 3 days ) , then , take it again from the 3rd day on before the onset of menstruation to the 2nd day after the onset . The cumulative score of clinical symptoms were evaluated before and after the treatment . RESULTS Comparison among 3 groups showed that the difference values of score ( pre-treatment -- post-treatment ) of both ESA and SA groups were significantly bigger than that of medication group ( P complete relief of dysmenorrhea of ESA group were significantly more than those of SA group during the 1st menstrual cycle ( P cured cases were 40 , 38 and 10 , the markedly effective were 9 , 10 and 27 , the effective were 5 , 4 and 7 , and the failed were 3 , 5 and 13 , with the total effective rates being 94.74 % , 91.23 % and 77.19 % respectively . The effective rates of ESA and SA groups were significantly higher than that of medication group ( P analgesic effect of both ESA and SA at SP6 for PD patients is significantly better than that of oral administration of Brufen", "OBJECTIVE The objective of this study was to compare the effects of Sanyinjiao ( SP6 ) , Xuanzhong ( GB39 ) , and an adjacent non-meridian point on menstrual pain and uterine arterial blood flow in primary dysmenorrhea patients . DESIGN The design of the study was a prospect i ve , r and omized controlled trial . SETTING The setting of the study was the Sh and ong Institute of Medical Imaging , Jinan , China . PATIENTS The patients were 52 women with primary dysmenorrhea . INTERVENTIONS Women received electroacupuncture ( EA ) at SP6 ( n=13 ) , GB39 ( n=14 ) , and an adjacent non-meridian point ( n=12 ) , respectively , for 10 minutes when scored ≥40 on a 100-mm visual analog scale ( VAS ) , and for 30 minutes on the next 2 days . There was no EA in the waiting list group ( n=13 ) . OUTCOME MEASURES Primary outcomes were menstrual pain , resistance index ( RI ) , and the ratio between peak systolic to end-diastolic flow velocity ( S/D ) in uterine arteries . Secondary outcomes included verbal rating scale ( VRS ) and retrospective symptom scale ( RSS ) . RESULTS The SP6 group had a highly significant reduction in VAS scores compared with the waiting list group ( -23.19 mm , 95 % confidence interval [CI]-32.06 to -14.33 , P reduction in VRS scores was found in the SP6 group compared with the GB39 group ( P=0.034 ) and the non-meridian point group ( P=0.038 ) . There were no significant differences of RI , S/D-values and RSS scores among the four groups ( P>0.05 ) . CONCLUSIONS EA at SP6 can immediately relieve menstrual pain and minimize the influence of pain on daily life compared with GB39 and an adjacent non-meridian point . The data preliminarily show the specificity of SP6 for the immediate pain relief of primary dysmenorrhea", "BACKGROUND Acupuncture is often used for primary dysmenorrhea . OBJECTIVE To assess the efficacy of a single point of acupuncture in the management of primary dysmenorrhea compared with sham acupuncture and no acupuncture . METHODOLOGY Patients with primary dysmenorrhea were r and omly assigned to acupoint group ( n=50 ) , unrelated acupoint group ( n=50 ) , nonacupoint group ( n=46 ) , or no acupuncture group ( n=48 ) . Acupuncture and sham acupuncture were administered once-daily for 3 days with electro-acupuncture at Sanyinjiao ( SP6 ) that was specifically design ed to treat primary dysmenorrhea , or an unrelated acupoint ( Xuanzhong , GB39 ) , or nonacupoint location . The primary outcome was pain intensity as measured by a 100-mm visual analog scale ( VAS ) at baseline ; 5 , 10 , 30 , and 60 minutes following the start of the first intervention . Cox retrospective symptom scale ( RSS ) , verbal rating scale ( VRS ) , pain total time , and proportion of participants using analgesics were also recorded during three menstrual cycles . RESULTS The primary comparison of VAS scores demonstrated that patients receiving acupuncture ( -15.56 mm , 95 % CI -22.16 to -8.95 , P no acupuncture group . There were no significant differences among the four groups with respect to secondary outcomes . CONCLUSION Acupuncture was better than no acupuncture for relieving the pain of dysmenorrhea following a single point of acupuncture , but no differences were detected between acupoint acupuncture and unrelated acupoint acupuncture , acupoint acupuncture and nonacupoint acupuncture", "OBJECTIVE To compare the cumulative analgesic effect of electroacupuncture ( EA ) stimulation of Sanyinjiao ( SP 6 ) , Xuanzhong ( GB 39 ) and non-acupoint for primary dysmenorrhea patients . METHODS A total of 200 patients with primary dysmenorrhea were r and omly assigned to Sanyinjiao ( SP 6 , a dysmenorrheal-relieving related acupoint ) group , Xuanzhong ( GB 39 , an unrelated acupoint ) group , non-acupoint group and control group , with 50 cases in each group . The participants were administered with EA ( 2 Hz/100 Hz , 0.5 - 1.6 mA ) at SP 6 , GB 39 and non-acupoint for 30 min , once daily for 3 consecutive days . The intensity of the pain was ranked from 0 ( no pain ) to 100 ( intolerable ) using visual analogue scale ( VAS ) and RSS ( Cox retrospective symptom scale ) severity rating scores ( RSS-COX 2 ) before and after three interventions . RESULTS In comparison with the control group , VAS and RSS-COX 2 scores were significantly lower in the SP 36 , GB 39 and non-acupoint groups ( P VAS and RSS-COX 2 scores ( P > 0.05 ) . CONCLUSION EA stimulation of SP 6 , GB 39 and non-acupoint has a good cumulative analgesic effect in patients with primary dysmenorrhea", "OBJECTIVE To compare the effects of instant electroacupuncture ( EA ) at the different acupoints on IP3 in the uterus tissue of dysmenorrhea model rats so as to investigate the specificity of acupoints . METHODS Fifty female SD rats were r and omly divided into a saline group , a model group , a Sanyinjiao ( SF 6 ) group , a Xuehai ( SP 10 ) group and a Hegu ( LI 4 ) group , 10 rats in each group . The rats were given subcutaneous injection of Estradiol Beozoate injection for 10 consecutive days except those in the saline group , and intraperitoneal injection of 2U Oxytocin at 1 h after the last administration to create the dysmenorrhea rats model , and the saline group was given the same dose of saline every day . On the 10th day the rats in each EA group were given EA 20 min , and the rats in the saline group and model group were bound 20 min , and the writhing response was observed at the same time . The uterine IP3 contents were detected with enzyme-linked immunosorbent assay method . RESULTS ( 1 ) Compared with ( 0.311+/- 0.253 ) in the saline group , the writhing scores per minute of ( 5.867 + /- 3.442 ) in the model group and ( 2.311 + /- 0.957 ) in the Xuehai ( SP 10 ) group were both increased significantly ( P ( SP 6 ) group and ( 0.743 + /- 0.306 ) in the Hegu ( LI 4 ) group showed no significant differences ( P > 0.05 ) . Compared with that in the model group , the writhing scores per minute decreased significantly ( all P 0.05 ) . ( 2 ) Compared with ( 2.698 + /- 1.491 ) ng/mg in the saline group , IP3 contents of the uterus of ( 0.813 + /- 0.899 ) ng/mg in the model group , ( 1.740 + /- 0.375 ) ng/mg in the Sanyinjiao ( SP 6 ) group and ( 0.692 + /- 0.212 ) ng/mg in the Hegu ( LI 4 ) group were all lower significantly ( P Xuehai ( SP 10 ) group showed no significant differences ( P > 0.05 ) . Compared with that in the model group , IP3 content of the uterus in the Hegu ( LI 4 ) group showed no significant difference ( P > 0.05 ) , and those in the Sanyinjiao ( SP 6 ) group and in the Xuehai ( SP 10 ) group increased significantly ( both P Hegu ( II 4 ) group ( P dysmenorrhea symptoms , but there is obvious specificity of acupoint effects in the regulation of IP3 . Electroacupuncture at \" Sanyinjiao ( SP 6 ) \" Xuehai ( SP 10 ) \" has more marked effect in dysmenorrhea model rats", "Objective To explore the physiologic mechanism of immediate analgesic effect of acupuncture in primary dysmenorrhea patients . Methods Forty primary dysmenorrhea patients were r and omized into the Sanyinjiao ( SP6 ) acupuncture group , Xuanzhong ( GB39 ) control group , nonacupoint control group , or no acupuncture group . Patients in the 3 acupuncture groups were treated with electroacupuncture at assigned points lasting 30 minutes , whereas patients in no acupuncture group did not receive any acupuncture intervention . Before and after acupuncture , visual analogue scale ( VAS ) scores were recorded and blood sample s were taken for the measurement of the plasma levels of 4 principal prostagl and ins ( PGE2 , PGF2a , TXB2 , and 6-keto PGF1a ) . Results The VAS scores for pain intensity significant decreased in patients who received acupuncture compared with those had no acupuncture intervention . However , there were no significant differences among patients in the 3 acupuncture groups after acupuncture . In addition , no statistically significant differences were observed in the plasma PGE2 , PGF2a , TXB2 , or 6-keto PGF1a levels and the ratios of PGF2a/PGE2 , and TXB2/6-keto PGF1a after acupuncture at SP6 . Conclusions The immediate analgesic effect of SP6 might not be mediated by changes in the prostagl and in levels" ]	411830ba-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Prebiotics ( commonly oligosaccharides ) added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens . OBJECTIVES To determine the effect of prebiotic given to infants for the prevention of allergy . SEARCH METHODS We performed an up date d search in August 2012 of the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( The Cochrane Library 2012 , Issue 8) , MEDLINE , EMBASE , conference proceedings , citations , expert informants and clinical trials registries . SELECTION CRITERIA R and omised and quasi-r and omised controlled trials that compared the use of a prebiotic to no prebiotic , or a specific prebiotic compared to a different prebiotic in infants for prevention of allergy . DATA COLLECTION AND ANALYSIS Assessment of trial quality , data extraction and synthesis of data were performed using the st and ard methods of The Cochrane Collaboration . MAIN RESULTS The 2012 up date identified 13 studies classified as ongoing or awaiting classification ( yet to report allergy outcomes ) . Forty-three studies were excluded , primarily as no allergy data were reported , although none of these enrolled infants were at high risk of allergy . Four studies enrolling 1428 infants were eligible for inclusion . All studies were at high risk of attrition bias . Allergy outcomes were reported from four months to two years of age . Meta- analysis of two studies ( 226 infants ) found no significant difference in infant asthma although significant heterogeneity was found between studies . Meta- analysis of four studies found a significant reduction in eczema ( 1218 infants , typical risk ratio 0.68 , 95 % CI 0.48 to 0.97 ; typical risk difference -0.04 , 95 % CI -0.07 to -0.00 ; number needed to treat to benefit ( NNTB ) 25 , 95 % CI 14 to > 100 ; P = 0.03 ) . No statistically significant heterogeneity was found between studies . One study reported no significant difference in urticaria . No statistically significant subgroup differences were found according to infant risk of allergy or type of infant feed . However , individual studies reported a significant reduction in asthma and eczema from supplementation with a mixture of galacto- and fructo-oligosaccharide ( GOS/FOS 9:1 ratio ) ( 8 g/L ) in infants at high risk of allergy ; and in eczema from supplementation with GOS/FOS ( 9:1 ) ( 6.8 g/L ) and acidic oligosacccharide ( 1.2 g/L ) in infants not selected for allergy risk . AUTHORS ' CONCLUSIONS Further research is needed before routine use of prebiotics can be recommended for prevention of allergy in formula fed infants . There is some evidence that a prebiotic supplement added to infant feeds may prevent eczema . It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk population s ; or whether it may have an effect on other allergic diseases including asthma	[ "Development of new infant formulas aims to replicate the benefits of breast milk . One benefit of breast milk over infant formulas is greater gastrointestinal comfort . We compared indicators of gastrointestinal comfort in infants fed a whey-predominant formula containing long-chain polyunsaturated fatty acids , galacto-oligo-saccharides and fructo-oligosaccharides , and infants fed a control casein-predominant formula without additional ingredients . The single-centre , prospect i ve , double-blind , controlled trial r and omly assigned healthy , full-term infants ( n=144 ) to receive exclusively either experimental or control formula from 30 days to 4 months of age . A group of exclusively breast-fed infants served as reference ( n=80 ) . At 1 , 2 , 3 , and 4 months , infants ' growth parameters were measured and their health assessed . Parents recorded frequency and physical characteristics of infants ' stool , frequency of regurgitation , vomiting , crying and colic . At 2-months , gastric emptying ( ultrasound ) and intestinal transit time ( H2 breath test ) were measured , and stool sample s collected for bacterial analysis . Compared to the control ( n=69 ) , fewer of the experimental group ( n=67 ) had hard stools ( 0.7 vs 7.5 % , p soft stools ( 90.8 vs 82.3 % , p stool microbiota composition ( mean % bifidobacteria : 78.1 ( experimental , n=17 ) , 63.7 ( control , n=16 ) , 74.3 ( breast-fed , n=20 ) , gastric transit times ( 59.6 ( experimental , n=53 ) , 61.4 ( control , n=62 ) , 55.9 ( breast-fed , n=67 ) minutes ) and intestinal transit times ( data not shown ) were closer to that of the breast-fed group . Growth parameter values were similar for all groups . The data suggest that , in infants , the prebiotic-containing whey-based formula provides superior gastrointestinal comfort than a control formula", "The gastrointestinal inflammatory response may play a role in the susceptibility of preterm infants for infections . We previously reported a trend toward lower endogenous infection morbidity after enteral supplementation of neutral and acidic oligosaccharides ( SCGOS/LCFOS/AOS ) . We hypothesize that enteral supplementation of prebiotics may decrease infectious morbidity by reducing intestinal inflammation . Therefore , we aim ed to determine the effect of enteral supplementation of prebiotics on intestinal inflammation , as measured by fecal IL-8 ( f-IL-8 ) and calprotectin ( f-calprotectin ) , in preterm infants . In a r and omized controlled trial , infants with a GA received enteral supplementation of prebiotics or placebo ( maltodextrin ) between d 3 and 30 of life . F-IL-8 and f-calprotectin was assessed at baseline , d 7 , 14 , and 30 of life . In total , 113 infants were included . Baseline patient and nutritional characteristics were not different in the SCGOS/LCFOS/AOS ( n = 55 ) and the placebo group ( n = 58 ) . Enteral supplementation of prebiotics had no effect on f-IL-8 and f-calprotectin . F-IL-8 and f-calprotectin were strongly correlated at all time points ( p supplementation of prebiotics ( SCGOS/LCFOS/AOS ) does not affect f-IL-8 and f-calprotectin levels in preterm infants", "The addition of probiotics to infant formula has been shown to be an efficient way to increase the number of beneficial bacteria in the intestine in order to promote a gut flora resembling that of breast-fed infants . The objective of the present study was to evaluate the safety and tolerance of a combination of two probiotic strains in early infancy . A group of 126 newborns were r and omised to receive a prebiotic-containing starter formula supplemented with Lactobacillus paracasei ssp . paracasei and Bifidobacterium animalis ssp . lactis or the same formula without probiotics for the first 3 months of life . A total of eighty infants continued the study until they were aged 6 months . Growth measurements were taken monthly at healthy baby clinics . Diaries were used to monitor behaviour , infections , use of antibiotics , as well as stool characteristics . Normal growth occurred in all infants and no statistically significant differences were detected between the probiotics group and the control group for gain in weight , length and head circumference . Infants in the probiotics group produced softer and more frequent stools during the first 3 months of life . No differences were found in crying and sleeping hours , number of parent-diagnosed infections , antibiotic use , visits to the general practitioner and number of adverse events . The use of a prebiotic-containing starter formula supplemented with L. paracasei ssp . paracasei and B. animalis ssp . lactis in early infancy is safe , well tolerated and has no adverse effects on growth and infant behaviour", "ABSTRACT A healthy intestinal microbiota is considered to be important for priming of the infants ' mucosal and systemic immunity . Breast-fed infants typically have an intestinal microbiota dominated by different Bifidobacterium species . It has been described that allergic infants have different levels of specific Bifidobacterium species than healthy infants . For the accurate quantification of Bifidobacterium adolescentis , Bifidobacterium angulatum , Bifidobacterium bifidum , Bifidobacterium breve , Bifidobacterium catenulatum , Bifidobacterium dentium , Bifidobacterium infantis , and Bifidobacterium longum in fecal sample s , duplex 5′ nuclease assays were developed . The assays , targeting rRNA gene intergenic spacer regions , were vali date d and compared with conventional PCR and fluorescent in situ hybridization methods . The 5′ nuclease assays were subsequently used to determine the relative amounts of different Bifidobacterium species in fecal sample s from infants receiving a st and ard formula or a st and ard formula supplemented with galacto- and fructo-oligosaccharides ( OSF ) . A breast-fed group was studied in parallel as a reference . The results showed a significant increase in the total amount of fecal bifidobacteria ( 54.8 % ± 9.8 % to 73.4 % ± 4.0 % ) in infants receiving the prebiotic formula ( OSF ) , with a diversity of Bifidobacterium species similar to breast-fed infants . The intestinal microbiota of infants who received a st and ard formula seems to resemble a more adult-like distribution of bifidobacteria and contains relatively more B. catenulatum and B. adolescentis ( 2.71 % ± 1.92 % and 8.11 % ± 4.12 % , respectively , versus 0.15 % ± 0.11 % and 1.38 % ± 0.98 % for the OSF group ) . In conclusion , the specific prebiotic infant formula used induces a fecal microbiota that closely resembles the microbiota of breast-fed infants also at the level of the different Bifidobacterium species", "Preterm infants have an impaired gut barrier function . We aim ed to determine the effects of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( short-chain galacto-oligosaccharides (SCGOS)/long-chain fructo-oligosaccharides ( LCFOS ) ) and acidic oligosaccharides ( AOS ) on intestinal permeability of preterm infants as measured by the sugar absorption test in the first week of life . Furthermore , we determined host- and treatment-related factors associated with intestinal permeability . In a r and omised controlled trial , preterm infants with a gestational age received enteral supplementation of SCGOS/LCFOS/AOS or placebo ( maltodextrin ) between days 3 and 30 of life . Intestinal permeability , reflected by the urinary lactulose/mannitol ( L/M ) ratio after oral ingestion of lactulose and mannitol , was assessed at three time points : before the start of the study ( t = 0 ) , at day 4 ( t = 1 ) and at day 7 ( t = 2 ) of life . Data were analysed by generalised estimating equations . In total , 113 infants were included . Baseline patient and nutritional characteristics were not different between the SCGOS/LCFOS/AOS ( n 55 ) and the placebo groups ( n 58 ) . SCGOS/LCFOS/AOS had no effect on the L/M ratio between t = 0 and t = 2 . In both the groups , the L/M ratio decreased from t = 0 to t = 2 ( P . Low BW increased the L/M ratio ( P = 0·002 ) . Exclusive breast milk feeding and mixed breast milk/formula feeding during the first week of life decreased the L/M ratio ( P enteral supplementation of a prebiotic mixture does not enhance the postnatal decrease in intestinal permeability in preterm infants in the first week of life", "BACKGROUND Galactooligosaccharides ( GOS ) and long-chain fructooligosaccharides ( lcFOS ) proliferate bifidobacteria in infant gut microbiota . However , it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring . OBJECTIVES We aim ed to test how supplementation with GOS and lcFOS ( GOS/lcFOS ) in the last trimester of pregnancy affects maternal and neonatal gut microbiota . Variables of fetal immunity were assessed as a secondary outcome . DESIGN In a r and omized , double-blind , placebo-controlled pilot study , 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS ( at a ratio of 9:1 ) or maltodextrin ( placebo ) from week 25 of gestation until delivery . Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal ( days 5 , 20 , and approximately 182 ) stool sample s. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis . RESULTS The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group ( 21.0 % and 12.4 % , respectively ; P = 0.026 ) ; the proportion of lactobacilli did not differ between the groups . In neonates , bifidobacteria and lactobacilli percentages , diversity and similarity indexes , and fetal immune parameters did not differ significantly between the 2 groups . Mother-neonate similarity indexes of bifidobacteria decreased over time . CONCLUSIONS GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates . The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables", "BACKGROUND Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression . Very-low-birth-weight ( VLBW ) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life . OBJECTIVE The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance , infectious morbidity , and short-term outcome in VLBW infants . DESIGN In a double-blind r and omized controlled trial , VLBW infants ( gestational age were allocated to receive enteral glutamine supplementation ( 0.3 g . kg(-1 ) . d(-1 ) ) or isonitrogenous control supplementation ( alanine ) between days 3 and 30 of life . The supplementations were added to breast milk or to preterm formula . The primary endpoint for the study was time to full enteral feeding . Secondary endpoints were other variables of feeding tolerance , infectious morbidity , and short-term outcome . RESULTS Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented ( n = 52 ) and the control ( n = 50 ) groups . The median time to full enteral feeding was 13 d ( range : 7 - 31 d ) in the glutamine-supplemented group and 13 d ( range : 6 - 35 d ) in the control group ( hazard ratio : 1.19 ; 95 % CI : 0.79 , 1.79 ; P = 0.40 ) . In the glutamine-supplemented group , 26 of 52 infants ( 50 % ) had > /=1 serious infection compared with 38 of 50 ( 76 % ) in the control group ( odds ratio : 0.32 ; 95 % CI : 0.14 , 0.74 ; P = 0.008 ) . Other variables of feeding tolerance and short-term outcome were not significantly different between groups . CONCLUSIONS Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants . However , infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition", "In this double-blind , r and omized , placebo-controlled study , we investigated the effect of an infant milk formula with 6 g/L short-chain galacto- and long-chain fructo-oligosaccharides [ ( scGOS/lcFOS ) ratio 9:1 ] on the development of the fecal secretory immunoglobulin A ( sIgA ) response and on the composition of the intestinal microbiota in 215 healthy infants during the first 26 wk of life . The infants received breast milk or were r and omized to receive an infant milk formula with or without scGOS/lcFOS . Stool sample s were collected after 8 and 26 wk of intervention . The concentration of fecal sIgA was determined by ELISA , and the composition of the intestinal microbiota was determined by quantitative fluorescent in situ hybridization . The scGOS/lcFOS group and the control group were compared in the statistical analysis . A breast fed group was included as a reference . In total , 187 infants completed the study . After 26 wk of intervention , in infants that were exclusively formula fed , the concentration of sIgA was higher ( P percentages of bifidobacteria were higher in the scGOS/lcFOS group ( 60.4 % ) than in the control group ( 52.6 % , P = 0.04 ) . The percentages of Clostridium spp . were 0.0 and 3.27 % , respectively ( P = 0.006 ) . In conclusion , an infant milk formula with 6 g/L scGOS/lcFOS results in higher concentrations of fecal sIgA , suggesting a positive effect on mucosal immunity", "BACKGROUND Dietary nucleotides are nonprotein nitrogenous compounds that are thought to be important for growth , repair , and differentiation of the gastrointestinal tract . A higher nucleotide intake may also have favorable effects on the fecal microbial composition and incidence of diarrhea in infancy . However , few studies have tested this hypothesis with an experimental study design . OBJECTIVE We tested the hypothesis that nucleotide supplementation of infant formula has beneficial effects on fecal bacteriology . DESIGN Oligonucleotide probes were used to measure bacterial genus-specific 16S ribosomal RNA in stools of a subset of infants ( mean age : 20.4 wk ) who were r and omly assigned to nucleotide-supplemented ( 31 mg/L ; n = 35 ) or control formula ( n = 37 ) from birth until age 20 wk or were breastfed ( reference group ; n = 44 ) . The microbial pattern was assessed as the ratio of Bacteroides-Porphyromonas-Prevotella group ( BPP ) to Bifidobacterium species . RESULTS The ratio of BPP to Bifidobacterium spp . rRNA in infants r and omly assigned to the nucleotide-supplemented formula was lower than in infants receiving the control formula ( mean difference : -118 % ; 95 % CI : -203 % , -34 % ; P = 0.007 ) , but it did not differ in infants who were breastfed . The difference between r and omized formula-fed groups was independent of potential confounding factors ( P = 0.003 ) . CONCLUSIONS Our data support the hypothesis that nucleotide supplementation improves the composition of the gut microbiota in formula-fed infants . Because this effect could contribute to previously described benefits of nucleotide supplementation for gastrointestinal tract and immune function , these findings have important implication s for optimizing the diet of formula-fed infants", "A mixture of neutral short chain galactooligosaccharides and long chain fructo-oligosaccharides ( scGOS/lcFOS ) has been shown to have prebiotic and immunomodulatory effects comparable to human milk oligosaccharides . This can be translated into clinical practice as a potential to prevent infections and allergy . The hypothesis of this study was that this specific prebiotic mixture could have a preventive effect against infections during the first 6 mo of life . In a prospect i ve , r and omized , double-blind , placebo-controlled trial , healthy term infants with a parental history of atopy were fed either prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . The primary outcome measures were infectious episodes , number of infections requiring antibiotics , and incidence of infections . During the study period , infants in the scGOS/lcFOS group had fewer episodes of all types of infections combined ( P = 0.01 ) . They also tended to have fewer upper respiratory tract infection episodes ( P = 0.07 ) and fewer infections requiring antibiotic treatment ( P = 0.10 ) . Similarly , the cumulative incidence of recurring infections was significantly lower in the scGOS/lcFOS group . The cumulative incidence of any recurring infection and recurring respiratory infections was 3.9 and 2.9 % in the scGOS/lcFOS group and 13.5 and 9.6 % in the placebo group , respectively ( P Oligosaccharide prebiotics reduced the number of infectious episodes and the incidence of recurring , particularly respiratory , infections during the first 6 mo of life . Although the exact mechanism of action is under investigation , it is very likely that the immune modulating effect of this prebiotic mixture through intestinal flora modification is the principal mechanism for the observed infection prevention early in life", "BACKGROUND Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants . OBJECTIVE The objective was to evaluate infant formulas containing probiotics and synbiotics ( combinations of probiotics and prebiotics ) for safety and tolerance . DESIGN In a prospect i ve , controlled , double-blind , r and omized trial , healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 ( BL999 ) + Lactobacillus rhamnosus LPR ( LPR ) , BL999 + LPR + 4 g/L of 90 % galactooligosaccharide/10 % short-chain fructooligosaccharide ( GOS/SCFOS ) , or BL999 + Lactobacillus paracasei ST11 ( ST11 ) + 4 g/L GOS/SCFOS from . Safety and tolerance were assessed based on weight gain during the treatment period ( primary outcome ) as well as recumbent length , head circumference , digestive tolerance , and adverse events ( secondary outcomes ) , which were evaluated at 2 , 4 , 8 , 12 , 16 , and 52 wk of age . RESULTS Two hundred eighty-four infants were enrolled . During the treatment period , difference in mean weight gain between control and study formula groups in both the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d , indicating equivalent weight gain . Secondary outcomes did not show significant differences between groups during the treatment period . CONCLUSION Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well", "A mixture of neutral short-chain galactooligosaccharides ( scGOS ) and long-chain fructooligosaccharides ( lcFOS ) has been shown to reduce the incidence of atopic dermatitis ( AD ) and infectious episodes during the first 6 mo of life . This dual protection occurred through the intervention period . The present study evaluated if these protective effects were lasting beyond the intervention period . In a prospect i ve , r and omized , double-blind , placebo-controlled design , healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented ( 8 g/L scGOS/lcFOS ) or placebo-supplemented ( 8 g/L maltodextrin ) hypoallergenic formula during the first 6 mo of life . Following this intervention period , blind follow-up continued until 2 y of life . Primary endpoints were cumulative incidence of allergic manifestations . Secondary endpoints were number of infectious episodes and growth . Of 152 participants , 134 infants ( 68 in placebo , 66 in intervention group ) completed the follow-up . During this period , infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations . Cumulative incidences for AD , recurrent wheezing , and allergic urticaria were higher in the placebo group , ( 27.9 , 20.6 , and 10.3 % , respectively ) than in the intervention group ( 13.6 , 7.6 , and 1.5 % ) ( P episodes of physician-diagnosed overall and upper respiratory tract infections ( P fever episodes ( P fewer antibiotic prescriptions ( P Growth was normal and similar in both groups . Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections . The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action", "Adding prebiotics or probiotics to infant formula to improve the intestinal flora of formula-fed infants is considered to be a major innovation . Several companies have brought relevant formulations onto the market . However , comparative data on the effects of pre- and probiotics on the intestinal microflora of infants are not available . The present study aim ed to compare the effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the composition and metabolic activity of the intestinal microflora . Before birth , infants were r and omised and double blindly allocated to one of three formulas . The prebiotic ( GOS/FOS ) group ( n 19 ) received regular infant formula supplemented with a mixture of galacto-oligosaccharides and fructo-oligosaccharides ( 6 g/l ) . The probiotic ( Bb-12 ) group ( n 19 ) received the same formula supplemented with 6.0x10(10 ) viable cells of B. animalis per litre . The st and ard group ( n 19 ) received non-supplemented regular formula . A group of sixty-three breast-fed infants was included as a reference group . Faecal sample s were taken at postnatal day 5 and 10 , and week 4 , 8 , 12 and 16 . Compared with the groups fed Bb-12 and st and ard formula , the GOS/FOS formula group showed higher faecal acetate ratio ( 69.7 % ( sem 2.7 ) , 69.9 % ( sem 3.9 ) and 82.2 % ( sem 5.3 ) ; P lactate concentration ( 11.3 ( sem 7.9 ) , 3.1 ( sem 2.3 ) and 34.7 ( sem 10.7 ) mmol/kg faeces ) and lower pH ( 6.6 ( sem 0.2 ) , 7.1 ( sem 0.2 ) and 5.6 ( sem 0.2 ) ; P percentage of bifidobacteria between the GOS/FOS ( 59.2 % ( sem 7.7 ) ) , Bb-12 ( 52.7 % ( sem 8.0 ) ) and the st and ard ( 51.8 % ( sem 6.4 ) ) groups were not statistically significant at 16 weeks . Feeding infants GOS/FOS formula result ed in a similar effect on metabolic activity of the flora as in breast-fed infants . In the Bb-12 group , composition and metabolic activity of the flora were more similar to those of the st and ard group", "BACKGROUND Serious infectious morbidity is high in preterm infants . Enteral supplementation of prebiotics may reduce the incidence of serious infections , especially infections related to the gastrointestinal tract . OBJECTIVE The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ( (SC)GOS/(LC)FOS ) and acidic oligosaccharides ( AOS ) on serious infectious morbidity in preterm infants . DESIGN In a r and omized controlled trial , preterm infants ( gestational age received enteral supplementation of 80 % (SC)GOS/(LC)FOS and 20 % AOS ( 1.5 g . kg(-1 ) . d(-1 ) ) or placebo ( maltodextrin ) between days 3 and 30 of life . Serious infectious morbidity was defined as a culture positive for sepsis , meningitis , pyelonephritis , or pneumonia . The analysis was performed by intention-to-treat and per- protocol , defined as > or = 50 % supplementation dose during the study period . RESULTS In total , 113 preterm infants were included . Baseline and nutritional characteristics were not different between groups . In the intention-to-treat analysis , the incidence of > or = 1 serious infection , > or = 1 serious endogenous infection , or > or = 2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups . In the per- protocol analysis , there was a trend toward a lower incidence of > or = 1 serious endogenous infection and > or = 2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group ( P = 0.09 and P = 0.07 , respectively ) . CONCLUSIONS Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants . However , there was a trend toward a lower incidence of serious infectious morbidity , especially for infections with endogenous bacteria . This finding suggests a possible beneficial effect that should be evaluated in a larger study . This trial was registered at is rct n.org as IS RCT N16211826", "Objective : The aim of the study was to evaluate the effect of infant formula with polydextrose ( PDX ) and galacto-oligosaccharides ( GOS ) on fecal microbiota and secretory IgA ( sIgA ) . Material s and Methods : In the present double-blind , r and omized study , term infants received control ( Enfamil Lipil ) or the same formula with PDX/GOS ( 4 g/L , 1:1 ratio ; PDX/GOS ) for 60 days ; a reference breast-fed group was included . Formula intake , tolerance , and stool characteristics were collected via electronic diary and analyzed by repeated measures analysis of variance . Anthropometric measurements and stool sample s were obtained at baseline and after 30 and 60 days of feeding . Fecal sIgA was measured by enzyme-linked immunosorbent assay and fecal bacteria by fluorescent in situ hybridization and quantitative real-time polymerase chain reaction ( qPCR ) ; both were analyzed by Wilcoxon rank sum test . Results : Two hundred thirty infants completed the study . Infants consuming PDX/GOS had softer stools than control at all times ( P counts in PDX/GOS were closer to the breast-fed group , tended to be higher than control for total bifidobacteria ( P = 0.069 ) and Bifidobacterium longum ( P = 0.057 ) at 30 days , and were significantly higher for total bifidobacteria and B longum at 60 days and B infantis at 30 days ( P = 0.002 ) . No significant differences were detected between PDX/GOS and control in changes from baseline to 30 or 60 days for sIgA or total bifidobacteria by fluorescent in situ hybridization or qPCR ; however , significantly higher changes from baseline were detected between PDX/GOS and control for B infantis at 30 days and B longum at 60 days ( P ⩽ 0.035 ) . Conclusions : Infant formula with PDX/GOS produces soft stools and a bifidogenic effect closer to breast milk than formula without PDX/GOS ", "Background : Colic , regurgitation and constipation are common feeding problems in formula‐fed infants that might benefit from dietary treatment . A formula containing fructo‐ and galacto‐oligosaccharides , partially hydrolysed proteins , low levels of lactose and palmitic acid in the β position and higher density has been tested to reduce the occurrence of these symptoms . The aim of this prospect i ve study was to describe the effects of such a formula in infants with minor gastrointestinal disorders . Methods : An observational prospect i ve trial involving practising Italian paediatricians was performed . Formula fed‐infants up to 90 d of age with minor gastrointestinal problems such as infantile colics and /or regurgitation and /or constipation were enrolled in the study from January 2001 to May 2001 . The study was completed within 14 d of treatment . On days 1 , 7 and 14 the infants were visited by the paediatricians . Parents were given a structured diary to record daily episodes of colic , regurgitation and type and number of stools . Results : Of the 932 infants enrolled , 604 completed the study . Of the 214 infants with colic , 169 ( 79 % ) demonstrated a reduction in frequency of colic from 4.1 ± 2.0 per day at the beginning of the study to 2.0 ± 1.8 at the end of the study ( I.C. 95 % : 1.72–2.39 ; p reduction in the number of episodes of colic of 1.8 per day at the beginning of the study ( I.C. 95 % : 1.49–2.11 ; p 201 infants with regurgitation problems , 141 ( 70 % ) demonstrated a reduction of frequency of the symptoms from 4.2 ± 2.0 per day at the beginningof the study to 2.1 ± 2.2 at the end of the study ( I.C. 95 % : 1.75–2.35 ; p 1.87 in the number of regurgitation episodes was reported between day 1 and day 7 ( I.C. 95 % : 1.57–2.16 ; p 232 infants with constipation , 147 ( 63 % ) demonstrated an increase in the daily number of stools of 0.42 ( I.C. 95 % : 0.5–0.3 ; p increase in stool frequency of 0.41 ( I.C. 95 % : 0.51–0.23 ; p 14 . Parents’evaluation of the formula was 7.9 ± 1.8 ( score 0–10 ) ; 550 parents ( 91 % ) gave a positive judgement ( score > 6 ) . The evaluation by the paediatricians of the improvement in symptoms after the treatment was 8.2 ± 1.5 ; 574 ( 95 % ) a positive effect ( score > 6 )", "The objective of the present study was to assess the effect of adding specific prebiotics to st and ard formula feeding on the number of fever episodes in the first year of life . In the present r and omised , double-blind , placebo-controlled trial in seven centres in five West European countries , 830 healthy term infants , without a first-degree family history of allergic disease , of mothers who indicated to give only formula feeding were r and omised either to receive a st and ard non-hydrolysed cows ' milk-based formula to which a mixture of specific oligosaccharides was added ( prebiotics group ( PG ) ) , or to receive a similar formula without oligosaccharides ( control group ( CG ) ) . A separate reference group consisted of 300 breast-fed infants . The primary outcome was the number of fever episodes prospect ively documented by the parents . There was no difference in the number of fever episodes between the PG ( median value 1·19 ; 25th-75th percentile 0·09 - 2·34 ) and CG ( 1·16 ; 25th-75th percentile 0·06 - 2·38 ) . The median number of fever episodes in the separate breast-feeding reference group was 1·24 ( 25th-75th percentile 0·51 - 3·45 ) . There was no effect of adding specific prebiotics to st and ard formula feeding in reducing the number of fever episodes in the present study", "Background Nutrilon Omneo ( new formula ; NF ) contains high concentration of sn-2 palmitic acid , a mixture of prebiotic oligosaccharides and partially hydrolyzed whey protein . It is hypothesized that NF positively affects stool characteristics in constipated infants . Methods Thirty-eight constipated infants , aged 3–20 weeks , were included and r and omized to NF ( n = 20 ) or a st and ard formula ( SF ; n = 18 ) in period 1 and crossed-over after 3 weeks to treatment period 2 . Constipation was defined by at least one of the following symptoms : 1 ) defecation frequency 2 ) painful defecation ; 3 ) abdominal or rectal palpable mass . Results Period 1 was completed by 35 infants . A significant increase in defecation frequency ( NF : 3.5 pre versus 5.6/week post treatment ; SF 3.6 pre versus 4.9/week post treatment ) was found in both groups , but was not significantly different between the two formulas ( p = 0.36 ) . Improvement of hard stool consistency to soft stool consistency was found more often with NF than SF , but did not reach statistical significance ( 90 % versus 50 % ; RR , 1.8 ; 95 % CI , 0.9–3.5 ; p = 0.14 ) . No difference was found in painful defecation or the presence of an abdominal or rectal mass between the two groups . Twenty-four infants completed period 2 . Only stool consistency was significantly different between the two formulas ( 17 % had soft stools on NF and hard stools on SF ; no infants had soft stools on SF and hard stools on NF , McNemar test p = 0.046 ) . Conclusion The addition of a high concentration sn-2 palmitic acid , prebiotic oligosaccharides and partially hydrolyzed whey protein result ed in a strong tendency of softer stools in constipated infants , but not in a difference in defecation frequency . Formula transition to NF may be considered as treatment in constipated infants with hard stools", "Background : Oligosaccharides may alter postnatal immune development by influencing the constitution of gastrointestinal bacterial flora . Aims : To investigate the effect of a prebiotic mixture of galacto- and long chain fructo-oligosaccharides on the incidence of atopic dermatitis ( AD ) during the first six months of life in formula fed infants at high risk of atopy . Methods : Prospect i ve , double-blind , r and omised , placebo controlled trial ; 259 infants at risk for atopy were enrolled . A total of 102 infants in the prebiotic group and 104 infants in the placebo group completed the study . If bottle feeding was started , the infant was r and omly assigned to one of two hydrolysed protein formula groups ( 0.8 g/100 ml prebiotics or maltodextrine as placebo ) . All infants were examined for clinical evidence of atopic dermatitis . In a subgroup of 98 infants , faecal flora was analysed . Results : Ten infants ( 9.8 % ; 95 CI 5.4–17.1 % ) in the intervention group and 24 infants ( 23.1 % ; 95 CI 16.0–32.1 % ) in the control group developed AD . The severity of the dermatitis was not affected by diet . Prebiotic supplements were associated with a significantly higher number of faecal bifidobacteria compared with controls but there was no significant difference in lactobacilli counts . Conclusion : Results show for the first time a beneficial effect of prebiotics on the development of atopic dermatitis in a high risk population of infants . Although the mechanism of this effect requires further investigation , it appears likely that oligosaccharides modulate postnatal immune development by altering bowel flora and have a potential role in primary allergy prevention during infancy", "Background the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk . The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy . Methodology /Principal Findings this study was performed as a multi-center , r and omized , double-blind , placebo-controlled trial including healthy term infants . Infants were recruited before the age of 8 weeks , either having started with formula feeding or being fully breast-fed ( breastfeeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . Growth , tolerance and adverse events were assessed at 8 , 16 , 24 and 52 weeks of age . The prebiotic and control groups showed similar mean weight , length and head circumference , skin fold thicknesses , arm circumference gains and stool frequency at each study point . As far as the anthropometric parameters are concerned , the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point . The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants , whereas at 52 weeks were strikingly smaller . The stool consistency in the prebiotic group was softer than in the control group at 8 , 16 and 24 weeks ( p incidence of adverse events between the two formula groups . Conclusions our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants . Trial Registration : drks-neu.uniklinik-freiburg.de DRKS", "Background Human milk oligosaccharides have been shown to stimulate selectively the growth of Bifidobacteria and Lactobacilli in the intestine . In this study , the bifidogenic effect of an experimental prebiotic oligosaccharide mixture consisting of low-molecular-weight galactooligosaccharides and high-molecular-weight fructooligosaccharides was analyzed in 90 term infants . Methods Two test formulas were supplemented with either 0.4 g/dL or with 0.8 g/dL oligosaccharides . In the control formula , maltodextrin was used as placebo . At study day 1 and study day 28 , the fecal species , colony forming units ( cfu ) and pH were measured and stool characteristics , growth , and side effects were recorded . Results At study day 1 , the median number of Bifidobacteria did not differ among the groups ( 0.4 g/dL group , mean [ interquartile range ] 8.5 [ 1.9 ] cfu/g ; 0.8 g/dL group , 7.7 [ 6.1 ] cfu/g ; and the placebo group , 8.8 [ 6.1 ] cfu/g ) ( figures in square brackets are interquartile range ) . At the end of the 28-day feeding period , the number of Bifidobacteria was significantly increased for both groups receiving supplemented formulas ( the 0.4 g/dL group , 9.3 [ 4.9 ] cfu/g ; the 0.8 g/dL group , 9.7 [ 0.8 ] cfu/g ) versus the placebo group ( 7.2 [ 4.9 ] cfu/g , P The number of Lactobacilli also increased significantly in both groups fed the supplemented formulas ( versus placebo , P change in fecal pH ( P the stool frequency result ed in a significant difference between the placebo group and the group fed the 0.8 g/dL formula at day 28 ( P stool consistency ( 0.8 g/dL versus placebo , P incidence of side effects ( crying , regurgitation , vomiting ) or growth . Conclusions These data indicate that supplementation of a term infant 's formula with a mixture of galacto- and fructooligosaccharides has a dose-dependent stimulating effect on the growth of Bifidobacteria and Lactobacilli in the intestine and results in softer stool with increasing dosage of supplementation", "CONTEXT Sepsis is a common and severe complication in premature neonates , particularly those with very low birth weight ( VLBW ) ( Whether lactoferrin , a mammalian milk glycoprotein involved in innate immune host defenses , can reduce the incidence of sepsis is unknown . In animal models , the probiotic Lactobacillus rhamnosus GG ( LGG ) enhances the activity of lactoferrin but has not been studied in human infants . OBJECTIVE To establish whether bovine lactoferrin ( BLF ) , alone or in combination with LGG , reduces the incidence of late-onset sepsis in VLBW neonates . DESIGN , SETTING , AND PATIENTS Prospect i ve , multicenter , double-blind , placebo-controlled , r and omized trial conducted in 11 Italian tertiary neonatal intensive care units . Patients were 472 VLBW infants enrolled from October 1 , 2007 , through July 31 , 2008 , and assessed until discharge for development of sepsis . INTERVENTION Infants were r and omly assigned to receive orally administered BLF ( 100 mg/d ) alone ( n = 153 ) , BLF plus LGG ( 6 x 10(9 ) colony-forming units/d ) ( n = 151 ) , or placebo ( n = 168 ) from birth until day 30 of life ( day 45 for neonates First episode of late-onset sepsis , ie , sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid . RESULTS Demographic , clinical , and management characteristics of the 3 groups were similar , including type of feeding and intake of maternal milk . Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups ( 9/153 [ 5.9 % ] and 7/151 [ 4.6 % ] , respectively ) than in the control group receiving placebo ( 29/168 [ 17.3 % ] ) ( risk ratio , 0.34 ; 95 % confidence interval , 0.17 - 0.70 ; P = .002 for BLF vs control and risk ratio , 0.27 ; 95 % confidence interval , 0.12 - 0.60 ; P bacterial and fungal sepsis . No adverse effects or intolerances to treatment occurred . CONCLUSION Compared with placebo , BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N53107700", "Risk of allergic diseases has been linked to abnormal patterns of fetal immune development , suggesting that priming of the immune system may occur in utero . The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells ( C BMC ) shows association with allergic diseases and IgE sensitization at 2 yr of age , and to study the effect of maternal probiotic supplementation on C BMC immune responses . C BMC were isolated from 98 neonates in a r and omized double-blinded intervention study . C BMC were stimulated with beta-lactoglobulin , and phytohemaglutinin ( PHA ) . Secretion of interferon-gamma ( IFN-gamma ) , interleukin-5 ( IL-5 ) , and IL-13 was measured by an ELISA ; IL-2 , IL-4 , and IL-10 by a cytokine bead assay . T-cell polarization-associated IL-4 receptor and IL-12R expressions , and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR . The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age , and with the maternal probiotic or placebo supplementation . PHA-stimulated GATA-3 expression and IL-2 secretion in C BMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized , non-allergic children ( p = 0.03 and 0.026 ) . PHA-induced expression of GATA-3 correlated with IL-5 ( p = 0.003 , r = 0.300 ) and IL-13 ( p = 0.007 , r = 0.278 ) secretion of C BMC , and IL-5 secretion of beta-lactoglobulin-stimulated C BMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized , non-allergic children ( p = 0.013 ) . Probiotic bacteria had no effect on C BMC immune responses . In C BMC -enhanced induction of GATA-3 , which activates several Th2 cytokines genes , was a risk factor for IgE sensitization . The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens", "Background Prevention of serious infections in preterm infants is a challenge , since prematurity and low birth weight often requires many interventions and high utility of devices . Furthermore , the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system . In combination with delayed intestinal bacterial colonisation compared with term infants , this may increase the risk for serious infections . Acidic and neutral oligosaccharides play an important role in the development of the immune system , intestinal bacterial colonisation and functional integrity of the gut . This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity ( primary outcome ) , immune response to immunizations , feeding tolerance and short-term and long-term outcome in preterm infants . In addition , an attempt is made to eluci date the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut . Methods / Design In a double-blind placebo controlled r and omised trial , 120 preterm infants ( gestational age are r and omly allocated to receive enteral acidic and neutral oligosaccharides supplementation ( 20%/80 % ) or placebo supplementation ( maltodextrin ) between day 3 and 30 of life . Primary outcome is infectious morbidity ( defined as the incidence of serious infections ) . The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations , plasma cytokine concentrations , faecal Calprotectin and IL-8 . The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance , intestinal permeability , intestinal viscosity , and determining intestinal microflora . Furthermore , short-term and long-term outcome are evaluated . Discussion Especially preterm infants , who are at increased risk for serious infections , may benefit from supplementation of prebiotics . Most studies with prebiotics only focus on the colonisation of the intestinal microflora . However , the pathways how prebiotics may influence the immune system are not yet fully understood . Study ing the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants . The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system . Increased insight in the effects of prebiotics on the developing immune system may help to decrease the ( infectious ) morbidity and mortality in preterm infants . Trial registration Current Controlled Trials IS RCT N16211826", "Objectives : To come even closer to the functional composition of human milk , acidic oligosaccharides ( AOS ) from pectin were added to well known neutral prebiotics ( galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( FOS ) ) . The effect of AOS and GOS/FOS/AOS on intestinal flora , stool characteristics as well as acceptance and tolerance was investigated . Methods : Human milk contains 75 % to 85 % neutral and 15 % to 25 % acidic oligosaccharides . In this prospect i ve , r and omized , double blind study , a mixture of 80 % neutral oligosaccharides ( from long-chain galacto- and long-chain fructo-oligosaccharides ) with 20 % acidic oligosaccharides derived from pectin hydrolysis was investigated . Forty-six term infants were fed a st and ard formula supplemented with either maltodextrin as control ( n = 15 ) , or with 0.2 g acidic oligosaccharides ( n = 16 ) , or with the latter plus 0.6 g neutral oligosaccharides ( mixture of galacto- and fructo-oligosaccharides ; n = 15 ) . Fecal flora using plating technique and pH were measured . Stool characteristics and possible side effects ( crying , vomiting , and regurgitation ) were recorded . Results : There was no difference in the bifidobacteria counts between the control and the group supplemented with acidic oligosaccharides alone ( 8.75 ± 0.50 vs. 8.58 ± 0.94 log colony forming units [CFU]/g stool ) . In infants fed the combination of acidic and neutral oligosaccharides , bifidobacteria were increased ( 9.61 ± 0.70 log CFU/g stool ; P . Stool consistency was softest in infants fed the complete oligosaccharide mixture , but also in those fed formula supplemented with acidic oligosaccharides alone , the stool consistency was significantly softer compared with the control group . Fecal pH increased in the controls , remained constant in acidic oligosaccharides alone , and decreased in the complete mixture of oligosaccharides group . Conclusion : There was no difference in growth , crying , vomiting , and regurgitation patterns between the groups . In summary , acidic oligosaccharides from pectin hydrolysate are well tolerated as ingredient in infant formulae but do not affect intestinal microecology", "There is some evidence that early colonization of the intestine affects the composition of the intestinal microbiota after weaning . In the present study , the effect of prebiotics administered from the first day of life on fecal counts of bifidobacteria and lactobacilli were studied during and after the administration of the prebiotics . In this double-blind , r and omized , placebo-controlled , explorative study , 20 newborns of hepatitis C virus-infected mothers who decided not to breast feed due to their concerns regarding their plasma viral load were r and omly assigned to either a formula with 8 g/L of a specific prebiotic mixture ( short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides , ratio 9:1 ) or a formula containing the same amount of maltodextrin ( placebo ) . Clinical examination including anthropometric measurements , microbiological analysis of fecal sample s , and blood leukocyte population analysis were performed at birth and 3 , 6 , and 12 mo age . At the age of 12 mo , hepatitis B vaccine-specific IgG serum titers ( Hepatitis B virus surface antibodies ) were also measured . Prebiotic supplementation result ed in more fecal bifidobacteria ( P lactobacilli ( P = 0.0044 ) compared with the placebo group . These differences between the groups were maintained during the second half of the first year without any prebiotic supplementation . There was no influence of the different diets on anthropometric data or the measured immunological variables . The data from this small explorative study indicate that early colonization of the intestine might have long-lasting effects on the composition of the intestinal microbiota", "Background To ensure the suitability of an infant formula as the sole source of nutrition or provide benefits similar to outcomes in breastfed infants , advancements in formula composition are warranted as more research detailing the nutrient composition of human milk becomes available . This study was design ed to evaluate growth and tolerance in healthy infants who received one of two investigational cow ’s milk-based formulas with adjustments in carbohydrate , fat , and calcium content and supplemented with a prebiotic blend of polydextrose ( PDX ) and galactooligosaccharides ( GOS ) or GOS alone . Methods In this multi-center , double-blind , parallel- design ed , gender-stratified prospect i ve study 419 infants were r and omized and consumed either a marketed routine cow ’s milk-based infant formula ( Control ; Enfamil ® LIPIL ® , Mead Johnson Nutrition , Evansville , IN ) ( n = 142 ) or one of two investigational formulas from 14 to 120 days of age . Investigational formulas were supplemented with 4 g/L ( 1:1 ratio ) of a prebiotic blend of PDX and GOS ( PDX/GOS ; n = 139 ) or 4 g/L of GOS alone ( GOS ; n = 138 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age . Daily recall of formula intake , tolerance , and stool characteristics was collected during study weeks 1 and 2 and 24-h recall was collected at 60 , 90 , and 120 days of age . Medically-confirmed adverse events were recorded throughout the study . Results There were no group differences in growth rate from 14 to 120 days of age . Discontinuation rates were not significantly different among study groups . No differences in formula intake or infant fussiness or gassiness were observed . During study weeks 1 and 2 and at 60 days of age stool consistency ratings were higher ( i.e. softer stools ) for infants in the PDX/GOS and GOS groups versus Control and remained higher at 120 days for the PDX/GOS group ( all P The overall incidence of medically-confirmed adverse events was similar among groups . Conclusions Investigational routine infant formulas supplemented with 4 g/L of either a prebiotic blend of PDX and GOS or GOS alone were well-tolerated and supported normal growth . Compared to infants who received the unsupplemented control formula , infants who received prebiotic supplementation experienced a softer stooling pattern similar to that reported in breastfed infants . Trial registration Clinical Trials.gov Identifier :", "Background Enteral feeding of very low birth weight ( VLBW ) infants is a challenge , since metabolic dem and s are high and administration of enteral nutrition is limited by immaturity of the gastrointestinal tract . The amino acid glutamine plays an important role in maintaining functional integrity of the gut . In addition , glutamine is utilised at a high rate by cells of the immune system . In critically ill patients , glutamine is considered a conditionally essential amino acid . VLBW infants may be especially susceptible to glutamine depletion as nutritional supply of glutamine is limited in the first weeks after birth . Glutamine depletion has negative effects on functional integrity of the gut and leads to immunosuppression . This double-blind r and omised controlled trial is design ed to investigate the effect of glutamine-enriched enteral nutrition on feeding tolerance , infectious morbidity and short-term outcome in VLBW infants . Furthermore , an attempt is made to eluci date the role of glutamine in postnatal adaptation of the gut and modulation of the immune response . Methods VLBW infants ( gestational age are r and omly allocated to receive enteral glutamine supplementation ( 0.3 g/kg/day ) or isonitrogenous placebo supplementation between day 3 and 30 of life . Primary outcome is time to full enteral feeding ( defined as a feeding volume ≥ 120 mL/kg/day ) . Furthermore , incidence of serious infections and short-term outcome are evaluated . The effect of glutamine on postnatal adaptation of the gut is investigated by measuring intestinal permeability and determining faecal microflora . The role of glutamine in modulation of the immune response is investigated by determining plasma Th1/Th2 cytokine concentrations following in vitro whole blood stimulation", "Background : The establishment of a balanced intestinal microflora which may protect against infection is desirable for the preterm infant . Objective : To investigate the effect of a preterm formula milk supplement consisting of oligosaccharides in similar proportions to human milk on the faecal flora and stool characteristics of preterm infants . Study design : To resemble the effect of human milk , an oligosaccharide mixture consisting of 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides was used to supplement a st and ard preterm formula at a concentration of 10 g/l . This supplemented formula was studied in 15 preterm infants , and the results were compared with those found in 15 infants fed a formula supplemented with maltodextrin as placebo . A group fed fortified mother 's milk was investigated as a reference group ( n = 12 ) . On four days during a 28 day feeding period ( 1 , 7 , 14 , and 28 ) , the faecal flora was investigated , and stool characteristics , growth , and possible side effects were recorded . Results : During the study period , the number of bifidobacteria in the group fed the oligosaccharide supplemented formula increased to the upper range of bifidobacteria counts in the reference group . The difference between the supplemented and non-supplemented groups was highly significant ( p = 0.0008 ) . The stool characteristics were also influenced by the supplement : the stool frequency after 28 days was significantly lower in the control group than in the oligosaccharide supplemented group ( p = 0.0079 ) and the reference group ( p stool consistency in the control group became harder , but remained fairly stable in the other two groups . There was no effect of the different diets on the incidence of side effects ( crying , regurgitation , vomiting ) or on weight gain or length gain . Conclusion : Supplementing preterm formula with a mixture of galacto- and fructo-oligosaccharides at a concentration of 10 g/l stimulates the growth of bifidobacteria in the intestine and results in stool characteristics similar to those found in preterm infants fed human milk . Therefore prebiotic mixtures such as the one studied may help to improve intestinal tolerance to enteral feeding in preterm infants", "AIM To investigate the effect of a new infant formula supplemented with a low level ( 0.24 g/100 mL ) of galacto-oligosaccharide ( GOS ) on intestinal micro-flora ( Bifidobacteria , Lactobacilli and E. coli ) and fermentation characteristics in term infants , compared with human milk and a st and ard infant formula without GOS . METHODS Term infants ( n = 371 ) were approached in this study in three hospitals of China . All infants started breast-feeding . Those who changed to formula-feeding within 4 wk after birth were r and omly assigned to one of the two formula groups . Growth and stool characteristics , and side effects that occurred in recruited infants were recorded in a 3-mo follow-up period . Fecal sample s were collected from a sub population of recruited infants for analysis of intestinal bacteria ( culture technique ) , acetic acid ( gas chromatography ) and pH ( indicator strip ) . RESULTS After 3 mo , the intestinal Bifidobacteria , Lactobacilli , acetic acid and stool frequency were significantly increased , and fecal pH was decreased in infants fed with the GOS-formula or human milk , compared with those fed with the formula without GOS . No significant differences were observed between the GOS formula and human milk groups . Supplementation with GOS did not influence the incidence of crying , regurgitation and vomiting . CONCLUSION A low level of GOS ( 0.24 g/100 mL ) in infant formula can improve stool frequency , decrease fecal pH , and stimulate intestinal Bifidobacteria and Lactobacilli as in those fed with human milk", "Background : Human milk components , including oligosaccharides , affect the gastrointestinal flora of infants . Previous studies in adults have demonstrated that fructo-oligosaccharides increase potentially beneficial fecal bacteria , including bifidobacteria . The purpose of this study was to determine the prebiotic effect of infant formula supplemented with fructo-oligosaccharides . Methods : Healthy term infants 2 to 6 weeks of age were enrolled in a 5-week , prospect i ve , r and omized , crossover , single-site study with a nonr and omized human milk comparator group . Washout weeks preceded and followed a week of feeding with fructo-oligosaccharide-supplemented formula ( 1.5 or 3.0 g/L ) . Stool specimens were quantitatively cultured weekly for bacteroides , lactobacilli , bifidobacteria , clostridia and enterococci and were tested for Clostridium difficile toxin . Results : Seventy-two of 87 infants completed the trial ; 58 were formula fed and 14 were human milk fed . Mean counts of bifidobacteria and lactobacilli were similar in all groups at entry and no group experienced a significant change in counts with fructo-oligosaccharide supplementation . After 7 days of fructo-oligosaccharide supplementation the bifidobacteria counts were greater in the 1.5 g/L fructo-oligosaccharide formula group than in the human milk fed or 3.0 g/L fructo-oligosaccharide formula groups . Formula-fed infants had higher counts of enterococci and bacteroides before fructo-oligosaccharide supplementation , and these counts did not change after supplementation . Clostridium counts increased 7 days after supplementation in the 1.5 g/L fructo-oligosaccharide formula group ( P = 0.0356 ) . No human milk fed infants had C. difficile toxin in stools . Fructo-oligosaccharide ( 3.0 g/L ) supplementation result ed in more frequent and significantly softer stools . Conclusions : Infant formula supplemented with 1.5 or 3.0 g/L fructo-oligosaccharides was safe but had minimal effect on fecal flora and C. difficile toxin", "Objectives : The intestinal flora of breast-fed infants is generally dominated by Bifidobacteria . We aim ed to investigate whether an infant formula supplemented with galacto-oligosaccharides and fructo-oligosaccharides ( GOS/FOS ) is able to establish a bifido-dominant microflora , not only in numbers but also with respect to the metabolic activity in the colon . Methods : Two groups of infants fed infant formula with 0.8 g/100 ml GOS/FOS in a ratio of 9:1 ( OSF group ) , or control formula ( SF group ) were evaluated in a r and omised , double blind , placebo controlled intervention study . A breast-fed group was studied in parallel . At study onset and after 4 and 6 weeks , faecal sample s were examined for the number of bifidobacteria , pH , short chain fatty acids and lactate . Results : After 6 weeks , the mean proportion of bifidobacteria was significantly higher in the OSF group ( 59.6 % versus 49.5 % in the SF group ; P stool mean pH and an increased proportion of acetate and a decreased proportion of propionate . The mean pH in the OSF and SF groups were 5.7 and 6.3 , respectively ( P GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora . The changes in short chain fatty acids , lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula", "Screening of total IgE in 1189 cord blood sample s was conducted by Phadebas IgE PRIST in a one-year birth cohort 1983 - 1984 in Viborg , Denmark . 113 children with cord blood IgE levels > or = 0.5 kU/l and 138 children chosen at r and om among those with cord blood IgE levels at 5 years of age . Based upon history and physical examination a diagnosis of definite atopy or no atopy was established . Allergy ( IgE mediated ) was defined as atopic disease combined with increased total IgE levels at 5 years of age . The cumulative prevalence of atopic disease was not influenced by cord blood IgE levels or atopic predisposition . Cord blood IgE levels had a low sensitivity as a predictor of atopic disease . A statistically significant correlation between serum levels of IgE at birth and at 5 years was however found ( p elevated cord blood IgE levels developed allergic disease before 5 years of age ( p total IgE level > 63 kU/l ( geometric mean + 1 SD ) at the age of 5 years can be regarded as being an elevated level . A cord blood IgE level > or = 0.3 kU/l in combination with atopic predisposition was predictive of allergic disease , especially allergic bronchial asthma . With regard to allergic disease , the positive predictive value was 26 % , the sensitivity 33 % and the rate ratio for development of allergic disease 4 . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Prebiotic-containing infant formula may beneficially affect gastrointestinal tolerance and commensal microbiota composition . OBJECTIVE Assess gastrointestinal tolerance and fecal microbiota , pH , and short-chain fatty acid ( SCFA ) concentrations of infants consuming formula with or without prebiotics . DESIGN Full-term formula-fed infants were studied to a breastfed comparison group ( BF ) . Formula-fed infants ( FF ) were r and omized to consume a partially hydrolyzed whey formula with ( PRE ) or without ( CON ) 4 g/L of galacto-oligosaccharides and fructo-oligosaccharides ( 9:1 ) . Fecal bacteria , pH , and SCFA were assessed at baseline , 3 weeks , and 6 weeks . Caregivers of patients recorded stool characteristics and behavior for 2 days before the 3- and 6-week visits . RESULTS Feces from infants fed PRE had a higher absolute number ( P = .0083 ) and proportion ( P = .0219 ) of bifidobacteria than CON-fed infants and did not differ from BF . BF had a higher proportion of bifidobacteria than CON ( P = .0219 ) and lower number of Clostridium difficile than FF ( P = .0087 ) . Feces from formula-fed infants had higher concentrations of acetate ( P ( P ( P = .0230 ) than BF ; however , fecal pH was lower ( P = .0161 ) in PRE and BF than CON . Prebiotic supplementation did not alter stool patterns , tolerance , or growth . BF had more frequent stools that were yellow ( P liquid than FF ( P well tolerated , increased abundance and proportion of bifidobacteria , and reduced fecal pH in healthy infants", "BACKGROUND The intestinal microflora is a likely source for the induction of immune deviation in infancy . OBJECTIVE The purpose of this study was to prospect ively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases . METHODS Newborn infants were followed prospect ively through the first 2 years of life in Estonia ( n = 24 ) and Sweden ( n = 20 ) . By that age , 9 Estonian and 9 Swedish infants had developed atopic dermatitis and /or positive skin prick test results . Stool sample s were obtained at 5 to 6 days and at 1 , 3 , 6 , and 12 months , and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of st and ard methods . RESULTS In comparison with healthy infants , babies who developed allergy were less often colonized with enterococci during the first month of life ( 72 % vs 96 % ; P bifidobacteria during the first year of life ( 17 % to 39 % vs 42 % to 69 % ; P counts of clostridia at 3 months ( median value , 10.3 vs 7.2 log(10 ) ; P prevalence of colonization with Staphylococcus aureus was also higher at 6 months ( 61 % vs 23 % ; P counts of Bacteroides were lower at 12 months ( 9.9 vs 10.6 log(10 ) ; P infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy . Because the observations were made in 2 countries with different st and ards of living , we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy", "Objective : Very low birth weight ( VLBW ) infants receiving glutamine-enriched enteral nutrition may present with a lower infection rate , which may result from enhanced antimicrobial innate or Th1 cytokine responses . We investigated whether glutamine-enriched enteral nutrition in VLBW infants increased these cytokine responses following in vitro stimulation of whole blood cells . Methods : In a double-blind , placebo-controlled , r and omized controlled trial , VLBW infants ( gestational age received enteral glutamine supplementation ( 0.3 g · kg−1 · day−1 ) or isonitrogenous placebo supplementation ( alanine ) between days 3 and 30 of life . Cytokine responses following in vitro whole blood cell stimulation with anti-(α)CD3/αCD28 or lipopolysaccharide were analyzed by cytometric bead array at 3 time points : before the start of the study , at day 7 of life , and at day 14 of life . Results : Baseline patient and nutritional characteristics were not different between groups . At least 2 blood sample s were analyzed in 25 of 52 ( 48 % ) and 38 of 50 ( 76 % ) infants in the glutamine-supplemented and control groups , respectively . Glutamine-enriched enteral nutrition was not associated with significant alterations in cytokine responses ( interferon-γ , tumor necrosis factor-α , interleukin [IL]-2 , IL-4 , IL-5 , and IL-10 ) of peripheral blood cells upon stimulation with either anti-αCD3/αCD28 or lipopolysaccharide . Conclusions : We hypothesize that glutamine-enriched enteral nutrition decreases the infection rate in VLBW infants by influencing the mucosal and not the systemic immune system", "AIM The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various components of breast milk , including prebiotic substances . This prospect i ve double-blind study compared the numbers of bifidobacteria in the stool flora of bottle-fed preterm infants r and omized to receive for 14 days either a formula with prebiotic fructo-oligosaccharides at a concentration of 0.4 g/dL or the same formula with maltodextrin as a placebo . METHODS Within 0 - 14 days after birth , 56 healthy bottle-fed infants were enrolled to receive either the prebiotic or placebo . Faecal sample s were taken at inclusion day and at study day 7 . The number of bifidobacteria in the stools , stool characteristics and somatic growth were recorded during the study . RESULTS In the group fed fructo-oligosaccharides , both the numbers of bifidobacteria in the stools and the proportion of infants colonized with them were significantly higher as compared to the placebo group ( p=0.032 and p=0.030 respectively ) . There was also a higher number of bacteroids in the fructo-oligosaccharide group as compared to the placebo ( p=0.029 ) . At the same time , reduction was noted in the numbers of Escherichia coli and enterococci . ( p=0.029 , and p=0.025 , respectively ) . Supplementation had also significant influence on stool frequency per day ( p=0.0080 ) . CONCLUSION An infant formula containing a small quantity of prebiotic oligosaccharides is well accepted and leads to rapid growth of bifidobacteria in the gut of bottle-fed preterm infants while decreasing the numbers of pathogenic microorganisms", "Prebiotic oligosaccharides influence the intestinal microbiota and can positively modulate the infant 's immune system . It was demonstrated that a special prebiotic mixture ( Immunofortis ( ® ) ) of short-chain galacto-oligosaccharides ( scGOS ) and long-chain fructo-oligosaccharides ( lcFOS ) can reduce the cumulative incidence of atopic dermatitis ( AD ) in infants at risk for allergy as determined using the AD symptom score ( SCORAD ) . Additionally , it was shown very recently that immunoglobulin free light-chain ( Ig-fLC ) might be involved in the pathophysiology of allergic disease . Increased Ig-fLC concentrations were found in patients suffering from AD , cow 's milk allergy , allergic rhinitis , or asthma . In this study , the effect of supplementation of scGOS/lcFOS on the Ig-fLC plasma concentrations in infants at risk for allergy was assessed . The plasma kappa and lambda Ig-fLC concentrations were measured in a double-blind , placebo-controlled , r and omized trial , in which infants at risk for developing allergic disease received a hypoallergenic whey formula containing 8 g/l of the scGOS/lcFOS mixture ( n = 34 ) or maltodextrin as a placebo ( n=40 ) for 6 months . After intervention , plasma sample s were collected , and total plasma concentrations of lambda and kappa Ig-fLC were analyzed using ELISA . Total kappa and lambda Ig-fLC plasma concentrations were higher in infants suffering from AD when compared to infants without any sign of AD . In infants receiving the prebiotic mixture , the Ig-fLC levels were significantly lower compared to the placebo-fed infants ( p Interestingly , lambda Ig-fLC concentrations were positively correlated with total IgE ( p specific scGOS/lcFOS mixture lowered kappa and lambda Ig-fLC plasma concentrations in infants at high risk for allergies when compared to infants receiving placebo formula . Because Ig-fLC concentrations were increased in infants suffering from AD , this may have contributed , at least in part , to the reduced incidence in AD as described previously . This suggests a possible role for Ig-fLC in the pathophysiology of AD in infants at risk for allergy development", "Objectives : Regarding safety , we investigated the effect of prenatal probiotic and 6 months of pro- and prebiotic supplementation of infants on their hematologic values at 6 months and 2 years and factors affecting these values . Patients and Methods : In a prospect i ve r and omized controlled probiotic intervention trial in infants at high risk for allergy , we obtained blood sample s consecutively from 98 infants at 6 months and from 658 children at 2 years to measure hematologic values . We collected fecal sample s at 3 and 6 months to measure immunologic development by calprotectin , α-1-antitrypsin , tumor necrosis factor-α , and immunoglobulin A. Results : At 6 months , infants in the probiotic group had significantly lower hemoglobin ( Hb ) values than did the placebo group , mean ( SD ) : 119.8 g/L ( 6.3 ) versus 123.3 g/L ( 8.4 ) , P = 0.025 . Adjustment for factors that might affect Hb values ( breast-feeding duration , solid-food introduction , and sex ) , revealed no need for adjustment . A significant negative correlation emerged between Hb values at 6 months and fecal calprotectin at age 3 months r = −0.301 , P = 0.009 , which was affected neither by breast-feeding , sex , nor study group . At 2 years , hematologic values in both groups became similar . Conclusions : Probiotics cause a gut mucosal inflammation with decreased Hb values during intervention , corrected after halting the supplementation", "To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk . The aim of this study was to evaluate the effects of prebiotic , probiotic added to a st and ard formula on gastrointestinal motility respect to placebo-formula . Cutaneous electrogastrography ( EGG ) and ultrasound gastric emptying ( GE ) were performed in 49 preterm newborns . 17 newborns were exclusively breast-fed ; 32 were r and omly assigned to receive prebiotic-added formula ( 0.8 g/dl of a mixture from scGOS and lcFOS , ratio 9:1 ) ( 10 ) , a probiotic-added formula ( L. reuteri at dose of 1x10(8 ) colony forming units ( CFU ) per day ) ( 10 ) , a formula with placebo ( 12 ) for 30 days . No difference was seen in the nutritional parameters and no adverse events were reported . After the intervention period , the prebiotic , probiotic , and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group ( ANOVAon ranks p control : prebiotic , probiotic and breast-milk vs placebo formula p prebiotic , probiotic and breast-milk vs placebo formula p preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk", "Breast milk prebiotic oligosaccharides are believed to promote enteral tolerance . Many mothers delivering preterm are unable to provide sufficient milk . We conducted a multicenter , r and omized , controlled trial comparing preterm formula containing 0.8 g/100 mL short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in a 9:1 ratio and an otherwise identical formula , using formula only to augment insufficient maternal milk volume . Infants were r and omized within 24 h of birth . The primary outcome ( PO ) was time to establish a total milk intake of 150 mL/kg/d PO and the principal secondary outcome ( PSO ) was proportion of time between birth and 28 d/discharge that a total milk intake of ≥150 mL/kg/d was tolerated . Other secondary outcomes included growth , fecal characteristics , gastrointestinal signs , necrotizing enterocolitis , and bloodstream infection . Outcomes were compared adjusted for prespecified covariates . We recruited 160 infants appropriately grown for GA There were no significant differences in PO or PSOs . After covariate adjustment , we showed significant benefit from trial formula in PSO with increasing infant immaturity ( 2.9 % improved tolerance for a baby born at 28-wk gestation and 9.9 % at 26-wk gestation ; p 31-wk gestation . Prebiotic supplementation appears safe and may benefit enteral tolerance in the most immature infants", "AIM To investigate whether a mixture of prebiotic non-digestible oligosaccharides ( GosFos ; referring to galacto- and fructo-oligosaccharides ) would improve feeding tolerance in preterm infants on full enteral formula feeding . We hypothesized that GosFos would : ( 1 ) reduce stool viscosity and ( 2 ) accelerate gastrointestinal transport . METHODS In a placebo-controlled double-blind trial 20 preterm infants on full enteral nutrition ( gestational age 27 ( 24 - 31 ) weeks , postnatal age 42 ( 11 - 84 ) days , and weight at study entry 1570 ( 1080 - 2300 ) g were r and omly allocated to have their feedings supplemented with either GosFos ( 1 g/100 mL ) or placebo for 14 days . Stool viscosity was measured by high-pressure capillary rheometry . Gastrointestinal transport time was assessed as the time from feeding carmine red to its appearance in the diaper . The hypotheses were tested as a priori ordered hypotheses . Data are shown as median ( range ) . RESULTS Birth weight , gestational age , postnatal age , and weight at study entry did not differ between groups . GosFos significantly reduced both stool viscosity , as measured by extrusion force ( 32 ( 2 - 67 ) versus 158 ( 24 - 314 ) N ) , and gastrointestinal transit time ( 12 ( 4 - 33 ) versus 26 ( 5 - 52 ) h ) . No adverse effects were observed . CONCLUSION Formula supplementation with GosFos reduced stool viscosity and accelerated gastrointestinal transport . Further trials are required to investigate whether GosFos facilitates enteral feeding advancement and early enteral nutrition thereby eventually reducing the incidence of catheter-related nosocomial infections and improving long-term outcome", "Probiotics are immunomodulatory and may thus affect vaccine antibody responses . With the accumulating evidence of their health-promoting effects , probiotics are increasingly administered in allergy-prone infants . Therefore , we studied the effect of probiotics on antibody responses to diphtheria , tetanus and Haemophilus influenzae type b ( Hib ) vaccines in 6-month-old infants participating in a r and omized placebo-controlled double-blind allergy-prevention trial . Mothers of unborn children at increased risk for atopy used a combination of four probiotic strains , or a placebo , for 4 wk before delivery . During 6 months from birth , their infants received the same probiotics and galacto-oligosaccharides , or a placebo . The infants were immunized with a DTwP ( diphtheria , tetanus and whole cell pertussis ) at ages 3 , 4 , and 5 months , and with a Hib polysaccharide conjugate at 4 months . Serum diphtheria , tetanus , and Hib IgG antibodies were measured at 6 months . In the probiotic group , protective Hib antibody concentrations ( > /=1 microg/ml ) occurred more frequently , 16 of 32 ( 50 % ) vs. six of 29 ( 21 % ) ( p = 0.020 ) , and the geometric mean ( inter-quartile range ) Hib IgG concentration tended to be higher 0.75 ( 0.15 - 2.71 ) microg/ml than in the placebo group 0.40 ( 0.15 - 0.92 ) microg/ml ( p = 0.064 ) . In these respective groups , diphtheria , 0.38 ( 0.14 - 0.78 ) vs. 0.47 ( 0.19 - 1.40 ) IU/ml ( p = 0.449 ) , and tetanus , 1.01(0.47 - 1.49 ) vs. 0.81 ( 0.56 - 1.39 ) IU/ml ( p = 0.310 ) , IgG titers were comparable . In conclusion , in allergy-prone infants probiotics seem not to impair antibody responses to diphtheria , tetanus , or Hib , but may improve response to Hib immunization", "BACKGROUND & AIM The addition of prebiotics to infant formula modifies the composition of intestinal microflora . Aim of the study was to test the hypothesis that prebiotics reduce the incidence of intestinal and respiratory infections in healthy infants . METHODS A prospect i ve , r and omized , placebo-controlled , open trial was performed . Healthy infants were enrolled and r and omized to a formula additioned with a mixture of galacto- and fructo-oligosaccharides or to a control formula . The incidence of intestinal and respiratory tract infections and the anthropometric measures were monitored for 12 months . RESULTS Three hundred and forty two infants ( mean age 53.7+/-32.1 days ) were enrolled . The incidence of gastroenteritis was lower in the supplemented group than in the controls ( 0.12+/-0.04 vs. 0.29+/-0.05 episodes/child/12 months ; p=0.015 ) . The number of children with more than 3 episodes tended to be lower in prebiotic group ( 17/60 vs. 29/65 ; p=0.06 ) . The number of children with multiple antibiotic courses/year was lower in children receiving prebiotics ( 24/60 vs. 43/65 ; p=0.004 ) . A transient increase in body weight was observed in children on prebiotics compared to controls during the first 6 months of follow-up . CONCLUSIONS Prebiotic administration reduce intestinal and , possibly , respiratory infections in healthy infants during the first year of age", "AIM Effects of supplementing prebiotic oligosaccharides to formula for healthy infants were studied in this placebo controlled , r and omised , double blind study . METHODS Ninety-seven infants were included into the study ; among them 42 breast-fed infants , 14 infants fed formula supplemented with 0.4 g/100ml oligosaccharides ( 9 to 1 mixture of galacto- and fructooligosaccharides ) and 13 infants fed control formula were followed-up throughout the 12-week-long study period . The groups receiving formula were compared with statistical methods , whereas data of breast-fed infants served as reference values . RESULTS Infants fed the two formulae did not differ in nutrient intakes , growth , occurrence rate of feeding difficulties and atopic manifestations , or in calcium excretion . The intestinal flora did not differ between the two formula fed groups at the beginning of the study . In contrast , numbers of Bifidobacteriae were significantly higher in infants receiving the formula supplemented with prebiotic oligosaccharides both at the 14th day ( 9 x 1011 versus 5 x 1010 , colony forming units/g faeces , median , p infant formula with prebiotic oligosaccharides result ed in ameliorating the difference in intestinal flora between formula fed and breast-fed healthy infants", "Objectives : The aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins , prebiotic oligosaccharides ( OS ) , with a high β-palmitic acid content . Design : Prospect i ve r and omized controlled study . Setting : Italy . Subjects : Two hundred and sixty-seven formula-fed infants , aged less than 4 months , with infantile colic , were r and omized to receive either the new infant formula ( study treatment ( ST ) ) or a st and ard formula and simethicone ( 6 mg/kg twice a day ) ( control treatment ( CT ) ) . A question naire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time . Results : Out of the 199 infants who completed the study , 96 were treated with the new formula and 103 were not treated . Infants receiving the new formula had a significant decrease in colic episodes after 1 week ( 2.47±1.94 at day 7 vs 5.99±1.84 at the study entry ) compared to infants receiving the CT ( 3.72±1.98 at day 7 vs 5.41±1.88 at the study entry ) ( P the crying episodes were significantly different between the two groups of infants ( 1.76±1.60 in ST vs 3.32±2.06 in CT ) ( P partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a st and ard formula and simethicone . Sponsorship : The study was supported by funds from Numico , Italy", "BACKGROUND Most infants developing atopic dermatitis have a low risk for atopy . Primary prevention of atopic dermatitis is difficult . OBJECTIVE To assess the effect of supplementation of an infant and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life . METHODS Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks , either having started with formula feeding or being on full breast-feeding ( breast-feeding group ) . Formula-fed infants were r and omized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides ( prebiotic formula group ) or regular formula without oligosaccharides ( control formula group ) . RESULTS A total of 414 infants were r and omized to the prebiotic group and 416 infants to the control group . A total of 300 infants were followed in the breast-feeding group . Up to the first birthday , atopic dermatitis occurred in significantly fewer infants from the prebiotic group ( 5.7 % ) than from the control group ( 9.7 % ; P = .04 ) . The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group ( 7.3 % ) . In a Cox regression model , the rate of atopic dermatitis was significantly lower by 44 % in the prebiotic group versus the control group ( P = .04 ) . The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants . CONCLUSION Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants", "Objectives The aim of this study was to evaluate the nutritional efficacy and bifidogenic characteristics of a new infant formula containing partially hydrolyzed whey protein , modified vegetable oil with a high & bgr;-palmitic acid content , prebiotic oligosaccharides , and starch . Methods In a double-blind study , healthy formula-fed term infants aged younger than 2 weeks were r and omized to receive either the new infant formula ( NF ) or a st and ard formula ( SF ) until the age of 12 weeks . Anthropometric measurements were taken at enrollment , 6 weeks , and 12 weeks . In a sub sample of infants , blood sample s were taken at 6 weeks and stool sample s were taken at enrollment and 6 weeks . Blood sample s were analyzed for biochemical measures of protein status and amino acids , and stools were analyzed for total bacteria and bifidobacteria . Mothers completed a feeding diary and question naire at 6 and 10 weeks . Results One hundred fifty-four infants were enrolled in the study ; 102 completed the trial . The growth of infants in both formula groups was in line with published growth curves . During the first 6 weeks , NF girls gained more weight and head circumference than the SF girls . These velocity differences were not maintained throughout the 12-week study period . The NF stools had a higher proportion of bifidobacteria at 6 weeks compared with the SF stools , and they were softer . There were no clinical ly significant differences in the blood biochemical and amino acid values between groups . Both formulas were well tolerated by the infants . Conclusions When compared with a st and ard infant formula , the new formula supported satisfactory growth , led to higher counts of bifidobacteria in the feces , produced blood bio-chemical values typical of formula-fed infants , and was well tolerated", "OBJECTIVES The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants . We assessed the safety and tolerability of an experimental formula containing 2 x 10(7 ) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90 % galacto-oligosaccharides and 10 % fructo-oligosaccharides . METHODS A 7-mo prospect i ve , r and omized , reference-controlled , double-blinded trial was performed in infants who were not breast fed after the 14th day of birth . One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old . Mean weight gain ( primary outcome ) and recumbent length , head circumference , tolerability ( gastrointestinal symptoms ) , and overall morbidity ( secondary outcomes ) were measured at 14 , 28 , 56 , 84 , and 112 d of age . RESULTS Equivalence in mean weight gain between the two groups was shown . The treatment difference in the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d . No statistically significant difference in recumbent length , head circumference , or incidence of adverse events was found between the two groups . Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well . Furthermore , these infants showed a trend toward fewer respiratory tract infections . CONCLUSIONS The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated", "Objectives : This r and omized controlled trial involving 110 healthy neonates studied physiological and bifidogenic effects of galactooligosaccharides ( GOS ) , oligofructose , and long-chain inulin ( fructooligosaccharides , FOS ) in formula . Methods : Subjects were r and omized to Orafti Synergy1 ( 50 oligofructose:50 FOS ) 0.4 g/dL or 0.8 g/dL , GOS : FOS ( 90:10 ) 0.8 g/dL , or a st and ard formula according to Good Clinical Practice guidelines . A breast-fed group was included for comparison . Outcome parameters were weight , length , intake , stool characteristics , crying , regurgitation , vomiting , adverse events , and fecal bacterial population counts . Statistical analyses used nonparametric tests . Results : During the first month of life , weight , length , intake , and crying increased significantly in all of the groups . Regurgitation and vomiting scores were low and similar . Stool frequency decreased significantly and similarly in all of the formula groups but was lower than in the breast-fed group . All of the prebiotic groups maintained soft stools , only slightly harder than those of breast-fed infants . The st and ard group had significantly harder stools at weeks 2 and 4 compared with 1 ( P total number of fecal bacteria increased in all of the prebiotic groups ( 9.82 , 9.73 , and 9.91 to 10.34 , 10.38 , and 10.37 , respectively , log10 cells/g feces , P = 0.2298 ) and more closely resembled the breast-fed pattern . Numbers of lactic acid bacteria , bacteroides , and clostridia were comparable . In the SYN1 0.8 g/dL and GOS : FOS groups , Bifidobacterium counts were significantly higher at D14 and 28 compared with D3 and were comparable with the breast-fed group . Tolerance and growth were normal . Conclusions : Stool consistency and bacterial composition of infants taking SYN1 0.8 g/dL or GOS : FOS – supplemented formula were closer to the breast-fed pattern . There was no risk of dehydration", "The aim of the study was to evaluate whether supplementation of milk-formulas with prebiotic fructo-oligosaccharides or a probiotic , Lactobacillus johnsonii La1 ( La1 ) , could modulate the composition of the fecal microbiota of formula-fed infants , compared to breastfed ( BF ) infants . Ninety infants close to 4 months of age were r and omized into one of three groups to be blindly assigned to receive for 13 weeks : a ) an infant formula ( Control ) , b ) the same formula with fructo-oligosaccharides ( Prebio ) , or c ) with La1 ( Probio ) . At the end of this period , all infants received the control formula for 2 additional weeks . Twenty-six infants , breastfed throughout the study , were recruited to form group BF . Fecal sample s were obtained upon enrolment and after 7 and 15 weeks . Bacterial population s were assessed with classical culture techniques and fluorescent in situ hybridisation ( FISH ) . Seventy-six infants completed the study . On enrolment , higher counts of Bifidobacterium and Lactobacillus and lower counts of enterobacteria were observed in BF compared to the formula-fed infants ; these differences tended to disappear at weeks 7 and 15 . No major differences for Clostridium , Bacteroides or Enterococcus were observed between the groups or along the follow up . Probio increased fecal Lactobacillus counts ( p excreted live La1 in their stools at week 7 but only 17 % at week 15 . Increased Bifidobacterium counts were observed at week 7 in the 3 formula groups , similar to BF infants . These results confirm the presence of higher counts of bifidobacteria and lactobacilli in the microbiota of BF infants compared to formula-fed infants before dietary diversification , and that La1 survives in the infant digestive tract", "Objectives : The primary objective of this study was to determine the bifidogenic effect of galacto-oligosaccharides ( GOS ) in a follow-on formula and the effects on other intestinal bacteria . Secondary objectives were the effects on stool characteristics , growth , and general well-being . Participants and Methods : In a multicenter , double-blind study , 159 healthy infants , formula-fed at enrollment ( at 4–6 months ) , were r and omized to an experimental follow-on formula supplemented with 5 g/L ( GOS ) ( 77 infants ) , or to a st and ard follow-on formula ( control , 82 infants ) . Infants were evaluated at enrollment ( study day 1 = sd1 ) , after 6 weeks ( study day 2 = sd2 ) , and after an additional 12 weeks ( study day 3 = sd3 ) . At each study day , a fresh stool sample for the bacterial counts was collected , and the growth parameters were measured . At sd2 , urinary specimens were collected for the evaluation of urinary osmolarity . Results : At sd2 and sd3 , the GOS group had a higher median number ( colony-forming units per gram of stool ) of bifidobacteria than did the control group ( sd2 GOS 9.2 × 109 vs control 4.4 × 109 , P = 0.012 ) ; ( sd3 GOS 7.2 × 109 vs control 2.4 × 109 , P = 0.027 ) . Other bacteria did not show any significant differences between the 2 groups at all study days . The GOS produced softer stools but had no effect on stool frequency . The urinary osmolarity ( mOsm/L ) at sd2 was comparable in both groups . Supplementation had no influence on the incidence of gastrointestinal side effects or on the growth of the infants . Conclusions : These data indicate that the addition of GOS ( 5 g/L ) to a follow-on formula positively influences the bifidobacteria flora and the stool consistency in infants during the supplementation period at weaning . No local or systemic side effects were recorded", "Development of oral tolerance and its stimulation by probiotics are still incomprehensible . Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA , which participates in antigen elimination . In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema , food allergy , asthma , and rhinitis ( allergic diseases ) . We performed a nested unmatched case-control study of 237 infants participating in a r and omized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth . We measured faecal IgA , alpha1-antitrypsin ( alpha1-AT ) , tumour necrosis factor-alpha ( TNF-alpha ) , and calprotectin at the age of 3 and 6 months . By age 2 yr , 124 infants had developed allergic disease or IgE-sensitization ( cases ) and 113 had not ( controls ) . In infants with high faecal IgA concentration at the age of 6 months , the risk of having any allergic disease before the age of 2 yr tended to reduce [ odds ratio ( OR : 0.52 ) ] and the risk for any IgE-associated ( atopic ) disease reduced significantly ( OR : 0.49 ) . High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr ( OR : 0.49 ) . All faecal inflammation markers ( alpha1-AT , TNF-alpha , and calprotectin ) correlated positively with faecal IgA ( p Probiotics tended to augment faecal IgA ( p = 0.085 ) and significantly increased faecal alpha1-AT ( p = 0.001 ) . High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases", "BACKGROUND : Dietary nucleotides are nonprotein nitrogenous compounds that are found in high concentrations in breast milk and are thought to be conditionally essential nutrients in infancy . A high nucleotide intake has been suggested to explain some of the benefits of breastfeeding compared with formula feeding and to promote infant growth . However , relatively few large-scale r and omized trials have tested this hypothesis in healthy infants . OBJECTIVE : We tested the hypothesis that nucleotide supplementation of formula benefits early infant growth . PATIENTS AND METHODS : Occipitofrontal head circumference , weight , and length were assessed in infants who were r and omly assigned to groups fed nucleotide-supplemented ( 31 mg/L ; n = 100 ) or control formula without nucleotide supplementation ( n = 100 ) from birth to the age of 20 weeks , and in infants who were breastfed ( reference group ; n = 101 ) . RESULTS : Infants fed with nucleotide-supplemented formula had greater occipitofrontal head circumference at ages 8 , 16 , and 20 weeks than infants fed control formula ( mean difference in z scores at 8 weeks : 0.4 [ 95 % confidence interval : 0.1–0.7 ] ; P = .006 ) even after adjustment for potential confounding factors ( P = .002 ) . Weight at 8 weeks and the increase in both occipitofrontal head circumference and weight from birth to 8 weeks were also greater in infants fed nucleotide-supplemented formula than in those fed control formula . CONCLUSIONS : Our data support the hypothesis that nucleotide supplementation leads to increased weight gain and head growth in formula-fed infants . Therefore , nucleotides could be conditionally essential for optimal infant growth in some formula-fed population s. Additional research is needed to test the hypothesis that the benefits of nucleotide supplementation for early head growth , a critical period for brain growth , have advantages for long-term cognitive development", "BACKGROUND Oligosaccharides in human milk may protect infants by improving the intestinal micro-flora and fermentation . This study was to investigate effects of infant formula milk consisting of galacto-oligosaccharide ( GOS ) on intestinal microbial population s and the fermentation characteristics in term infants in comparison with that of human milk . METHODS The test formula ( Frisolac H , Friesl and , Netherl and ) was supplemented with GOS at a concentration of 0.24 g/dl . Human milk and another formula without oligosaccharides ( Frisolac H , Friesl and , Netherl and ) were used as positive and negative control respectively . Growth , stool characteristics , and side effects of the recruited infants were recorded after 3 and 6 months ' follow-up , and the fecal species were collected for the analysis of intestinal micro-flora , short chain fatty acid ( SCFA ) and pH. RESULTS At the end of 3- and 6-month feeding period , intestinal Bifidobacteria and Lactobacilli were significantly increased in infants fed with GOS supplemented formula and human milk when compared with infants fed with negative control formula ; however , there was no statistically significant difference between GOS supplemented formula and human milk groups . Stool characteristics were influenced by the supplement and main fecal SCFA ( acetic ) , and stool frequency were significantly increased in infants fed with GOS supplemented formula and human milk , while the fecal pH was significantly decreased as compared with that of negative control ( P incidence of side effects ( including crying , regurgitation and vomiting ) . CONCLUSIONS Supplementing infant formula with GOS at a concentration of 0.24 g/dl stimulates the growth of Bifidobacteria and Lactobacilli in the intestine and stool characteristics are similar to in term infants fed with human milk ", "BACKGROUND The intestinal flora of breast-fed infants is generally dominated by bifidobacteria which have beneficial properties . Their presence is due to various compounds of breast milk including prebiotic substances . AIM This prospect i ve , double blind , study compared the growth , acceptability and the proportion of bifidobacteria and clostridia in the stool flora of bottle-fed infants r and omized to receive a formula with a specific mixture of 0.4 g/100 ml prebiotic galacto- and long-chain fructooligosaccharides or the same formula without added prebiotics . METHODS Within 0 - 14 days after birth at term , healthy bottle-fed infants were enrolled to receive either a prebiotic formula or a st and ard formula . At recruitment anthropometric measurements were done . These were repeated at the age of 6 and 12 weeks . Stool sample s were taken at inclusion and at the age of 6 weeks . The number of bifidobacteria and clostridia was determined by fluorescent in situ hybridization . RESULTS There was good tolerance of the prebiotic formula . Somatic growth was similar in the two groups . Stool frequency was significantly higher in the prebiotic group ( P=0.031 ) . Infants in the prebiotic group had also softer stools as compared to the control group ( P=0.026 ) . Baseline values of microorganisms at study entry were similar . The percentage of faecal clostridia at the completion of the study was significantly lower in the prebiotic group ( P=0.042 ) , while the proportion of faecal bifidobacteria was higher in the prebiotic group as compared to the control group . However this difference did not reach statistical significance ( P=0.262 ) . The percentage of E. coli was lower in the prebiotic group but again this did not reach statistical significance ( P=0.312 ) . CONCLUSION An infant formula containing prebiotic oligosaccharides is well tolerated , leads to normal somatic growth and suppresses the numbers of clostridia in the faeces with a trend for higher percentage of stool bifidobacteria and lower percentage of E. coli", "Objectives : Breast-fed infants have relatively high proportions of faecal bifidobacteria . This bifidogenic microbiota is at least partly explained by the high levels of prebiotic oligosaccharides in human milk . The present study aim ed at testing the effect of solid foods with added prebiotic galacto- and fructo-oligosaccharides ( GOS/FOS ) on the composition of the intestinal microbiota of fully formula-fed infants during the weaning period . Methods : The study was a double-blind , r and omised trial with an intervention period of 6 weeks . Infants aged 4 to 6 months who were about to start consuming solid foods were r and omised to receive either weaning products with a mixture of GOS/FOS or control weaning products with maltodextrin . After an adjustment period , the presented daily dose of GOS/FOS was 4.5 g. Total numbers of bacteria and bifidobacteria in faecal sample s were analysed with fluorescent in situ hybridization . Results : Thirty-five infants were included in the study , and 20 infants were included in a per- protocol analysis . In the GOS/FOS group , the faecal percentage of bifidobacteria significantly increased from 43 % to 57 % ( P = 0.031 ) from week 0 to week 6 , but did not significantly change in the control group ( 36 % and 32 % , respectively ; P = 0.387 ) . The change in the percentage of bifidobacteria between week 0 and week 6 in the GOS/FOS was significantly different from this change in the control group ( P = 0.026 ) . Conclusions : We conclude that addition of GOS/FOS to solid foods induces an increase in the faecal proportion of bifidobacteria in the intestinal microbiota of fully formula-fed infants with an established , mixed-type microbiota in the weaning period", "This article by the ESPGHAN Committee on Nutrition summarizes available information on the effects of adding prebiotic oligosaccharides to infant and follow-on formulae . Currently there are only limited studies evaluating prebiotic substances in dietetic products for infants . Although administration of prebiotic oligosaccharides has the potential to increase the total number of bifidobacteria in feces and may also soften stools , there is no published evidence of clinical benefits of adding prebiotic oligosaccharides to dietetic products for infants . Data on oligosaccharide mixtures in infant formulae do not demonstrate adverse effects , but further evaluation is recommended . Combinations and dosages in addition to those so far studied need to be fully evaluated with respect to both safety and efficacy before their use in commercial infant food products . Well- design ed and carefully conducted r and omized controlled trials with relevant inclusion /exclusion criteria , adequate sample sizes and vali date d clinical outcome measures are needed both in preterm and term infants . Future trials should define optimal quantity and types of oligosaccharides with prebiotic function , optimal dosages and duration of intake , short and long term benefits and safety . At the present time , therefore , the Committee takes the view that no general recommendation on the use of oligosaccharide supplementation in infancy as a prophylactic or therapeutic measure can be made", "This double-blind , r and omized , placebo-controlled study , aim ed to explore the effect of an infant milk formula ( IMF ) with 6 g/l short-chain galacto- and long-chain fructo-oligosaccharides ( scGOS/lcFOS , ratio 9:1 ) on basal immune parameters in 215 healthy , term infants during the first 26 wk of life . After birth , the infants received breast milk or were r and omized to receive an IMF with or without scGOS/lcFOS . Blood sample s were collected at the age of 8 wk and 26 wk for the analysis of serum immunoglobulins , lymphocyte sub population s , and cytokines . The scGOS/lcFOS group and the control group were compared in the statistical analysis . A breast fed group was included as a reference . In total , 187 Infants completed the study . No significant differences were observed between both formula groups in the different studied immune parameters at weeks 8 and 26 . This explorative study indicates that supplementation of infant formula with a mixture of prebiotic oligosaccharides did not change the basal level of the measured parameters of the developing immune system in healthy infants with a balanced immune system during the first 6 months of life in comparison to feeding a st and ard infant formula and in comparison to exclusive breastfeeding", "BACKGROUND Very-low-birth-weight ( VLBW ) infants are susceptible to glutamine depletion . Glutamine depletion has negative effects on intestinal integrity . The lower infection rate in VLBW infants receiving glutamine-enriched enteral nutrition may originate from improved intestinal integrity , as reflected by decreased intestinal permeability . The aim of our study was to investigate whether glutamine-enriched enteral nutrition in VLBW infants enhances the normal decrease in intestinal permeability , as measured by the sugar absorption test ( SAT ) . METHODS In a double-blind , r and omized , placebo-controlled trial , VLBW infants ( gestational age received enteral glutamine supplementation ( 0.3 g/kg/d ) or an isonitrogenous placebo supplementation ( alanine ) between days 3 and 30 of life . Intestinal permeability , determined from the urinary lactulose/mannitol ( L/M ) ratio after an oral dose of lactulose and mannitol , was assessed at 4 time points : before the start of the study , and at days 7 , 14 , and 30 of life . RESULTS At least 2 SATs were performed in 45/52 ( 86 % ) and 45/50 ( 90 % ) infants in the glutamine-supplemented and control groups , respectively . Baseline patient and nutrition characteristics were not different between the groups . There was no effect of glutamine-enriched enteral nutrition on the decrease of the L/M ratio between the start and end of the study ( p = .78 ) . In both treatment groups , median urinary lactulose concentrations decreased ( p median urinary mannitol concentrations increased ( p = .003 ) . CONCLUSIONS Glutamine-enriched enteral nutrition does not enhance the postnatal decrease in intestinal permeability in VLBW infants . Any beneficial effect of glutamine may involve other aspects of intestinal integrity ; for example , modulation of the intestinal inflammatory response", "The aim of this double-blind , r and omized , placebo-controlled study was to evaluate the effect of a prebiotic mixture on gastric motility in preterm newborns . After a feeding period of 15 days , gastric electrical activity was measured by electrogastrography , and the gastric emptying time was studied by ultrasound technique . No difference was seen in the daily increase of body weight , and no adverse events have been reported . The percentage of time in which propagation was detected in the electrogastrography signal was twice in newborns receiving formula with prebiotics with respect to placebo , and the gastric half-emptying time was 30 % faster in the prebiotic group than the placebo group . Prebiotic oligosaccharides can modulate the electrical activity and the gastric emptying and may improve the intestinal tolerance of enteral feeding in preterm infants", "A double‐blind , r and omized , controlled study was performed in 90 full term infants to evaluate dose‐related bifidogenic effects of a new synergistic mixture of galacto‐oligosaccharides ( GOS ) and fructo‐oligosacharides ( FOS ) . The GOS/FOS mixture showed a dose‐dependent stimulatory effect on the intestinal growth of bifidobacteria . Also stool consistency and faecal pH were positively affected", "Objectives : The present study was design ed to evaluate the effect of 2 different combinations of prebiotic ingredients , polydextrose ( PDX ) , galactooligosaccharides ( GOS ) , and lactulose ( LOS ) , at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age . Patients and Methods : Healthy , formula-fed , term infants ( n = 226 ) were r and omly assigned to 1 of 3 study formula groups : control group ( n = 76 ) , PG4 group ( control formula supplemented with 4 g/L of a prebiotic blend , n = 74 ) , or PGL8 group ( control formula supplemented with 8 g/L of a prebiotic blend , n = 76 ) . Anthropometric measurements were taken at 14 , 30 , 60 , 90 , and 120 days of age , and 24-hour dietary recall and 24-hour tolerance recall were recorded at 30 , 60 , 90 , and 120 days of age . Adverse events were recorded throughout the study . Results : There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point . Significant differences in stool consistency were detected among the 3 formula groups at 30 , 60 , and 90 days of age ( P looser stools than the control group . The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age ( P = 0.021 and P = 0.017 , respectively ) , but all of the groups were similar at 60 , 90 , and 120 days of age . A statistical difference was detected among the formula groups in 3 categories of adverse events : diarrhea ( control vs PG4 , 4 % vs 18 % , P = 0.008 ) , eczema ( PG4 vs control , 18 % vs 7 % , P = 0.046 ; PG4 vs PGL8 , 18 % vs 4 % , P = 0.008 ) , and irritability ( control vs PGL8 , 4 % vs 16 % , P = 0.027 ) . Conclusions : Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula . A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics", "Among other components of human milk , oligosaccharides might contribute to the high efficiency of calcium absorption of breastfed infants . In adults , it can be shown that dietary oligosaccharides can improve calcium absorption . The present analysis was performed to evaluate a possible influence of dietary oligosaccharides on parameters of calcium metabolism in preterm infants . The concentrations of calcium and phosphorus in plasma and in spot urine sample s as well as the plasma activity of the alkaline phosphatase were measured in preterm infants fed either a st and ard formula ( n= 15 ) or a formula supplemented with dietary oligosaccharides ( n= 15 ) at the end of a 4‐wk feeding period", "Background : Probiotic , prebiotic , and synbiotic ( a combination of pro- and prebiotic ) supplements increasingly are being used to prevent and treat a variety of health conditions . Although colonization is considered a key element in the success of such treatments , few clinical studies have addressed colonizing ability . Studies are even more limited in neonates and infants , who may benefit most from such treatment . The present study was conducted to determine the colonizing ability , tolerance , and impact on the stool flora of 7 days of administration of a synbiotic supplement to a neonatal cohort , in preparation for a larger hospital-based trial . Patients and Methods : In this r and omized , double-masked , controlled trial , healthy inborn newborns > 35 weeks of gestational age and > 1800 g birth weight were r and omized between 1 and 3 days after birth to receive an oral synbiotic preparation ( Lactobacillus plantarum and fructooligosaccharides ) or a dextrose saline placebo . Two babies were treated with the synbiotic preparation for every 1 baby treated with the placebo . Duration of therapy was 7 days . Comprehensive stool cultures were done at baseline and on days 3 , 7 , 14 , 21 , and 28 . Results : Nineteen infants received the active study supplement and 12 infants received the placebo for 7 days . L plantarum was cultured from the stools of 84 % of the treated infants after 3 days of treatment , and from 95 % of infants on day 28 after birth . Of the infants , 100 % , 94 % , 88 % , 56 % , and 32 % remained colonized at months 2 , 3 , 4 , 5 , and 6 , respectively . In both groups , the total mean number of species and the mean log colony counts increased over time . The number of bacterial species was significantly higher on days 21 and 28 in the synbiotic preparation group compared with placebo ( P = 0.002 and 0.03 , respectively ) . There was a linear increase in the mean log gram-negative colony counts in the placebo group during the 4-week period that was significantly higher than that in the Lactobacillus group on days 14 , 21 , and 28 ( P higher gram-positive colony counts on days 14 ( P = 0.002 ) and 28 ( P = 0.04 ) . Only 1 infant in the placebo group was colonized with L fermentum during the first 28 days of life . No difference was found in the percent increase in weight between baseline and day 7 , but on day 28 and months 2 , 3 , and 6 , the percent increase from baseline was higher in the probiotic-treated group ( P ≤ 0.05 ) . The supplement was tolerated well . Conclusions : The synbiotic preparation colonized quickly after 3 days of administration and the infants stayed colonized for several months after therapy was stopped . There was an increase in bacterial diversity and gram-positive organisms and a reduction of gram-negative bacterial load in the treatment group . Because a combination preparation was used , it is difficult to specifically attribute the colonization to either the probiotic or prebiotic component in this study . Larger efficacy trials are warranted to examine the mechanism of action and precise effects of these supplements", "Secretory immunoglobulin A ( SIgA ) plays an important role in the defence of the gastrointestinal tract . The level of faecal SIgA antibody is associated with increased neutralization and clearance of viruses . Formula-fed infants who lack the transfer of protective maternal SIgA from breast milk may benefit from strategies to support maturation of humoral immunity and endogenous production of SIgA. We aim ed at study ing the effects of st and ard , prebiotic and probiotic infant formulas on the faecal SIgA levels . At birth , infants of whom the mother had decided not to breastfeed were allocated to one of three formula groups in a r and omized , double-blind fashion . Nineteen infants received st and ard infant formula ; 19 received prebiotic formula containing a specific mixture of 0.6 g galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and 19 received probiotic formula containing 6.0 x 10(9 ) cfu Bifidobacterium animalis/100 ml formula . Faecal sample s were taken on postnatal day 5 , day 10 , wk 4 and every 4 wk thereafter until wk 32 . SIgA in faeces was determined by an enzyme-linked immunosorbent assay . During the intervention , infants fed on prebiotic formula showed a trend towards higher faecal SIgA levels compared with the st and ard formula-fed infants reaching statistical significance at the age of 16 wk . In contrast , infants fed on the probiotic formula showed a highly variable faecal SIgA concentration with no statistically significant differences compared with the st and ard formula group . Formula-fed infants may benefit from infant formulas containing a prebiotic mixture of GOS and FOS because of the observed clear tendency to increase faecal SIgA secretion . Adding viable B. animalis strain Bb-12 to infant formula did not reveal any sign for such a trend", "Objective : To compare the effect of 2 prebiotic/probiotic products on weight gain , stool microbiota , and stool short-chain fatty acid ( SCFA ) content of premature infants . Patients and Methods : This r and omized , blinded , placebo-controlled trial included 90 premature infants treated with either a dietary supplement containing 2 lactobacillus species plus fructooligosaccharides ( CUL , Culturelle , ConAgra , Omaha , NE ) , a supplement containing several species of lactobacilli and bifidobacteria plus fructooligosaccharides ( PBP , ProBioPlus DDS , UAS Laboratories , Eden Prairie , MN ) , or placebo ( a dilute preparation of Pregestamil formula ) twice daily for 28 days or until discharge if earlier . The primary outcome was weight gain . Secondary outcomes were stool bacterial analysis by culture and 16S rDNA quantitative polymerase chain reaction and stool SCFA content measured by high performance liquid chromatography . Results : Both prebiotic/probiotic combinations contained more bacterial species than noted on the label . No significant effect on infant growth of either prebiotic/probiotic supplement was observed . By cultures , 64 % of infants receiving PBP became colonized with bifidobacteria , compared with 18 % of infants receiving CUL and 27 % of infants receiving placebo ( chi-square , P = 0.064 ) . No differences were noted between groups in colonization rates for lactobacilli , Gram-negative enteric bacteria , or staphylococci . By 16S rDNA polymerase chain reaction analysis , the bifidobacteria content in the stools of the infants receiving PBP was higher than in the infants receiving CUL or placebo ( Kruskal-Wallis , P = 0.011 ) . No significant differences in stool SCFA content were detected between groups . No adverse reactions were noted . Conclusions : Infants receiving PBP were more likely to become colonized with bifidobacteria . No significant differences in weight gain or stool SCFA content were detected", "Objective : To test the safety and effect on faecal microbiota of a formula with prebiotic oligosaccharides alone or in combination with acidic oligosaccharides in infants at the age of partial formula feeding . Patients and Methods : The study was a double-blind , placebo-controlled , r and omised intervention trial in which 82 healthy , full-term , partially breast-fed children , from 1 week to 3 months old , were given 1 of the following formulae : whey-based formula ( control group ) , whey-based formula with galacto- and long-chain fructo-oligosaccharides ( scGOS/lcFOS group ) , or whey-based formula with galacto- and long-chain fructo-oligosaccharides added with pectin-derived acidic oligosaccharides ( scGOS/lcFOS/pAOS group ) . Children were studied for the duration of the partial formula feeding period and every 2 weeks for 2 months after breast-feeding cessation . The total bacteria count and the proportion of 7 bacterial families were determined using in situ hybridisation coupled to flow cytometry . Results : The total bacterial count did not alter with time or type of feeding ( 9.9 ± 0.1 log10 cells per gram wet weight ) . Compared with the control group , there was an increase of the Bifidobacterium genus ( P = 0.0001 ) , and a decrease of proportions for the Bacteroides group ( P = 0.02 ) and the Clostridium coccoides group ( P = 0.01 ) in both oligosaccharide groups . The proportion of bifidobacteria was significantly higher in the scGOS/lcFOS/pAOS compared with the scGOS/lcFOS group ( P < 0.01 ) . Conclusions : Infant formulae appear to be clinical ly safe and effective on infant microbiota . They minimize the alteration of faecal microbiota after cessation of breast-feeding and promote bifidobacteria proportions , with a stronger effect when acidic oligosaccharides are present", "Objective : Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression . Very low birth weight ( VLBW ) infants are susceptible to glutamine depletion , as enteral nutrition is limited in the first weeks of life . Enteral glutamine supplementation may have a positive effect on feeding tolerance , infectious morbidity and short-term outcome . The aim of the study was to determine the effect of enteral glutamine supplementation on plasma amino acid concentrations , reflecting one aspect of safety of enteral glutamine supplementation in VLBW infants . Methods : In a double-blind placebo-controlled r and omized controlled trial , VLBW infants ( gestational age received enteral glutamine supplementation ( 0.3 g/kg per day ) or isonitrogenous placebo supplementation ( alanine ) between day 3 and day 30 of life . Supplementation was added to breast milk or to preterm formula . Plasma amino acid concentrations were measured at four time points : before the start of the study and at days 7 , 14 and 30 of life . Results : Baseline patient and nutritional characteristics were not different in glutamine ( n = 52 ) and control ( n = 50 ) groups . Plasma concentrations of most essential and non-essential amino acids increased throughout the study period . There was no effect of enteral glutamine supplementation . In particular , the increase of plasma glutamine and glutamate concentrations was not different between the treatment groups ( P = 0.49 and P = 0.34 respectively , day 30 ) . Conclusions : Enteral glutamine supplementation in VLBW infants does not alter plasma concentrations of glutamine , glutamate or other amino acids . Enteral supplementation in a dose of 0.3 g/kg per day seems safe in VLBW infants", "OBJECTIVE . Live probiotic bacteria and dietary prebiotic oligosaccharides ( together termed synbiotics ) increasingly are being used in infancy , but evidence of long-term safety is lacking . In a r and omized , placebo-controlled , double-blind trial , we studied the safety and long-term effects of feeding synbiotics to newborn infants . METHODS . Between November 2000 and March 2003 , pregnant mothers carrying infants at high risk for allergy were r and omly assigned to receive a mixture of 4 probiotic species ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve Bb99 , and Propionibacterium freudenreichii ssp shermanii ) or a placebo for 4 weeks before delivery . Their infants received the same probiotics with 0.8 g of galactooligosaccharides , or a placebo , daily for 6 months after birth . Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3 , 6 , and 24 months and from question naires at ages 3 , 6 , 12 , and 24 months . Growth data were collected at each time point . RESULTS . Of the 1018 eligible infants , 925 completed the 2-year follow-up assessment . Infants in both groups grew normally . We observed no difference in neonatal morbidity , feeding-related behaviors ( such as infantile colic ) , or serious adverse events between the study groups . During the 6-month intervention , antibiotics were prescribed less often in the synbiotic group than in the placebo group ( 23 % vs 28 % ) . Throughout the follow-up period , respiratory infections occurred less frequently in the synbiotic group ( geometric mean : 3.7 vs 4.2 infections ) . CONCLUSION . Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life", "BACKGROUND & AIMS In a previous study , we have found that glutamine supplementation decreased the infection rate in very low birth weight ( VLBW ) infants . In this study , we investigated whether this beneficial effect originated from increased number of bifidobacteria and lactobacilli in the intestinal microflora of these infants . METHODS In a r and omized controlled trial , VLBW infants ( gestational age received enteral glutamine supplementation ( 0.3g/kg/day ) or isonitrogenous placebo supplementation between d3 and d30 of life . Faecal microflora was determined by fluorescent in situ hybridization 43/52 ( glutamine group ) and 43/50 ( control group ) infants , > or = 2 sample s were analyzed . Baseline characteristics were not different between groups . The prevalence of bifidobacteria , lactobacilli , Escheria coIi , streptococci and clostridia was not different between groups ( p>0.05 ) . In both groups , colonization with bifidobacteria was delayed , whereas potentially pathogenic bacteria such as E. coli , appeared rapidly after birth . Antibiotic treatment decreased the prevalence of all faecal bacteria ( p infectious morbidity in VLBW infants that received glutamine supplementation was not associated with alterations in the prevalence of bifidobacteria , lactobacilli , E. coIi , streptococci and clostridia . In general , colonization with health-promoting bacteria was delayed , whereas potentially pathogenic bacteria appeared rapidly after birth . Antibiotic treatment delayed the bacterial colonization", "STUDY OBJECTIVES We sought to identify early life factors ( ie , first 4 years ) associated with wheeze , asthma , and bronchial hyperresponsiveness ( BHR ) at age 10 years , comparing their relative influence for these conditions . METHODS Children were seen at birth , and at 1 , 2 , 4 , and 10 years of age in a whole- population birth cohort study ( 1,456 subjects ) . Information was collected prospect ively on genetic and environmental risk factors . Skin-prick testing was performed at 4 years of age . Current wheeze ( in the last 12 months ) and currently diagnosed asthma ( CDA ) [ ie , current wheeze and ever-diagnosed asthmatic subject ] were recorded at 10 years of age when BHR was measured at bronchial challenge . Independent significant risk factors for these outcomes were identified by logistic regression . RESULTS Independent significance for current wheeze occurred with maternal asthma ( odds ratio [ OR ] , 2.08 ; 95 % confidence interval [ CI ] , 1.27 to 3.41 ) and paternal asthma ( OR , 2.12 ; 95 % CI 1.29 to 3.51 ) , recurrent chest infections at 2 years ( OR , 3.98 ; 95 % CI , 2.36 to 6.70 ) , atopy at 4 years of age ( OR , 3.69 ; 95 % CI , 2.36 to 5.76 ) , eczema at 4 years of age ( OR , 2.15 ; 95 % CI , 1.24 to 3.73 ) , and parental smoking at 4 years of age ( OR , 2.18 ; 95 % CI , 1.25 to 3.81 ) . For CDA , significant factors were maternal asthma ( OR , 2.26 ; 95 % CI , 1.24 to 3.73 ) , paternal asthma ( OR , 2.30 ; 95 % CI , 1.17 to 4.52 ) , and sibling asthma ( OR , 2.00 ; 95 % CI , 1.16 to 3.43 ) , recurrent chest infections at 1 year of age ( OR , 2.67 ; 95 % CI , 1.12 to 6.40 ) and 2 years of age ( OR , 4.11 ; 95 % CI , 2.06 to 8.18 ) , atopy at 4 years of age ( OR , 7.22 ; 95 % CI , 4.13 to 12.62 ) , parental smoking at 1 year of age ( OR , 1.99 ; 95 % CI , 1.15 to 3.45 ) , and male gender ( OR , 1.72 ; 95 % CI , 1.01 to 2.95 ) . For BHR , atopy at 4 years of age ( OR , 5.38 ; 95 % CI , 3.06 to 9.47 ) and high social class at birth ( OR , 2.03 ; 95 % CI , 1.16 to 3.53 ) proved to be significant . CONCLUSIONS Asthmatic heredity , predisposition to early life atopy , plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age . BHR at 10 years of age has a narrower risk profile , suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR", "OBJECTIVE To assess the safety and prebiotic effects of lactulose in preterm infants . STUDY DESIGN This was a prospect i ve , double-blinded , placebo-controlled , single-center study in 23- to 34-weeks premature infants . The study group received 1 % lactulose , and control infants received 1 % dextrose in all feeds ( human milk or formula ) . RESULTS Twenty-eight infants participated ( 15 lactulose , 13 placebo ) . Small doses of lactulose appeared to be safe and did not cause diarrhea . Premature infants on lactulose had more Lactobacilli-positive stool cultures that appeared earlier with larger number of colonies . The lactulose group tended to have less intolerance to enteral feedings , to reach full oral feeds earlier , and to be discharged home earlier . They also tended to have fewer episodes of late-onset sepsis , lower Bell stage necrotizing enterocolitis , and their nutritional laboratory indices were better , especially calcium and total protein . CONCLUSIONS This pilot study supports the safety of supplementing preterm infants ' feeds with low doses of lactulose . It also demonstrated trends that may suggest positive prebiotic effects", "OBJECTIVE Cholesterol is a nutrient of essential importance in infant feeding because it is necessary in membrane development . In adults with high lipid levels , high doses of inulin ( oligofructose ) inconsistently decreased levels of serum cholesterol . The aim of the present study was to evaluate cholesterol and triacylglycerol levels in infants receiving a formula with a specific mixture of 0.6 g/100 mL of galacto-oligosaccharides ( GOS ) and long-chain fructo-oligosaccharides ( lcFOS ) in a ratio of 9/1 , a control formula , or breast milk . Because the level of lcFOS in the infant milk is low , we hypothesized that there would be no differences between the formula groups . METHODS Two hundred fifteen infants were included in a prospect i ve , r and omized , double-blinded , placebo-controlled trial during the first 6 mo of life . Formula-fed infants were r and omized to receive a st and ard infant formula with a specific mixture of 0.6 g/100 mL of GOS/lcFOS , in a ratio of 9/1 , or a control formula . Breast-fed infants were r and omized to receive one of these two formulas after the mother had decided to discontinue breastfeeding . Serum levels of cholesterol , high-density lipoprotein , low-density lipoprotein ( LDL ) , and triacylglycerol were determined at 8 and 26 wk of age and were provided for infants who received the GOS/lcFOS formula or control formula from birth or after cessation of breastfeeding and for the subgroups that were fully fed with breast milk and formula . RESULTS One hundred eighty-seven infants completed the study . Total cholesterol and LDL levels at 8 and 26 wk were significantly lower in the formula-fed groups than in the breast-fed infants . There were no significant differences between the formula-fed groups . Levels of triacylglycerols and high-density lipoprotein did not differ between groups . CONCLUSION Our study demonstrated no differences in total cholesterol and LDL cholesterol in infants receiving an infant formula with GOS/lcFOS from infants receiving a control infant formula . Furthermore , total cholesterol and LDL cholesterol levels were higher in breast-fed infants than in formula-fed infants", "BACKGROUND The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system . Probiotics , live health-promoting microbes , might offer such stimulation . OBJECTIVE We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases . METHODS We r and omized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery . Their infants received the same probiotics plus galacto-oligosaccharides ( n = 461 ) or a placebo ( n = 464 ) for 6 months . At 2 years , we evaluated the cumulative incidence of allergic diseases ( food allergy , eczema , asthma , and allergic rhinitis ) and IgE sensitization ( positive skin prick test response or serum antigen-specific IgE level > 0.7 kU/L ) . Fecal bacteria were analyzed during treatment and at age 2 years . RESULTS Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated ( atopic ) diseases ( odds ratio [ OR ] , 0.71 ; 95 % CI , 0.50 - 1.00 ; P = .052 ) . Probiotic treatment reduced eczema ( OR , 0.74 ; 95 % CI , 0.55 - 0.98 ; P = .035 ) and atopic eczema ( OR , 0.66 ; 95 % CI , 0.46 - 0.95 ; P = .025 ) . Lactobacilli and bifidobacteria more frequently ( P treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema . The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics . CLINICAL IMPLICATION S The prevention of atopic eczema in high-risk infants is possible by modulating the infant 's gut microbiota with probiotics and prebiotics", "BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit . Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children" ]	41183132-06ff-11f0-808a-c43d1ab1c353
Interventions using the " Four Immeasurables Meditations " ( FIM ) are effective for various outcomes ; however , whether increased meditation practice in these interventions leads to better results has not been well investigated . This systematic review included 22 FIM interventions that reported associations between the amount of meditation practice and its outcomes . Despite the heterogeneity in intervention components and outcome variables , there were generally few significant associations between amount of meditation practice and its outcomes . Specifically , only five studies reported that more than half of the calculated results were significant . In comparison with correlations between total amount of practice and overall outcomes , the short-term influence of meditation practice was evaluated in fewer studies ; however , it had a better association with outcomes . More studies are required that address the underlying mechanisms that eluci date how meditation practice leads to outcome changes in daily life . In this study , two promising mechanisms with initial evidence were discussed . This review also summarized common method ological issues including a lack of experimental manipulation and inaccurate measuring of meditation practice	[ "OBJECTIVES The aim of these two studies was to evaluate the effectiveness of the Mindful Self-Compassion ( MSC ) program , an 8-week workshop design ed to train people to be more self-compassionate . METHODS Study 1 was a pilot study that examined change scores in self-compassion , mindfulness , and various wellbeing outcomes among community adults ( N = 21 ; mean [ M ] age = 51.26 , 95 % female ) . Study 2 was a r and omized controlled trial that compared a treatment group ( N = 25 ; M age = 51.21 ; 78 % female ) with a waitlist control group ( N = 27 ; M age = 49.11 ; 82 % female ) . RESULTS Study 1 found significant pre/post gains in self-compassion , mindfulness , and various wellbeing outcomes . Study 2 found that compared with the control group , intervention participants reported significantly larger increases in self-compassion , mindfulness , and wellbeing . Gains were maintained at 6-month and 1-year follow-ups . CONCLUSIONS The MSC program appears to be effective at enhancing self-compassion , mindfulness , and wellbeing", "The ability to accurately infer others ' mental states from facial expressions is important for optimal social functioning and is fundamentally impaired in social cognitive disorders such as autism . While pharmacologic interventions have shown promise for enhancing empathic accuracy , little is known about the effects of behavioral interventions on empathic accuracy and related brain activity . This study employed a r and omized , controlled and longitudinal design to investigate the effect of a secularized analytical compassion meditation program , cognitive-based compassion training ( CBCT ) , on empathic accuracy . Twenty-one healthy participants received functional MRI scans while completing an empathic accuracy task , the Reading the Mind in the Eyes Test ( RMET ) , both prior to and after completion of either CBCT or a health discussion control group . Upon completion of the study interventions , participants r and omized to CBCT and were significantly more likely than control subjects to have increased scores on the RMET and increased neural activity in the inferior frontal gyrus ( IFG ) and dorsomedial prefrontal cortex ( dmPFC ) . Moreover , changes in dmPFC and IFG activity from baseline to the post-intervention assessment were associated with changes in empathic accuracy . These findings suggest that CBCT may hold promise as a behavioral intervention for enhancing empathic accuracy and the neurobiology supporting it", "B. L. Fredrickson 's ( 1998 , 2001 ) broaden- and -build theory of positive emotions asserts that people 's daily experiences of positive emotions compound over time to build a variety of consequential personal re sources . The authors tested this build hypothesis in a field experiment with working adults ( n = 139 ) , half of whom were r and omly-assigned to begin a practice of loving-kindness meditation . Results showed that this meditation practice produced increases over time in daily experiences of positive emotions , which , in turn , produced increases in a wide range of personal re sources ( e.g. , increased mindfulness , purpose in life , social support , decreased illness symptoms ) . In turn , these increments in personal re sources predicted increased life satisfaction and reduced depressive symptoms . Discussion centers on how positive emotions are the mechanism of change for the type of mind-training practice studied here and how loving-kindness meditation is an intervention strategy that produces positive emotions in a way that outpaces the hedonic treadmill effect", "Meditation practice s may impact physiological pathways that are modulated by stress and relevant to disease . While much attention has been paid to meditation practice s that emphasize calming the mind , improving focused attention , or developing mindfulness , less is known about meditation practice s that foster compassion . Accordingly , the current study examined the effect of compassion meditation on innate immune , neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress reactivity . Sixty-one healthy adults were r and omized to 6 weeks of training in compassion meditation ( n=33 ) or participation in a health discussion control group ( n=28 ) followed by exposure to a st and ardized laboratory stressor ( Trier social stress test [ TSST ] ) . Physiologic and behavioral responses to the TSST were determined by repeated assessment s of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States ( POMS ) . No main effect of group assignment on TSST responses was found for IL-6 , cortisol or POMS scores . However , within the meditation group , increased meditation practice was correlated with decreased TSST-induced IL-6 ( r(p)=-0.46 , p=0.008 ) and POMS distress scores ( r(p)=-0.43 , p=0.014 ) . Moreover , individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median , who did not differ from controls . These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses , although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity", "Purpose This study assessed the feasibility of a meditation-based program called Cognitively-Based Compassion Training ( CBCT ) with breast cancer survivors . Enrollment and participant satisfaction with a novel intervention , adherence to program requirements , and differences between the intervention group and wait list controls on self-report measures were also assessed . Additionally , cortisol , a stress-related endocrine biomarker , was assessed . Methods Participants ( n = 33 ) were r and omly assigned to CBCT or the wait list . CBCT provided eight weekly , 2-h classes and a “ booster ” CBCT session 4 weeks later . CBCT participants were expected to attend classes and meditate between classes at least three times per week . Pre-/post-intervention and follow-up question naires measured symptom change ( depression , intrusive thoughts , perceived stress , fear of cancer recurrence , fatigue/vitality , loneliness , and quality of life ) . Saliva sample s were collected at the same periods to assess the slope of diurnal cortisol activity . Results Enrollment , class attendance , home practice time , and patient satisfaction exceeded expectations . Compared to controls , post-intervention , the CBCT group showed suggestions of significant improvements in depression , avoidance of intrusive thoughts , functional impairment associated with fear of recurrence , mindfulness , and vitality/fatigue . At follow-up , less perceived stress and higher mindfulness were also significant in the CBCT group . No significant changes were observed on any other measure including diurnal cortisol activity . Conclusions Within the limits of a pilot feasibility study , results suggest that CBCT is a feasible and highly satisfactory intervention potentially beneficial for the psychological well-being of breast cancer survivors . However , more comprehensive trials are needed to provide systematic evidence . Relevance CBCT may be very beneficial for improving depression and enhancing well-being during breast cancer survivorship", "BACKGROUND Children exposed to early life adversity ( ELA ) have been shown to have elevated circulating concentrations of inflammatory markers that persist into adulthood . Increased inflammation in individuals with ELA is believed to drive the elevated risk for medical and psychiatric illness in the same individuals . This study sought to determine whether Cognitively Based Compassion Training ( CBCT ) reduced C-reactive protein ( CRP ) in adolescents in foster care with high rates of ELA , and to evaluate the relationship between CBCT engagement and changes in CRP given prior evidence from our group for an effect of practice on inflammatory markers . It was hypothesized that increasing engagement would be associated with reduced CRP from baseline to the 6-week assessment . METHODS Seventy-one adolescents in the Georgia foster care system ( 31 females ) , aged 13 - 17 , were r and omized to either 6 weeks of CBCT or a wait-list condition . State records were used to obtain information about each participant 's history of trauma and neglect , as well as reason for placement in foster care . Saliva was collected before and again after 6 weeks of CBCT or the wait-list condition . Participants in the CBCT group completed practice diaries as a means of assessing engagement with the CBCT . RESULTS No difference between groups was observed in salivary CRP concentrations . Within the CBCT group , practice sessions during the study correlated with reduced CRP from baseline to the 6-week assessment . CONCLUSIONS Engagement with CBCT may positively impact inflammatory measures relevant to health in adolescents at high risk for poor adult functioning as a result of significant ELA , including individuals placed in foster care . Longer term follow-up will be required to evaluate if these changes are maintained and translate into improved health outcomes", "Purpose : Loving-kindness meditation has been used for centuries in the Buddhist tradition to develop love and transform anger into compassion . This pilot study tested an 8-week loving-kindness program for chronic low back pain patients . Method : Patients ( N = 43 ) were r and omly assigned to the intervention or st and ard care . St and ardized measures assessed patients ’ pain , anger , and psychological distress . Findings : Post and follow-up analyses showed significant improvements in pain and psychological distress in the loving-kindness group , but no changes in the usual care group . Multilevel analyses of daily data showed that more loving-kindness practice on a given day was related to lower pain that day and lower anger the next day . Conclusions : Preliminary results suggest that the loving-kindness program can be beneficial in reducing pain , anger , and psychological distress in patients with persistent low back pain . Implication s : Clinicians may find loving-kindness meditation helpful in the treatment of patients with persistent pain" ]	411831aa-06ff-11f0-808a-c43d1ab1c353
Background To investigate the use of physical activity monitors ( PAMs ) for the elderly , the scientific literature should be systematic ally review ed and the effect quantified , as the evidence seems inconclusive . Methods and design R and omized controlled trials and r and omized crossover trials , with participants with a mean age above 65 years , comparing any PAM intervention with other control interventions or no intervention , will be included . This protocol is detailed according to the recommendations of the Cochrane H and book , and it is reported according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol s statement . Results We will present results from the search in a flow diagram . The results from the analyses will include regular meta-analyses , stratified analyses , and meta-regressions . The results on each outcome of interest will be presented in a summary of findings table . Discussion This paper will explore and analyze the heterogeneity of the results and try to identify variables that will enhance the effect of PAMs in elderly . The results will be useful to research ers working with elderly and /or PAMs , health care professionals working with elderly , and relatives together with the elderly themselves . Systematic review registration PROSPERO CRD42018083648	[ "Rationale : Increasing physical activity is a key therapeutic aim in chronic obstructive pulmonary disease ( COPD ) . Pulmonary rehabilitation ( PR ) improves exercise capacity , but there is conflicting evidence regarding its ability to improve physical activity levels . Objectives : To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate‐intensity physical activity ( time expending ≥3 metabolic equivalents [ METs ] ) by people with COPD . Methods : In this single‐blind r and omized controlled trial , participants were assigned 1:1 to receive a control intervention ( PR comprising 8 wk , two supervised sessions per week ) or the trial intervention ( PR plus pedometer‐directed step targets , review ed weekly for 8 wk ) . In the r and omization process , we used minimization to balance groups for age , sex , FEV1 percent predicted , and baseline exercise capacity and physical activity levels . Outcome assessors and PR therapists were blinded to group allocation . The primary analysis was based on the intention‐to‐treat principle . Measurements and Main Results : The primary outcome was change from baseline to 8 weeks in accelerometer‐measured daily time expending at least 3 METs . A total of 152 participants ( 72 % male ; mean [ SD ] FEV1 percent predicted , 50.5 % [ 21.2 ] ; median [ first quartile , third quartile ] time expending ≥3 METs , 46 [ 21 , 92 ] min ) were enrolled and assigned to the intervention ( n = 76 ) or control ( n = 76 ) arm . There was no significant difference in change in time expending at least 3 METs between the intervention and control groups at 8 weeks ( median [ first quartile , third quartile ] difference , 0.5 [ −1.0 , 31.0 ] min ; P = 0.87 ) or at the 6‐month follow‐up ( 7.0 [ −9 , 27 ] min ; P = 0.16 ) . Conclusions : Pedometer‐directed step‐count targets during an outpatient PR program did not enhance moderate‐intensity physical activity levels in people with COPD . Clinical trial registered with www . clinical trials.gov ( NCT01719822 )", "Background Physical activity contributes to older adults ’ autonomy , mobility , and quality of life as they age , yet fewer than 1 in 5 engage in activities as recommended . Many older adults track their exercise using pencil and paper , or their memory . Commercially available physical activity monitors ( PAM ) have the potential to facilitate these tracking practice s and , in turn , physical activity . An assessment of older adults ’ long-term experiences with PAM is needed to underst and this potential . Objective To assess short and long-term experiences of adults > 70 years old using a PAM ( Fitbit One ) in terms of acceptance , ease-of-use , and usefulness : domains in the technology acceptance model . Methods This prospect i ve study included 95 community-dwelling older adults , all of whom received a PAM as part of r and omized controlled trial piloting a fall-reducing physical activity promotion intervention . Ten-item surveys were administered 10 weeks and 8 months after the study started . Survey ratings are described and analyzed over time , and compared by sex , education , and age . Results Participants were mostly women ( 71/95 , 75 % ) , 70 to 96 years old , and had some college education ( 68/95 , 72 % ) . Most participants ( 86/95 , 91 % ) agreed or strongly agreed that the PAM was easy to use , useful , and acceptable both 10 weeks and 8 months after enrolling in the study . Ratings dropped between these time points in all survey domains : ease-of-use ( median difference 0.66 points , P=.001 ) ; usefulness ( median difference 0.16 points , P=.193 ) ; and acceptance ( median difference 0.17 points , P=.032 ) . Differences in ratings by sex or educational attainment were not statistically significant at either time point . Most participants 80 + years of age ( 28/37 , 76 % ) agreed or strongly agreed with survey items at long-term follow-up , however their ratings were significantly lower than participants in younger age groups at both time points . Conclusions Study results indicate it is feasible for older adults ( 70 - 90 + years of age ) to use PAMs when self-tracking their physical activity , and provide a basis for developing recommendations to integrate PAMs into promotional efforts . Trial Registration Clinical trials.gov NCT02433249 ; https:// clinical trials.gov/ct2/show/NCT02433249 ( Archived by WebCite at http://www.webcitation.org/6gED6eh0I", "Background Walking can improve functional status , and a pedometer and goal setting can increase walking and , potentially , gait speed . The efficacy of pedometer use and goal setting for increasing step counts among overweight and obese adults with multiple comorbid conditions has not been evaluated . Methods We recruited and r and omly assigned obese or overweight adults with multimorbidity to immediate pedometer use with goal setting or delayed pedometer use , using a crossover design . The primary outcome of interest was step count , with secondary outcomes of gait speed and grip strength , with comparison between the intervention and delayed pedometer groups . Results Mean ( st and ard deviation [ SD ] ) age of the 130 participants was 63.4 ( 15.0 ) years . At 2 months , mean ( SD ) steps for the immediate pedometer use group ( n=64 ) was 5,337 ( 3,096 ) , compared with 4,446 ( 2,422 ) steps in the delayed pedometer group ( n=66 ) ( P=0.08 ) . Within-group step count increased nonsignificantly , by 179 steps in the immediate pedometer group and 212 steps in the delayed pedometer group after 2 months of intervention , with no significant difference between the groups . Gait speed significantly increased by 0.08 m/s ( P grip strength significantly increased by 1.6 kg ( P pedometer group . Conclusion Pedometer use and goal setting did not significantly increase step count among overweight and obese adults with multimorbidity . The absolute step count was lower than many reported averages . Gait speed and grip strength increased with immediate pedometer use . The use of pedometers and goal setting may have an attenuated response in this population", "Background Brisk walking in older people can increase step-counts and moderate to vigorous intensity physical activity ( MVPA ) in ≥10-minute bouts , as advised in World Health Organization guidelines . Previous interventions have reported step-count increases , but not change in objective ly measured MVPA in older people . We assessed whether a primary care nurse-delivered complex intervention increased objective ly measured step-counts and MVPA . Methods and Findings A total of 988 60–75 year olds , able to increase walking and r and omly selected from three UK family practice s , were invited to participate in a parallel two-arm cluster r and omised trial ; r and omisation was by household . Two-hundred-ninety-eight people from 250 households were r and omised between 2011 and 2012 ; 150 individuals to the intervention group , 148 to the usual care control group . Intervention participants received four primary care nurse physical activity ( PA ) consultations over 3 months , incorporating behaviour change techniques , pedometer step-count and accelerometer PA intensity feedback , and an individual PA diary and plan . Assessors were not blinded to group status , but statistical analyses were conducted blind . The primary outcome was change in accelerometry assessed average daily step-counts between baseline and 3 months , with change at 12 months a secondary outcome . Other secondary outcomes were change from baseline in time in MVPA weekly in ≥10-minute bouts , accelerometer counts , and counts/minute at 3 months and 12 months . Other outcomes were adverse events , anthropometric measures , mood , and pain . Qualitative evaluations of intervention participants and practice nurses assessed the intervention ’s acceptability . At 3 months , eight participants had withdrawn or were lost to follow-up , 280 ( 94 % ) individuals provided primary outcome data . At 3 months changes in both average daily step-counts and weekly MVPA in ≥10-minute bouts were significantly higher in the intervention than control group : by 1,037 ( 95 % CI 513–1,560 ) steps/day and 63 ( 95 % CI 40–87 ) minutes/week , respectively . At 12 months corresponding differences were 609 ( 95 % CI 104–1,115 ) steps/day and 40 ( 95 % CI 17–63 ) minutes/week . Counts and counts/minute showed similar effects to steps and MVPA . Adverse events , anthropometry , mood , and pain were similar in the two groups . Participants and practice nurses found the intervention acceptable and enjoyable . Conclusions The PACE-Lift trial increased both step-counts and objective ly measured MVPA in ≥10-minute bouts in 60–75 year olds at 3 and 12 months , with no effect on adverse events . To our knowledge , this is the first trial in this age group to demonstrate objective MVPA increases and highlights the value of individualised support incorporating objective PA assessment in a primary care setting . Trial Registration Controlled-Trials.com IS RCT", "BACKGROUND The health benefits of leisure-time physical activity are well known , but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear . We assessed the health benefits of a range of volumes of physical activity in a Taiwanese population . METHODS In this prospect i ve cohort study , 416,175 individuals ( 199,265 men and 216,910 women ) participated in a st and ard medical screening programme in Taiwan between 1996 and 2008 , with an average follow-up of 8·05 years ( SD 4·21 ) . On the basis of the amount of weekly exercise indicated in a self-administered question naire , participants were placed into one of five categories of exercise volumes : inactive , or low , medium , high , or very high activity . We calculated hazard ratios ( HR ) for mortality risks for every group compared with the inactive group , and calculated life expectancy for every group . FINDINGS Compared with individuals in the inactive group , those in the low-volume activity group , who exercised for an average of 92 min per week ( 95 % CI 71 - 112 ) or 15 min a day ( SD 1·8 ) , had a 14 % reduced risk of all-cause mortality ( 0·86 , 0·81 - 0·91 ) , and had a 3 year longer life expectancy . Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4 % ( 95 % CI 2·5 - 7·0 ) and all-cancer mortality by 1 % ( 0·3 - 4·5 ) . These benefits were applicable to all age groups and both sexes , and to those with cardiovascular disease risks . Individuals who were inactive had a 17 % ( HR 1·17 , 95 % CI 1·10 - 1·24 ) increased risk of mortality compared with individuals in the low-volume group . INTERPRETATION 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit , even for individuals at risk of cardiovascular disease . FUNDING Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes", "Background Low activity levels in inpatient rehabilitation are associated with adverse outcomes . The study aim ed to test whether activity levels can be increased by the provision of monitored activity data to patients and clinicians in the context of explicit goal setting . Methods A r and omized controlled trial in three sites in Australia included 255 in patients aged 60 and older who had a rehabilitation goal to become ambulant . The primary outcome was patients ’ walking time measured by accelerometers during the rehabilitation admission . Walking times from accelerometry were made available daily to treating therapists and intervention participants to motivate patients to improve incidental activity levels and reach set goals . For the control group , ‘ usual care ’ was followed , including the setting of mobility goals ; however , for this group , neither staff nor patients received data on walking times to aid the setting of daily walking time targets . Results The median daily walking time in the intervention group increased from 10.3 minutes at baseline to 32.1 minutes at day 28 , compared with an increase from 9.5 to 26.5 minutes per day in the control group . Subjects in the intervention group had significantly higher non-therapy walking time by about 7 minutes [ mean ( 95 % CI ) : 24.6 ( 21.7 , 27.4 ) ] compared to those in the control group [ mean(95 % CI ) : 17.3 ( 14.4 , 20.3 ) ] ( p = 0.001 ) . Conclusions Daily feedback to patients and therapists using an accelerometer increased walking times during rehabilitation admissions . The results of this study suggest objective monitoring of activity levels could provide clinicians with information on clinical ly important , mobility-related activities to assist goal setting . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611000034932", "OBJECTIVES To investigate whether a 12-week physical and cognitive exercise program can improve cognitive function and brain activation efficiency in community-dwelling older adults . DESIGN R and omized controlled trial . SETTING Kyoto , Japan . PARTICIPANTS Community-dwelling older adults ( N = 48 ) were r and omized into an exercise group ( n = 24 ) and a control group ( n = 24 ) . INTERVENTION Exercise group participants received a weekly dual task-based multimodal exercise class in combination with pedometer-based daily walking exercise during the 12-week intervention phase . Control group participants did not receive any intervention and were instructed to spend their time as usual during the intervention phase . MEASUREMENTS The outcome measures were global cognitive function , memory function , executive function , and brain activation ( measured using functional magnetic resonance imaging ) associated with visual short-term memory . RESULTS Exercise group participants had significantly greater postintervention improvement in memory and executive functions than the control group ( P activation was found in several brain regions associated with visual short-term memory , including the prefrontal cortex , in the exercise group ( P physical and cognitive exercise program can improve the efficiency of brain activation during cognitive tasks in older adults , which is associated with improvements in memory and executive function", "PURPOSE We evaluated the effects of low-intensity and home-based pulmonary rehabilitation ( PR ) on physical activity ( PA ) and the feedback provided by a pedometer in stable elderly patients with chronic obstructive pulmonary disease ( COPD ) . METHODS We assessed PA using a newly developed triaxial accelerometer ( A-MES ™ , Kumamoto , Japan ) , which measures the time spent walking , st and ing , sitting and lying down . Twenty-seven elderly patients with COPD ( age 74 ± 8 yrs ; % FEV1 56.6 ± 18.7 % ) participated . They were r and omly selected to undergo PR ( pulmonary rehabilitation only ) or PR + P ( PR plus the feedback from using a pedometer ) . Their PA and pulmonary function , exercise capacity ( 6-min walking distance ; 6MWD ) , quadriceps femoris muscle force ( QF ) were evaluated before the PR began ( baseline ) and at 1 year later . We compared the patients ' changes in PA and other factors between the baseline values and those obtained 1 year later and analyzed the relationships between the changes in PA and other factors in the both groups . RESULTS The increase in the time spent walking in the PR + P group ( 51.3 ± 63.7 min/day ) was significantly greater than that of PR group ( 12.3 ± 25.5 min/day ) after the PR . The improvement rate of daily walking time after PR was significantly correlated with that of the 6MWD and QF in all subjects . CONCLUSIONS These data suggest that low-intensity and home-based PR with the feedback from using pedometer was effective in improving PA , and the improvements of physiological factors were correlated with increased walking time in stable elderly patients with COPD", "This study investigated the effect of a 12-week pedometer-based intervention on daily step counts of 147 older adults r and omly assigned to an intervention or wait-list control group ( M age = 72.9 years , SD = 8.8 ) . The intervention group significantly increased their daily step counts after 12 weeks ( M = 639 , SD = 2,239 ) and continued to significantly increase during a 12-week maintenance period ( M = 680 , SD = 1,721 ) . The control group exhibited no change during the control period ( M = -393 , SD = 2,050 ) but had a significant increase in daily step counts ( M = 1,580 , SD = 2,305 ) when enrolled in the intervention . The pedometer-based intervention was effective in increasing participants ' daily step counts", "OBJECTIVES To determine the effectiveness of a behavior change intervention ( BCI ) with or without a pedometer in increasing physical activity in sedentary older women . DESIGN Prospect i ve r and omized controlled trial . SETTING Primary care , City of Dundee , Scotl and . PARTICIPANTS Two hundred four sedentary women aged 70 and older . INTERVENTIONS Six months of BCI , BCI plus pedometer ( pedometer plus ) , or usual care . MEASUREMENTS PRIMARY OUTCOME change in daily activity counts measured by accelerometry . SECONDARY OUTCOMES Short Physical Performance Battery , health-related quality of life , depression and anxiety , falls , and National Health Service re source use . RESULTS One hundred seventy-nine of 204 ( 88 % ) women completed the 6-month trial . Withdrawals were highest from the BCI group ( 15/68 ) followed by the pedometer plus group ( 8/68 ) and then the control group ( 2/64 ) . After adjustment for baseline differences , accelerometry counts increased significantly more in the BCI group at 3 months than in the control group ( P = .002 ) and the pedometer plus group ( P = .04 ) . By 6 months , accelerometry counts in both intervention groups had fallen to levels that were no longer statistically significantly different from baseline . There were no significant changes in the secondary outcomes . CONCLUSION The BCI was effective in objective ly increasing physical activity in sedentary older women . Provision of a pedometer yielded no additional benefit in physical activity , but may have motivated participants to remain in the trial" ]	41183222-06ff-11f0-808a-c43d1ab1c353
Disordered eating is elevated in bariatric surgery patients and is a risk factor for poor surgical outcomes . A systematic review evaluated the definitions and measurement methods used to identify and assess disordered eating in patients following bariatric surgery . One hundred articles were identified featuring 35 question naires and 23 interviews . There were numerous variations to diagnostic criteria and amendments to measures to account for the post-surgical eating context . Only 20 % of question naires and 4 % of interviews had reported psychometric evaluation in post-surgery sample s. Results highlight the need for a consistent definition of disordered eating and for current assessment measures to be ( a ) adapted to account for the altered gastrointestinal system in patients following surgery and ( b ) psychometrically evaluated in bariatric surgery patients	[ "The purpose of this study was to conduct an assessment of binge eating severity among obese persons . Two question naires were developed . A 16-item Binge Eating Scale was constructed describing both behavioral manifestations ( e.g. , eating large amounts of food ) and feeling/cognitions surrounding a binge episode ( e.g. , guilt , fear of being unable to stop eating ) . An 11-item Cognitive Factors Scale was developed measure two cognitive phenomena thought to be related to binge eating : the tendency to set unrealistic st and ards for a diet ( e.g. , eliminating \" favorite foods \" ) and low efficacy expectations for sustaining a diet . The results showed that the Binge Eating Scale successfully discriminated among persons judged by trained interviewers to have either no , moderate or severe binge eating problems . Significant correlation between the scales were obtained such that severe bingers tended to set up diets which were unrealistically strict while reporting low efficacy expectations to sustain a diet . The discussion highlighted the differences among obese persons on binge eating severity and emphasized the role of cognitions in the relapse of self control of eating", "OBJECTIVE To determine the prevalence of night-eating syndrome in the general population and among a new sample of obesity surgery patients . METHODS Night-eating syndrome was defined by presence of morning anorexia , excessive evening eating , evening tension and /or feeling upset , and insomnia . A r and omly selected sample of 2,097 adults ( survey sample ) answered structured interview questions on night-eating syndrome . A self-report form was completed by 111 patients who had received gastric restriction surgery for obesity at a patient reunion ( patient sample ) . RESULTS Prevalence of night-eating syndrome in the survey sample was 1.5 % ( 31 of 2,097 ) . Prevalence in the patient sample was 27 % ( 30 of 111 ) . Weights for subjects in each sample , with and without the syndrome , were comparable . DISCUSSION Prevalence of night-eating syndrome was higher in the patient sample than in the survey sample . Within each sample , presence of the syndrome was not related to weight . Prevalence in the survey sample was within the range reported for binge-eating disorder . Night-eating syndrome may warrant consideration as a distinct eating disorder", "BACKGROUND Gastric restrictive surgery induces a marked change in eating behavior . However , the relationship between preoperative and postoperative eating behavior and weight loss outcome has received limited attention . OBJECTIVE This study assessed a range of eating behaviors before and 1 year after laparoscopic adjustable gastric b and ing ( LAGB ) and explored the nature and extent of change in eating patterns , their clinical associates , and impact on weight loss . METHODS AND PROCEDURES A 12-month observational study assessed presurgical and postsurgical binge eating disorder ( BED ) , uncontrolled eating , night eating syndrome ( NES ) , grazing , nutrient intake and eating-related behaviors , and markers of psychological distress . A total of 129 subjects ( 26 male and 103 female , mean age 45.2 + /- 11.5 and BMI 44.3 + /- 6.8 ) participated in this study . RESULTS Presurgical BED , uncontrolled eating , and NES occurred in 14 % , 31 % , and 17.1 % of subjects , which reduced after surgery to 3.1 % , 22.5 % , and 7.8 % , respectively ( P = 0.05 for all ) . Grazing was prevalent before ( 26.3 % ) and after surgery ( 38.0 % ) . Preoperative BED most frequently became grazers ( P = 0.029 ) . The average percentage weight loss ( % WL ) was 20.8 + /- 8.5 % ; range -0.67 to 50.0 % and percentage of excess weight loss ( % EWL ) 50.0 + /- 20.7 % ; range -1.44 to 106.9 % ( P Uncontrolled eating and grazing after surgery showed high overlap and were associated with poorer % WL ( P = 0.008 and P distress . DISCUSSION Consistent with recent studies , uncontrolled eating and grazing were identified as two high-risk eating patterns after surgery . Clearer characterization of favorable and unfavorable postsurgical eating behaviors , reliable methods to assess their presence , and empirically tested postsurgical intervention strategies are required to optimize weight loss outcomes and facilitate psychological well-being in at-risk groups", "OBJECTIVE The aim of this study was to examine whether objective and subjective binges differ significantly from each other in relation to measures of psychopathology in a sample of women who meet DSM-IV diagnostic criteria for bulimia nervosa . METHOD Baseline data from the Eating Disorder Examination ( EDE ) were analyzed and the average of the sum of and the difference between objective and subjective binge episodes were converted to z scores . Regressions were run with other baseline measures including the Structured Clinical Interview for Diagnosis of DSM-III-R ( SCID ) I and II disorders , EDE subscales , and psychological measures . RESULTS We found no significant difference between the two types of binges on all but one measure , the \" Can Do \" subscale of the Self-Efficacy Question naire , in a regression with the z score of total binges . DISCUSSION The lack of significant findings questions the diagnostic validity of the \" large amount of food \" criterion used to define binge eating in the DSM-IV", "OBJECTIVE The objectives of the study were ( 1 ) to determine the prevalence of eating pathology in patients before bariatric surgery and at follow-up ; ( 2 ) to assess the relationship of presurgical eating pathology to various measures of psychopathology ; and ( 3 ) to assess the relationship between presurgical eating pathology and outcome . METHOD One hundred sixteen patients were evaluated prior to surgery and at follow-up an average of 5.5 years after surgery . RESULTS Preoperative binge eating occurred in 52 % of patients , 16 % met criteria for binge eating disorder , and 10 % had the night eating syndrome . All three forms of presurgical eating pathology were statistically associated with cognitive distortions . At follow-up , 33 % of patients were vomiting at least weekly . There was no relationship between presurgical eating pathology and weight outcome or presence of vomiting at follow-up . DISCUSSION Although postoperative vomiting usually does not represent purge behavior , it may represent failed attempts to binge", "Background Binge-eating disorder ( BED ) may be associated with unsatisfactory weight loss in obese patients su bmi tted to bariatric procedures .This study aims to investigate whether the presence of binge eating before Roux-en-Y gastric bypass ( RYGBP ) influences weight outcomes . Methods In a prospect i ve design , 216 obese patients ( 37 males , 178 females , BMI ––5.9 ±–.0 kg/m2 ) were assessed for the lifetime prevalence of BED and classified at structured interview into 3 subgroups : no binge eating ( NBE––3 ) , sub-threshold binge eating ( SBE––29 ) , and binge-eating disorder ( BED––4 ) . All patients were encouraged to take part in a multidisciplinary program following surgery , and weight loss at follow-up was used as the outcome variable . Results At 1-year follow-up , NBE patients ( n––1 ) showed percent excess BMI loss ( % EBL ) significantly higher than SBE patients ( n––12 ) ( P––.027 ) , although this effect was not significantly different between NBE and BED patients ( n––4 ) . At 2-year follow-up , NBE patients ( n––3 ) showed % EBL higher than SBE ( n––4 ) ( P––.003 ) and BED patients ( n––4 ) ( P – lt;–.001 ) . Nevertheless , we found no significant weight loss differences between SBE ( sub clinical ) and BED ( full criteria ) patients at any period of followup . Preliminary results at 3-year follow-up suggest that such an effect may be enduring . Conclusion The presence of a history of binge eating prior to treatment is associated with poorer weight loss in obese patients su bmi tted to RYGBP . Because BED is highly prevalent in obese patients seeking bariatric surgery , its early recognition and treatment may be of important clinical value", "Objective : To investigate the impact of current mental disorders on weight loss with special consideration of depressive and /or anxiety disorders as well as binge eating behavior in obese individuals undergoing different weight loss treatments . Methods : Three different sample s of obese individuals were investigated in a prospect i ve , longitudinal study : participants in a conventional weight loss treatment program ( CONV TREAT ; n = 250 ) , obesity surgery patients ( OBES SURG ; n = 153 ) , and obese control individuals ( OC ; n = 128 ) . Current mental disorders and BMI were assessed at baseline and at 4-year follow-up . Results : OBES SURG patients with a depressive and /or anxiety disorder lost significantly less weight compared with those without a comorbid mental diagnosis . This result was not detected for CONV TREAT participants . A trend to gain weight was seen in OC participants with a depressive and /or anxiety disorder , whereas OC participants without current mental disorders at baseline lost some weight . Binge eating behavior at baseline did not predict weight loss at 4-year followup . Conclusions : These results underline the importance of addressing current depressive and anxiety disorders in obese patients , especially when such patients are undergoing obesity surgery" ]	4118329a-06ff-11f0-808a-c43d1ab1c353
Background : Resistance training ( RT ) is recommended as part of our national physical activity guidelines which includes working all major muscle groups on two or more days a week . Older adults can gain many health benefits from RT , such as increased muscle strength , increased muscle mass , and maintenance of bone density . Additionally , certain dimensions of health-related quality of life ( HRQOL ) have been shown to improve in older adults due to RT intervention . The purpose of this study was to use systematic review and meta-analytic techniques to examine the effect of RT on HRQOL in older adults . Methods : A systematic review of current studies ( 2008 thru 2017 ) was conducted using PubMed . Studies were included if they used a r and omized controlled design , had RT as an intervention , measured HRQOL using the SF-36/12 assessment , and included adults 50 + years of age . Eight dimension scores ( physical functioning , bodily pain , physical role function , general health , mental health , emotional role function , social function , and vitality ) and two summary scores ( physical component and mental component ) were extracted . Ten meta-analyses were performed using st and ardized mean effect sizes and r and om effects models . Study quality , moderator and sensitivity analyses were conducted . Results : A total of 16 studies were included in the analyses with a mean Physiotherapy Evidence Data base ( PEDro ) score of 4.9 ( SD=1.0 ) . Among the mental health measures , RT had the greatest effect on mental health ( Effect size [ES]=0.64 , 95 % CI : 0.30 - 0.99 , I2=79.7 ) . Among the physical health measures , RT had the largest effect on body pain ( ES=0.81 , 95 % CI : 0.26 - 1.35 , I2=85.9).Initially , RT did not significantly affect measures of emotional role function , social function or physical role function . However , after removing a single study , RT significantly increased all HRQOL measures . Conclusion : The meta-analytic evidence presented in this research clearly supports the promotion of RT in improving HRQOL in older adults	[ "Introduction Physical activity in elderly persons contributes to prevention and treatment of chronic disease and , through its influence on the musculoskeletal system , increases physical capability and improves mental function . Aim of the study Aim of the study was to assess the effect of resistance training with elements of stretching on body composition and quality of life in women of postmenopausal age . Material and methods Thirty-eight postmenopausal women aged 62.5 ±5.8 years were r and omly divided into two groups . One group participated in an 8-week training program ( 60 minutes , twice weekly ; 4 MET [ metabolic equivalent ] 2 hours/week ) . The second group performed no training . A comparison was made of body composition and quality of life ( SF-36 Health Survey ) prior to and after 8 weeks of training . Results In the training group , after 8 weeks there was a significant reduction in body fat ( in% ; p = 0.028 ) , and an increase in fat-free mass ( in% ; p = 0.025 ) and total body water ( in% ; p = 0.021 ) , which indicates increased muscle mass . Furthermore , there were statistically significant differences in the assessment of quality of life in physical ( role-physical [ RP ] , bodily pain [ BP ] , general health [ GH ] scales ; p 0.005 ) and mental health ( vitality [ VT ] scale ; p = 0.05 ) . In the non-exercising group no changes were observed in features examined in the initial and final test . Conclusions Resistance training with elements of stretching in postmenopausal women improved body composition to achieve a reduction in risk factors associated with excess fatty tissue and muscle mass deficiency . It raises the quality of life in terms of both physical and mental function", "BACKGROUND Exercise is important as adjuvant in the chronic low back pain ( CLBP ) treatment . Functional training could involve benefits for low back pain ( LBP ) patients . OBJECTIVE To evaluate the effects of a 12-week period of functional resistance training on health-related quality of life ( HRQOL ) , disability , body pain , and physical fitness in CLBP females . METHODS Nineteen females CLBP were recruited according to Paris Task Force on Back Pain criteria . Participants were r and omly assigned to an exercise group ( EG ) ; and a control group ( CG ) . Subjects were tested at baseline and at week 12 after 24 sessions , 2 days per week . Body pain was assessed using visual analog scale ( VAS ) , disability with Oswestry Disability Index ( ODI ) and HRQOL with Short Form 36 question naire . Physical fitness was measured using : flamingo test , back endurance test , side bridge test , abdominal curl-up tests , and 60-s squat test . RESULTS EG showed significant improvements in physical function ( 10 % ; p body pain ( 42 % ; p vitality ( 31 % ; p physical component scale ( 15 % ; p VAS ( 62.5 % ; p ODI ( 61.3 % ; p balance ( 58 % ; p curl-up ( 83 % ; p squat ( 22 % ; p static back ( 67 % ; p side bridge ( 56 % ; p Periodized functional resistance training decreased pain and disability and improved HRQOL , balance and physical fitness in females with CLBP , and can thus be used safely in this population", "Purpose ( 1 ) To determine the effects of a 9-month resistance training intervention on quality of life , sense of coherence , and depressive symptoms in older adults , and ( 2 ) to compare effects between different training frequencies . Methods Men and women aged 65–75 ( N = 106 ) were r and omized to four groups according to training frequency : training groups RT1 ( n = 26 ) , RT2 ( n = 27 ) , and RT3 ( n = 28 ) and non-training control group ( n = 25 ) . All training groups attended supervised resistance training twice a week for 3 months . For the following 6 months , they continued training with different frequencies ( 1 , 2 or 3 times per week ) . Psychological functioning was measured by quality of life ( WHOQOL-Bref ) , sense of coherence ( Antonovsky ’s SOC-13 ) , and depressive symptoms ( Beck ’s Depression Inventory II ) . Measurements were conducted at baseline and 3 and 9 months after baseline . The effects of the intervention were analyzed using generalized estimating equations ( GEE ) . Results After 3 months , there was an intervention effect on environmental quality of life ( group × time p = .048 ) . Between 3 and 9 months , environmental quality of life decreased among RT1 compared to RT2 and RT3 ( group × time p = .025 ) . Between baseline and 9 months , environmental quality of life increased in RT2 compared to all other groups ( group × time p = .011 ) . Sense of coherence increased in RT2 compared to the control group and RT3 ( group × time p = .032 ) . Conclusion Resistance training is beneficial for environmental quality of life and sense of coherence . Attending resistance training twice a week seems to be the most advantageous for these aspects of psychological functioning", "ABSTRACT Background Sarcopenic obesity is associated with disability in older people , especially in women . Resistance exercises are recommended for this population , but their efficacy is not clear . Objective To evaluate the effects of a progressive resistance exercise program with high-speed component on the physical function of older women with sarcopenic obesity . Method Twenty-eight women 65 to 80 years old , with a body mass index ≥30kg/m2 and h and grip strength ≤21 kg were r and omly allocated to two groups . The experimental group underwent a 10-week resistance exercise program design ed to improve strength , power , and endurance of lower-limb muscles , with open chain and closed chain exercises . The control group had their health status monitored through telephone calls . The primary outcomes were lower limb muscle performance measured by knee extensor strength , power and fatigue by isokinetic dynamometry , and mobility measured by the Short Physical Performance Battery and by gait velocity . The secondary outcome was health-related quality of life assessed by the SF-36 Question naire . Results The average rate of adherence was 85 % , with few mild adverse effects . There were no significant between-group differences for any of the outcomes . Conclusion In this study , a progressive resistance exercise program with high-speed component was not effective for improving the physical function of older women with sarcopenic obesity", "Strength training has been reported as a potentially useful exercise to improve psychological aspects in the elderly , but its effects remain controversial . This study investigated the effectiveness of strength training conducted twice a week for 12 weeks for improving health-related quality of life ( HRQOL ) and executive cognitive function . The study was a single-blind r and omized controlled trial with assessment s before and after intervention . HRQOL and executive function were assessed using the SF-36 Health Status Survey and a computerized neuro-cognitive assessment using task-switch reaction time trials , respectively . Subjects comprised 119 participants > or = 65 years old , r and omized to either strength training ( n=65 ) or health education classes ( controls , n=54 ) . The strength training program was design ed to strengthen the large muscle groups most important for functional activities and to improve balance . The effects of the intervention on the eight dimensions of the SF-36 in the control and training groups were analyzed . Only the mental health scale of the SF-36 was significantly improved for the training group compared with controls after 12 weeks . Task-switch reaction time and correct response rate remained unchanged . Short-term strength training might have modest positive effects on HRQOL , although this training period may not be sufficient to affect executive function in relatively healthy older people", "INTRODUCTION Increased physical activity ( PA ) is a crucial factor in the prevention of physical deterioration , and resistance training ( RT ) is also a common and effective intervention for older adults . However , the effects of PA as an adjunct to RT on frailty status remains unclear ; therefore , we clarified the effect of a PA intervention with feedback , as an adjunct to resistance strength training , on the physical and mental outcomes of frail older adults . MATERIAL S AND METHODS We employed a r and omized controlled trial . Community-dwelling frail older adults in Japan were recruited to participate . Forty-one participants ( mean age 81.5 ) were r and omly assigned to engage in a resistance training with PA ( RPA group ) or RT group for six months . Frailty status and frailty scores , which were measured according to the Cardiovascular Health Study criteria -muscle strength , mobility , instrumental activities of daily living , and health-related quality of life-were assessed . RESULTS Participants in the RPA group exhibited a significant increase in light-intensity PA , the number of steps taken daily ( p lower-limb muscle strength ( p significant decrease in frailty scores . However , pre- and postintervention frailty status , instrumental activities of daily living , and health-related quality of life did not differ significantly . CONCLUSIONS Implementation of a PA intervention as an adjunct to RT is feasible , as it reduced frailty scores and increased lower-limb muscle strength and mobility in older adults with frailty symptoms", "Background Prostate cancer can negatively impact quality of life of the patient and his spouse caregiver , but interventions rarely target the health of both partners simultaneously . We tested the feasibility and preliminary efficacy of a partnered strength training program on the physical and mental health of prostate cancer survivors ( PCS ) and spouse caregivers . Methods Sixty-four couples were r and omly assigned to 6 months of partnered strength training ( Exercising Together , N = 32 ) or usual care ( UC , N = 32 ) . Objective measures included body composition ( lean , fat and trunk fat mass ( kg ) , and % body fat ) by DXA , upper and lower body muscle strength by 1-repetition maximum , and physical function by the physical performance battery ( PPB ) . Self-reported measures included the physical and mental health summary scales and physical function and fatigue subscales of the SF-36 and physical activity with the CHAMPS question naire . Results Couple retention rates were 100 % for Exercising Together and 84 % for UC . Median attendance of couples to Exercising Together sessions was 75 % . Men in Exercising Together became stronger in the upper body ( p more physically active ( p increased muscle mass ( p = 0.05 ) and improved upper ( p 0.01 ) and lower body ( p ( p = 0.01 ) more than UC . Conclusions Exercising Together is a novel couples-based approach to exercise that was feasible and improved several health outcomes for both PCS and their spouses . Implication s for cancer survivorsA couples-based approach should be considered in cancer survivorship programs so that outcomes can mutually benefit both partners . Trial registration Clinical Trials.gov", "BACKGROUND Resistance training programs have been found to improve muscle strength , physical function , and depressive symptoms in middle-aged and older adults . These programs have typically been provided in clinical facilities , health clubs , and senior centers , which may be inconvenient and /or cost prohibitive for some older adults . The purpose of this study was to investigate the effectiveness of an automated telemedicine intervention that provides real-time guidance and monitoring of resistance training in the home . METHODS A r and omized clinical trial in 103 middle-aged or older participants . Participants were assigned to use of a theory-driven interactive voice response system design ed to promote resistance training ( Telephone-Linked Computer-based Long-term Interactive Fitness Trainer ; n = 52 ) or to an attention control ( n = 51 ) for a period of 12 months . Measurements of muscle strength , balance , walk distance , and mood were obtained at baseline , 3 , 6 , and 12 months . RESULTS We observed increased strength , improved balance , and fewer depressive symptoms in the intervention group than in the control group . Using generalized estimating equations modeling , group differences were statistically significant for knee flexion strength ( p = .035 ) , single-leg stance time ( p = .029 ) , and Beck Depression Inventory ( p = .030 ) . CONCLUSIONS This computer-based telecommunications exercise intervention led to improvements in participants ' strength , balance , and depressive symptoms . Because of their low cost and easy accessibility , computer-based interventions may be a cost-effective way of promoting exercise in the home", "Summary This study aims to evaluate the effect of 18-week progressive muscular strength and proprioception training program on the muscle strength of the quadriceps , in prevention of falls in postmenopausal women with osteoporosis . The incidence of falls in the intervention group was significantly lower than in the control group ( incidence rate ratio ( IRR ) = 0.263 , 95 % CI 0.10–0.68 ) . Introduction This study aims to evaluate the effect of a progressive muscular strength and proprioception training program on the muscle strength of the quadriceps , balance , quality of life , and reduction in the risk of falls in postmenopausal women with osteoporosis . Methods One hundred sedentary postmenopausal women with osteoporosis , ages ranging from 55 to 75 , were selected and r and omized into two groups : the intervention group comprised of 50 patients who underwent a 18-week of progressive load training for the quadriceps muscle ( 50 % up to 80 % of 1-RM — one maximum repetition ) and proprioception training associated to a drug treatment of osteoporosis and the control group that included 50 patients who only underwent a drug treatment of osteoporosis . The muscular strength , balance , functional mobility , and quality of life were evaluated in the beginning and end of the research . The number of falls was evaluated 24 weeks post-treatment . Results Eighty-five patients concluded the research . The program promoted a significant difference among the groups for SF-36 in the eight sub-scales ( p ≤ 0.0018 ) , Timed Up & Go Test ( p 1-RM test ( p 0.0001 ) , Berg Balance Scale ( p decrease in the number of falls in the intervention group compared to control ( IRR = 0.263 , 95 % CI 0.10–0.68 , p = 0.0064 ) . Conclusion The association of progressive strength training for the quadriceps and the proprioceptive training is effective for the prevention of falls , increasing the muscle power , the static and dynamic balance and increasing the speed of the motor responses , therefore improving the performance of daily activities", "This article compared the effect of dietary weight loss administered alone ( WL ) or in combination with aerobic training ( WL + AT ) or resistance training ( WL + RT ) on health related quality of life , walking self-efficacy , stair climb self-efficacy , and satisfaction with physical function in older adults with cardiovascular disease or the metabolic syndrome . Participants ( N = 249 ; Mage = 66.9 ) engaged in baseline assessment s and were r and omly assigned to one of three interventions , each including a 6-month intensive phase and a 12-month follow-up . Those in WL + AT and WL + RT engaged in 4 days of exercise training weekly . All participants engaged in weekly group behavioral weight loss sessions with a goal of 7–10 % reduction in body weight . Participants in WL + AT and WL + RT reported better quality of life and satisfaction with physical function at 6- and 18-months relative to WL . At month 6 , WL + AT reported greater walking self-efficacy relative to WL + RT and WL , and maintained higher scores compared to WL at month 18 . WL + AT and WL + RT reported greater stair climbing efficacy at month 6 , and WL + RT remained significantly greater than WL at month 18 . The addition of either AT or RT to WL differentially improved HRQOL and key psychosocial outcomes associated with maintenance of physical activity and weight loss . This underscores the important role of exercise in WL for older adults , and suggests health care providers should give careful consideration to exercise mode when design ing interventions", "QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis", "Objective To assess the effectiveness of a two year exercise programme of progressive balance retraining in reducing injurious falls among women aged 75 - 85 at increased risk of falls and injuries and living in the community . Design Pragmatic multicentre , two arm , parallel group , r and omised controlled trial . Setting 20 study sites in 16 medium to large cities throughout France . Participants 706 women aged 75 - 85 , living in their own home , and with diminished balance and gait capacities , r and omly allocated to the experimental intervention group ( exercise programme , n=352 ) or the control group ( no intervention , n=354 ) . Intervention Weekly supervised group sessions of progressive balance training offered in community based premises for two years , supplemented by individually prescribed home exercises . Outcome measures A geriatrician blinded to group assignment classified falls into one of three categories ( no consequence , moderate , severe ) based on physical damage and medical care . The primary outcome was the rate of injurious falls ( moderate and severe ) . The two groups were compared for rates of injurious falls with a “ shared frailty ” model . Other outcomes included the rates of all falls , physical functional capacities ( balance and motor function test results ) , fear of falling ( FES-I ) , physical activity level , and perceived health related quality of life ( SF-36 ) . Analysis was by intention to treat . Results There were 305 injurious falls in the intervention group and 397 in the control group ( hazard ratio 0.81 , 95 % confidence interval 0.67 to 0.99 ) . The difference in severe injuries ( 68 in intervention group v 87 in control group ) was of the same order of magnitude ( 0.83 , 0.60 to 1.16 ) . At two years , women in the intervention group performed significantly better on all physical tests and had significantly better perception of their overall physical function than women in the control group . Among women who started the intervention ( n=294 ) , the median number of group sessions attended was 53 ( interquartile range 16 - 71 ) . Five injurious falls related to the intervention were recorded . Conclusion A two year progressive balance retraining programme combining weekly group and individual sessions was effective in reducing injurious falls and in improving measured and perceived physical function in women aged 75 - 85 at risk of falling . Trial registration Clinical Trials.gov ( NCT00545350 )", "UNLABELLED Movement therapy during the rehabilitation of breast cancer has become more important over the last years . PATIENTS AND METHODS In a r and omized controlled study the feasibility of gentle strenght training was compared to conventional gymnastic exercises during rehabilitation of breast cancer patients . The aim oft this study was to identify alternative sports intervention in the treatment of breast cancer patients . The intervention group ( IG ) was lifting st and ardized weights weekly ( 50 % of h1RM ) , while the control group ( CG ) received conventional gymnastic exercises . A bicycle ergometry adjusted to the WHO system was performed with all participants at study entry ( T0 ) , after three ( T1 ) and six months ( T2 ) . The quality of life was measured by st and ardized report forms ( EORTC QLQ C30 Version 3 and BR23 ) . RESULTS Both methods showed a slight improvement in submaximal endurance performance , a significant improvement in the subjective feeling of effort ( IG : 75 W : psychosocial and psychological parameters like quality of life ( IG : in fatigue ( IG : of breast cancer patients and turned out to be a probate alternative to gymnastic exercises", "Objective : Menopause induces a phase of decreased physical fitness and altered body composition characterized by increased total and abdominal fat and reduced lean mass . It is , however , inconclusive which specific resistance training ( RT ) subtypes can reverse these deleterious changes in postmenopausal women . Methods : Thirty-seven postmenopausal women were r and omized to a 6-week nonexercising control group ( n = 18 ) or hypertrophic RT group ( n = 19 ) that engaged in two 40-minute sessions weekly using three sets of 12 repetitions at 67 % to 85 % one-repetition maximum for 10 whole-body exercises . Results : RT significantly improved resting heart rate ( 69.05 ± 11.19 - 63.80 ± 4.94 bpm , P = 0.017 ) , systolic blood pressure ( 125.85 ± 4.86 - 124.05 ± 3.98 mm Hg , P ( 81.20 ± 7.50 - 77.90 ± 6.85 mm Hg , P product ( 8,712.40 ± 1,408.21 - 7,952.90 ± 782.72 , P = 0.003 ) , blood glucose concentration ( 6.06 ± 0.52 - 5.70 ± 0.52 mmol/L , P = 0.009 ) , fat mass ( 21.53 ± 7.07 - 19.75 ± 6.40 kg , P = 0.001 ) , percentage body fat ( 30.66 % ± 5.08%-25.49 % ± 9.89 % , P = 0.026 ) , body mass index ( 24.50 ± 3.85 - 24.27 ± 4.04 kg/m2 , P = 0.050 ) , waist circumference ( 80.04 ± 8.57 - 73.19 ± 18.44 cm , P = 0.045 ) , sum of skinfolds ( 22.91 ± 6.05 - 20.72 ± 5.26 mm , P strength ( 20.12 ± 5.65 - 23.77 ± 7.10 kg , P ( 16.28 ± 5.47 - 16.44 ± 5.62 kg , P = 0.001 ) muscle strength . Conclusions : A 6-week hypertrophic RT program , performed even twice weekly , produces substantial simultaneous improvements in multiple anthropometric , cardiovascular , and muscle strength variables in postmenopausal women . This program can be recommended for inclusion in any exercise training regime or as an adjunct lifestyle approach in combination with other treatments in postmenopausal women", "AIM This study compared the effect of different resistance training ( RT ) frequencies on total , and roid , gynoid and trunk body fat in overweight/obese older women . METHODS Fifty-seven overweight/obese older women ( 66.9±5.3 years and 39.9±4.9 % body fat ) were r and omly assigned to one of three groups : a group performing RT twice a week ( G2X ) , a group performing RT three times a week ( G3X ) , or a non-exercise control group ( CG ) . Both training groups performed the same 12-week RT program consisting of 8 exercises that trained all major muscle groups . Dual-energy X-ray absorptiometry was used to assess body composition . RESULTS After the intervention period , both G2X and G3X demonstrated significant ( P reductions in adiposity compared to the CG for total body fat ( G2X=-1.7 % , G3X=-2.7 % , CG=+2.1 % ) , and roid fat ( G2X=-6.2 % , G3X=-7.0 % , CG=+8.6 % ) , gynoid fat ( G2X=-2.5 % , G3X=-2.9 % , CG=+1.0 % ) , and trunk fat ( G2X=-2.5 % , G3X=-3.0 % , CG=+2.9 % ) , with no significant differences between training groups . CONCLUSION These results demonstrate that a low-volume 12-week RT program performed two or three times per week causes decreases in total and regional fat deposition with the greatest reductions occurring in the and roid region", "Abstract Purpose : To investigate if combined strength and aerobic training can enhance aerobic capacity in the elderly to a similar extent as aerobic training alone when training duration is matched . Methods : Elderly men and women ( age 63.2 ± 4.7 ) were r and omized into two intervention groups : an aerobic group ( AG , n = 17 ) and a combined group ( CG , n = 16 ) . Subjects trained 40 minutes three times a week for 12 weeks . Both groups trained 20 minutes at 65 % of heart rate reserve on ergometer cycles followed by another 20 minutes on the ergometer cycles for AG and 20-minute strength training for the lower body for CG . The primary outcome was VO2max . Secondary outcomes were maximal voluntary contraction ( MVC ) in isometric knee extension , 1 repetition maximum in three leg exercises , body fat , waist-to-hip ratio , blood pressure and score on the Health Survey Short Form 36 ( SF-36 ) . Results : Both groups improved VO2max ( p .01 ) and MVC ( p increased 17 % confidence interval ( CI ) [ 7.4–26 ] in CG and 26 % CI [ 14.1–38.2 ] in AG , with no significant difference between groups . MVC increased 22 % CI [ 16.3–27.7 ] in CG and 9 % CI [ 4.6–13.5 ] in AG with CG improving MVC more than AG ( p health survey improved more than AG 's score . Conclusion : Elderly can substitute a part of their aerobic training with strength training and still improve VO2max to a clinical ly significant degree when strength training is performed with large muscle groups subsequently to the aerobic training . Combined training additionally improves strength and self-assessed general health more than aerobic training alone", "OBJECTIVE To determine the impact of a 16 week high-intensity progressive resistance exercise training ( PRT ) program on the mental health of older Puerto Rican adults with type 2 diabetes . METHODS Fifty-eight Puerto Rican adults were r and omly assigned to supervised PRT ( n = 29 ) or a control group ( n = 29 ) . A secondary analyses were conducted , and 2 mental health outcomes , the Geriatric Depression Scale and the SF-36 mental component summary score , were used to assess the impact of PRT on mental health status . At baseline , no differences were found on measures of self-reported mental health status . RESULTS PRT participants had significantly improved mental health status at follow-up ( 16 weeks ) . DISCUSSION The incorporation of exercise into treatment planning for older adults may have important benefits on their mental health status . More work is needed to underst and the mechanisms by which this occurred as well as the applicability of these findings to sustainable community programs", "CONTEXT Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease ( PAD ) without intermittent claudication have been established as beneficial . OBJECTIVE To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled clinical trial performed at an urban academic medical center between April 1 , 2004 , and August 8 , 2008 , involving 156 patients with PAD who were r and omly assigned to supervised treadmill exercise , to lower extremity resistance training , or to a control group . MAIN OUTCOME MEASURES Six-minute walk performance and the short physical performance battery . Secondary outcomes were brachial artery flow-mediated dilation , treadmill walking performance , the Walking Impairment Question naire , and the 36-Item Short Form Health Survey physical functioning ( SF-36 PF ) score . RESULTS For the 6-minute walk , those in the supervised treadmill exercise group increased their distance walked by 35.9 m ( 95 % confidence interval [ CI ] , 15.3 - 56.5 m ; P distance walked by 12.4 m ( 95 % CI , -8.42 to 33.3 m ; P = .24 ) compared with the control group . Neither exercise group improved its short physical performance battery scores . For brachial artery flow-mediated dilation , those in the treadmill group had a mean improvement of 1.53 % ( 95 % CI , 0.35%-2.70 % ; P = .02 ) compared with the control group . The treadmill group had greater increases in maximal treadmill walking time ( 3.44 minutes ; 95 % CI , 2.05 - 4.84 minutes ; P walking impairment distance score ( 10.7 ; 95 % CI , 1.56 - 19.9 ; P = .02 ) ; and SF-36 PF score ( 7.5 ; 95 % CI , 0.00 - 15.0 ; P = .02 ) than the control group . The resistance training group had greater increases in maximal treadmill walking time ( 1.90 minutes ; 95 % CI , 0.49 - 3.31 minutes ; P = .009 ) ; walking impairment scores for distance ( 6.92 ; 95 % CI , 1.07 - 12.8 ; P = .02 ) and stair climbing ( 10.4 ; 95 % CI , 0.00 - 20.8 ; P = .03 ) ; and SF-36 PF score ( 7.5 ; 95 % CI , 0.0 - 15.0 ; P = .04 ) than the control group . CONCLUSIONS Supervised treadmill training improved 6-minute walk performance , treadmill walking performance , brachial artery flow-mediated dilation , and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication . Lower extremity resistance training improved functional performance measured by treadmill walking , quality of life , and stair climbing ability . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00106327", "Loss of function and low exercise adherence is common among older people after hospitalization . The aim of this r and omized-controlled trial was to evaluate the effects of a combined counseling- and exercise program on changes in health-related quality of life ( HRQL ) and physical function in patients attending a day hospital and continuing exercise at home . The exercise program consisted of counseling , balance- and progressive resistance training and support from the physical therapist at Geriatric Day-Hospital ( GDH ) and home for the Intervention-group . The Control-group received counseling , balance-training and support from the physical therapist . The sample was recruited from a GDH in Norway . 108 participants were r and omized into the Intervention group ( IT ) ( n=53 ) or the Control group ( CT ) ( n=55 ) . After 3 months 77 participants were tested . The intention to treat analysis showed that the program had significant benefits in terms of Health Related Quality of Life , measured by SF-36 , on the domains vitality and bodily pain , in favor of the IT-group who performed the combined resistance exercises and balance program . All participants increased their scores on physical function , measured by Berg Balance Scale , Timed Up and Go , 5 times Sit-to-St and , 6 Min Walk Test and Activities Balance Confidence Scale , no group differences . Both groups were adherent to the home exercise program The results show that it is possible to facilitate older people to increase their HRQL , physical function and level of physical activity through counseling , exercise and support from physical therapists", "This study aim ed to investigate the effects of training on health-related quality of life ( HRQoL ) , body composition , and function in older adults . Fifty participants were r and omized into aerobic training ( AT—70%-80 % HRreserve ) , resistance training ( RT—80 % 1RM ) , or controls . They had HRQoL , body composition , and function assessed before and after 8 months . Training groups reduced body fat , increased performance in the stair ascent , 8-ft up- and -go and sit-to-st and five-times tests , and improved their physical component score ( PCS ; p ≤ .03 ) . AT increased performance in the 6MWT test , and improved general and mental health ( MH ) domains when compared to controls ( p with changes in bodily pain , MH , and mental component score ( p ≤ .04 ) , while changes in h and grip strength were associated with changes in physical role and MH ( p = .03 ) . AT and RT were effective interventions for decreasing body fat and improving functionality and the PCS in older adults ", "RATIONALE Excess mortality and residual disability are common after hip fracture . HYPOTHESIS Twelve months of high-intensity weight-lifting exercise and targeted multidisciplinary interventions will result in lower mortality , nursing home admissions , and disability compared with usual care after hip fracture . DESIGN R and omized , controlled , parallel-group superiority study . SETTING Outpatient clinic PARTICIPANTS Patients ( n = 124 ) admitted to public hospital for surgical repair of hip fracture between 2003 and 2007 . INTERVENTION Twelve months of geriatrician-supervised high-intensity weight-lifting exercise and targeted treatment of balance , osteoporosis , nutrition , vitamin D/calcium , depression , cognition , vision , home safety , polypharmacy , hip protectors , self-efficacy , and social support . OUTCOMES Functional independence : mortality , nursing home admissions , basic and instrumental activities of daily living ( ADLs/IADLs ) , and assistive device utilization . RESULTS Risk of death was reduced by 81 % ( age-adjusted OR [ 95 % CI ] = 0.19 [ 0.04 - 0.91 ] ; P HIPFIT group ( n = 4 ) compared with usual care controls ( n = 8) . Nursing home admissions were reduced by 84 % ( age-adjusted OR [ 95 % CI ] = 0.16 [ 0.04 - 0.64 ] ; P Basic ADLs declined less ( P assistive device use was significantly lower at 12 months ( P = .02 ) in the intervention group compared with controls . The targeted improvements in upper body strength , nutrition , depressive symptoms , vision , balance , cognition , self-efficacy , and habitual activity level were all related to ADL improvements ( P basic ADLs , vision , and walking endurance were associated with reduced nursing home use ( P HIPFIT intervention reduced mortality , nursing home admissions , and ADL dependency compared with usual care", "The objectives of this research were to develop an aerobic step combined with resistance training exercise program , and to compare the effects of A ) aerobic step exercise training ( STE ) , B ) resistance aerobic exercise training ( RES ) , C ) a combined aerobic step with resistance exercise training ( COM ) on the health-related fitness , balance , and biochemical bone markers . Sixty participants were working female volunteers at the age of 35 - 45 . They were divided into 4 groups by simple r and om sampling method . Fifteen of the participants were in the STE group , 14 in the RES group , 15 in the COM group , and 16 in the control group ( CON ) . The STE , RES and COM exercise training programs were design ed to yield the same intensity and achieve the same range of heart rate during each stage of the program . During the training , music was used to set the tempo of the workouts . At the 8th week , it was found that resting heart rate and systolic blood pressure significantly-increased only in the STE and COM groups . After 16 weeks , the experiment results showed the significant improvement in the COM and STE groups of exercise training for β-CrossLaps , P1NP NMID Osteocalcin and bone formation ( PINP/β-CrossLaps x0.31 ) but not in the RES group . For balance ability , the COM group showed significantly greater change than the RES group after the training intervention ( p the STE and COM training were effective in improving bone formation ( PINP/β-CrossLaps x 0.31 ) but not in the RES group . For balance ability , the COM group showed more significant change than the RES group . Therefore , this is not only a good exercise choice for the working-age people but also it can help reduce the risks of osteoporosis and falling in women in particular", "BACKGROUND Previous studies suggest that qigong therapy has physiological benefits for adults with type 2 diabetes ; however , information about the psychological benefits of qigong therapy in this population is limited . OBJECTIVE The objective of this research project was to identify psychological responses to qigong vs control interventions in adults with type 2 diabetes . DESIGN The research team design ed a r and omized , controlled , three-arm clinical trial comparing 12 weeks of Yi Ren Medical Qigong ( YRMQ ) , progressive resistance training ( PRT ) , and st and ard care . SETTING The study was performed at Bastyr University Research Institute , Kenmore , Washington . PARTICIPANTS Participants were 13 men and 19 women ( N=32 ) with diagnosed type 2 diabetes , a mean age of 56.3 ± 8.1 ( st and ard deviation ) years , glycated hemoglobin > 7.5 % , and fasting blood glucose > 7 mmol/dL ( 126 mg/dL ) . INTERVENTION For 12 weeks , participants in the YRMQ and PRT group attended a 1-hour weekly group session that a certified instructor led and were instructed to practice at least twice a week for 30 minutes . PRIMARY OUTCOME MEASURES The research team used the Perceived Stress Scale and the Beck Depression Inventory scores to analyze the data . RESULTS YRMQ decreased perceived-stress scores by 29.3 % ( P .05 ) and depression scores by 14.3 % ( not significant [ NS ] ) . The active control group , PRT , also decreased stress scores by 18.6 % ( NS ) and decreased depression scores by 50 % ( P measures remained unchanged in the st and ard care group . CONCLUSION YRMQ and PRT may be beneficial in reducing perceived stress and improving depression in patients with type 2 diabetes , although verification of the clinical significance of these findings requires a longer study with a larger sample size", "OBJECTIVES To compare the effectiveness of a short-term leg-strengthening exercise program with that of attentional control on improving strength , walking abilities , and function 1 year after hip fracture . DESIGN R and omized controlled pilot study . SETTING Patients ' homes . PARTICIPANTS Community-dwelling older adults ( n=26 ) 6 months after hip fracture at baseline . INTERVENTION Exercise and control participants received interventions from physical therapists twice a week for 10 weeks . The exercise group received high-intensity leg-strengthening exercises . The control group received transcutaneous electrical nerve stimulation and mental imagery . MEASUREMENTS Isometric force production of lower extremity muscles , usual and fast gait speed , 6-minute walk ( 6-MW ) distance , modified Physical Performance Test ( mPPT ) , and Medical Outcomes Study 36-item Short Form Survey ( SF-36 ) physical function . RESULTS The primary endpoint was 1 year after fracture . Isometric force production ( P=.006 ) , usual ( P=.02 ) and fast ( P=.03 ) gait speed , 6-MW distance ( P=.005 ) , and mPPT score ( P exercise . Effect sizes were 0.79 for strength , 0.81 for mPPT score , 0.56 for gait speed , 0.49 for 6-MW , and 0.30 for SF-36 score . More patients in the exercise group made meaningful changes in gait speed and 6-MW distance than control patients ( chi-square P=.004 ) . CONCLUSION A 10-week home-based progressive resistance exercise program was sufficient to achieve moderate to large effects on physical performance and quality of life and may offer an alternative intervention mode for patients with hip fracture who are unable to leave home by 6 months after the fracture . The effects were maintained at 3 months after completion of the training program", "ABSTRACT Background : Falls are associated with morbidity , loss of independence , and mortality . While l and -based group exercise and Tai Chi programs reduce the risk of falls , aquatic therapy may allow patients to complete balance exercises with less pain and fear of falling ; however , limited data exist . Objective : The objective of the study was to pilot the implementation of an aquatic group based on Ai Chi principles ( Aquabalance ) and to evaluate the safety , intervention acceptability , and intervention effect sizes . Design : Pilot observational cohort study . Methods : Forty-two out patients underwent a single 45-minute weekly group aquatic Ai Chi-based session for eight weeks ( Aquabalance ) . Safety was monitored using organizational reporting systems . Patient attendance , satisfaction , and self-reported falls were also recorded . Balance measures included the Timed Up and Go ( TUG ) test , the Four Square Step Test ( FSST ) , and the unilateral Step Tests . Results : Forty-two patients completed the program . It was feasible to deliver Aquabalance , as evidence d by the median ( IQR ) attendance rate of 8.0 ( 7.8 , 8.0 ) out of 8 . No adverse events occurred and participants reported high satisfaction levels . Improvements were noted on the TUG , 10-meter walk test , the Functional Reach Test , the FSST , and the unilateral step tests ( p high falls risk reduced from 38 % to 21 % . The study was limited by its small sample size , single-center nature , and the absence of a control group . Conclusions : Aquabalance was safe , well-attended , and acceptable to participants . A r and omized controlled assessor-blinded trial is required", "OBJECTIVES To assess the effects of resistance training on the anxiety symptoms and quality of life in patients with Parkinson 's disease . METHODS Thirty-five elderly patients were r and omly divided into two groups : 17 patients in the control group and 18 in the intervention group . All patients maintained st and ard pharmacological treatment for Parkinson 's disease , but the intervention group participated in a 24-week resistance training program . The anxiety symptoms were assessed through the Beck 's Anxiety Inventory , and quality of life by the Parkinson 's Disease Question naire-39 . RESULTS There was a significant reduction in anxiety level and increase in quality of life after 24 weeks of resistance training . CONCLUSION The results of the present study indicate that resistance training is an effective intervention in the reduction of anxiety symptoms and improves the quality of life in elderly people with Parkinson 's disease" ]	41183312-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Diabetes is a common chronic disease that is increasingly managed in primary care . Different systems have been proposed to manage diabetes care . OBJECTIVES To assess the effects of different interventions , targeted at health professionals or the structure in which they deliver care , on the management of patients with diabetes in primary care , outpatient and community setting s. SEARCH STRATEGY We search ed the Cochrane Effective Practice and Organisation of Care Group specialised register , the Cochrane Controlled Trials Register ( Issue 4 1999 ) , MEDLINE ( 1966 - 1999 ) , EMBASE ( 1980 - 1999 ) , Cinahl ( 1982 - 1999 ) , and reference lists of articles . SELECTION CRITERIA R and omised trials ( RCTs ) , controlled clinical trials ( CCTs ) , controlled before and after studies ( CBAs ) and interrupted time series ( ITS ) analyses of professional , financial and organisational strategies aim ed at improving care for people with Type 1 or Type 2 diabetes . The participants were health care professionals , including physicians , nurses and pharmacists . The outcomes included objective ly measured health professional performance or patient outcomes , and self-report measures with known validity and reliability . DATA COLLECTION AND ANALYSIS Two review ers independently extracted data and assessed study quality . MAIN RESULTS Forty-one studies were included involving more than 200 practice s and 48,000 patients . Twenty-seven studies were RCTs , 12 were CBAs , and two were ITS . The studies were heterogeneous in terms of interventions , participants , setting s and outcomes . The method ological quality of the studies was often poor . In all studies the intervention strategy was multifaceted . In 12 studies the interventions were targeted at health professionals , in nine they were targeted at the organisation of care , and 20 studies targeted both . In 15 studies patient education was added to the professional and organisational interventions . A combination of professional interventions improved process outcomes . The effect on patient outcomes remained less clear as these were rarely assessed . Arrangements for follow-up ( organisational intervention ) also showed a favourable effect on process outcomes . Multiple interventions in which patient education was added or in which the role of the nurse was enhanced also reported favourable effects on patients ' health outcomes . REVIEW ER 'S CONCLUSIONS Multifaceted professional interventions can enhance the performance of health professionals in managing patients with diabetes . Organisational interventions that improve regular prompted recall and review of patients ( central computerised tracking systems or nurses who regularly contact the patient ) can also improve diabetes management . The addition of patient-oriented interventions can lead to improved patient health outcomes . Nurses can play an important role in patient-oriented interventions , through patient education or facilitating adherence to treatment	[ "Sustained improvement in blood glucose control is the only treatment outcome which will reduce or eliminate the long term complications of diabetes mellitus . We have design ed and evaluated an electronic information system which facilitates this task . The system is voice-interactive , physician directed and affords , to remote patients , 24 h access via touch-tone telephone . Accordingly , patients access the system each day to report self-measured blood glucose levels or hypoglycaemic symptoms together with dietary changes , planned exercise , stress , illness or other lifestyle events . In turn they receive immediate advice with respect to medication dosing changes , and other pertinent feedback . Preliminary system beta-testing for safety and efficacy was performed for one year in an open study of 204 patients derived from two independent , health-care environments . Among the two testing centres , over 60,000 telephone cells were received by the computer systems during the start-up year . Safety and efficacy expectations were met . In addition , prevalence of diabetes related crises ( hyperglycaemia or hypoglycaemia ) fell approximately 3-fold . Glycated haemoglobin fell significantly ( 1.0 - 1.3 % ) in patients actively using the system . In control groups of patients not actively using the system , there were no improvements in metabolic control while body weights were stable in all groups . The new system was safe and effective in our h and s and empowered our health professionals to provide improved diabetes care", "Abstract Objective : To determine whether locally developed guidelines on asthma and diabetes disseminated through practice based education improve quality of care in non-training , inner city general practice s. Design : R and omised controlled trial with each practice receiving one set of guidelines but providing data on the management of both conditions . Subjects:24 inner city , non-training general practice s. Setting : East London . Main outcome measures : Recording of key variables in patient records ( asthma : peak flow rate , review of inhaler technique , review of asthma symptoms , prophylaxis , occupation , and smoking habit ; diabetes : blood glucose concentration , glycaemic control , funduscopy , feet examination , weight , and smoking habit ) ; size of practice disease registers ; prescribing in asthma ; and use of structured consultation “ prompts . ” Results : In practice s receiving diabetes guidelines , significant improvements in recording were seen for all seven diabetes variables . Both groups of practice s showed improved recording of review of inhaler technique , smoking habit , and review of asthma symptoms . In practice s receiving asthma guidelines , further improvement was seen only in recording of review of inhaler technique and quality of prescribing in asthma . Sizes of disease registers were unchanged . The use of structured prompts was associated with improved recording of four of seven variables on diabetes and all six variables on asthma . Conclusions : Local guidelines disseminated via practice based education improve the management of diabetes and possibly of asthma in inner city , non-training practice s. The use of simple prompts may enhance this improvement", "OBJECTIVE To evaluate the influence of podiatrist activities on the outpatient care of diabetic patients in terms of knowledge of diabetic foot care , self-care , and minor foot problems . RESEARCH DESIGN AND METHODS There were 733 patients , aged 10–79 years , identified from the national diabetes register . Patients without recent visits to a podiatrist and without an obvious need for foot care were r and omized into a podiatric care group ( education and primary prevention measures , n = 267 ) and a control group ( written instructions only , n = 263 ) . The patients were examined by an independent study podiatrist at baseline and after 1 year . RESULTS Patients in the podiatrist group had greater improvement in knowledge of diabetic foot care ( P = 0.004 ) and self-care ( P The prevalence of callosities in regions other than the calcaneal region decreased more ( P = 0.009 ) in the podiatrist group ( from 54.5 to 39.5 % ) than in the control group ( from 51.3 to 48.2 % ) , and the size of the callosities decreased more ( P the prevalence of callosities was associated with younger age ( Education and primary preventive measures provided individually by a podiatrist result in significant improvements in knowledge and foot self-care scores and in improvements in the prevalence of some minor foot problems . Long-term studies are needed to evaluate whether the intervention of podiatrists starting at an early phase would lead to a reduction in major foot problems", "Disease-specific st and ards for directing patient management are becoming increasingly important . These st and ards , however , are often not followed because they are not sufficiently integrated into the clinical care setting . In this study we describe the development and evaluation of a Computer-Assisted Management Protocol ( CAMP ) of care guidelines for diabetes mellitus . While other studies have shown improved compliance with rule-based reminders , the CAMP customizes disease-specific care guidelines to individual patients over time . We evaluated the effect of the CAMP on compliance with guidelines in a prospect i ve , r and omized controlled study . The study was performed at a family practice clinic where much of the patient record is maintained electronically on The Medical Record ( TMR ) . The management protocol was developed from st and ards published by the American Diabetes Association . Fifty-eight providers were r and omized to either receive or not receive the CAMP for diabetes . Compliance with st and ards was assessed by chart audits of all encounters with diabetic patients during the study interval . The following conclusion was made : the Computer-Assisted Management Protocol result ed in a statistically significant improvement in compliance with diabetes care st and ards", "A r and omized controlled trial was conducted to compare three forms of diabetes follow-up : ( 1 ) general practitioner care , ( 2 ) a system of care shared between the general practitioner ( GP ) and clinic and ( 3 ) conventional clinic care . Two hundred and six diabetic patients without significant diabetes-related or other medical complications were r and omized to one of these follow-up systems . Metabolic control and blood pressure improved significantly and equally in all three groups ( p final attendance rates were 72 % for shared care compared with only 35 % for GP care and 53 % for clinic care . Data collection rates for shared care were comparable with the clinic group for r and om blood glucose ( 88.9 % vs 95.1 % ) , weight ( 93.5 % vs 98.3 % ) , and blood pressure ( 94.8 % vs 92.7 % ) . Only in the case of glycosylated haemoglobin did shared care have poorer data collection ( 66.0 % vs 98.4 % ) . In all these parameters , except blood pressure , shared care out-performed the GP group . We conclude that with adequate support from and communication with hospital-based diabetes services , GPs are capable of providing care appropriate to the needs of uncomplicated diabetic patients", "OBJECTIVE A controlled trial with 15-month follow-up was conducted in two outpatient clinics to study the effects of using the problem-based learning technique to implement a diabetes clinical practice guideline . RESEARCH DESIGN AND METHODS A total of 144 patients with type 2 diabetes aged 25 - 65 years in two internal medicine outpatient clinics were enrolled in the study . African-Americans and Hispanics made up > 75 % of the patients . Doctors and staff in one of the clinics were trained in the use of a clinical practice guideline based on Staged Diabetes Management . A problem-based learning educational program was instituted to reach consensus on a stepped intensification scheme for glycemic control and to determine the st and ards of care used in the clinic . HbA1c was obtained at baseline and at 9 and 15 months after enrollment . RESULTS At 9 months , there was a mean -0.90 % within-subject change in HbA1c in the intervention group , with no significant changes in the control group . The 15-month mean within-subject change in HbA1c of -0.62 % in the intervention group was also significant . Among intervention patients , those with the poorest glycemic control at baseline realized the greatest benefit in improvement of HbA1c . The intervention group also exhibited significant changes in physician adherence with American Diabetes Association st and ards of care . CONCLUSIONS Clinical practice guidelines are an effective way of improving the processes and outcomes of care for patients with diabetes . Problem-based learning is a useful strategy to gain physician support for clinical practice guidelines . More intensive interventions are needed to maintain treatment gains", "The efficacy of quality circles has not yet been evaluated in controlled studies in Germany . The Central Research Institute for Ambulatory Health Care in Germany conducted a prospect i ve controlled trial in order to evaluate the effects of structured quality circles on the process of quality ambulatory care for diabetic patients . Following a training for moderators ( two for each quality circle ) two quality circles undertook five sessions . In a representative r and om sample ( 25 diabetic patients per practice ) , the quality of diabetes care was evaluated before and after participation in the quality circles and was compared to the results of a control group without peer review . The participation in a quality circle result ed in a significant and relevant improvement of the quality concerning the detection of diabetes related complications", "Abstract Objectives : To evaluate integrated care for diabetes in clinical , psychosocial , and economic terms . Design : Pragmatic r and omised trial . Setting : Hospital diabetic clinic and three general practice groups in Grampian . Patients : 274 adult diabetic patients attending a hospital clinic and registered with one of three general practice s. Intervention - R and om allocation to conventional hospital clinic care or integrated care . Integrated care patients seen in general practice every three or four months and in the hospital clinic annually . General practitioners were given written guidelines for integrated care . Main outcome measures : Metabolic control , psychosocial status , knowledge of diabetes , beliefs about control of diabetes , satisfaction with treatment , disruption of normal activities , numbers of consultations and admissions , frequency of metabolic monitoring , costs to patients and NHS . Results - A higher proportion of patients defaulted from conventional care ( 14 ( 10 % ) ) than from integrated care ( 4 ( 3 % ) , 95 % confidence interval of difference 2 % to 13 % ) . After two years no significant differences were found between the groups in metabolic control , psychosocial status , knowledge , beliefs about control , satisfaction with treatment , unscheduled admissions , or disruption of normal activities . Integrated care was as effective for insulin dependent as non-insulin dependent patients . Patients in integrated care had more visits and higher frequencies of examination . Costs to patients were lower in integrated care ( mean pounds sterling 1.70 ) than in conventional care ( pounds sterling 8) . 88 % of patients who experienced integrated care wished to continue with it . Conclusions : This model of integrated care for diabetes was at least as effective as conventional hospital clinic care", "A diabetes protocol characterized by self-monitoring of blood glucose was introduced in four general practice s with the aim of making the frequency of consultations dependent on the metabolic regulation and emphasizing body weight reduction . The feasibility of the programme was investigated and the results after 1 year were compared with those of conventional care in four control practice s. In the experimental practice s , 13 patients switched from a medical specialist 's to a general practitioner 's supervision , 20 remained under supervision of their GP and 33 started self-monitoring . The self-monitoring rate , the consultation frequency according to protocol , the low number of dropouts and inadequate referrals and adherence to the therapeutic scheme showed that the protocol was feasible for both the GPs and the patients . At the initial assessment , the regulation of the diabetes was worse in patients of the experimental group , compared with those of the control group ( mean HbA1 9.7 % vs 8.9 % ; p less than 0.05 ) . On average , patients in the experimental group ( n = 56 ) lost 0.4 kg of body weight , whereas those in the control group ( n = 73 ) gained 0.1 kg ( n.s . ) . The mean change in HbA1 , adjusted for the initial value , was -0.4 % in the experimental and + 0.5 % in the control group ( p less than 0.05 ) . The results of the protocol can be attributed to a combination of greater participation of the patient , the individualized consultation frequency and the prescription of oral hypoglycaemic agents according to body weight development", "OBJECTIVE --To evaluate the effectiveness and acceptability of central ly organised prompting for coordinating community care of non-insulin dependent diabetic patients . DESIGN --R and omised single centre trial . Patients allocated to prompted care in the community or to continued attendance at hospital diabetic clinic ( controls ) . Median follow up two years . SETTING --Two hospital outpatient clinics , 38 general practice s , and 11 optometrists in the catchment area of a district general hospital in Islington . PATIENTS --181 patients attending hospital outpatient clinics . NULL HYPOTHESIS -- There is no difference in process of medical care measures and medical outcome between prompted community care and hospital clinic care . RESULTS --14 hospital patients failed to receive a single review in the clinic as compared with three patients in the prompted group ( chi 2 = 6.1 , df = 1 ; p = 0.013 ) . Follow up for retinal screening was better in prompted patients than in controls ; two prompted patients defaulted as against 12 controls ( chi 2 = 6.9 , df = 1 ; p = 0.008 ) . Three measures per patient yearly were more frequent in prompted patients : tests for albuminuria ( median 3.0 v 2.3 ; p = 0.03 ) , plasma glucose estimations ( 3.1 v 2.5 ; p = 0.003 ) , and glycated haemoglobin estimations ( 2.4 v 0.9 ; p Continuity of care was better in the prompted group ( 3.2 v 2.2 review s by each doctor seen ; p plasma glucose concentration , glycated haemoglobin value , numbers admitted to hospital for a diabetes related reason , and number of deaths . Question naires revealed a high level of patient , general practitioner , and optometrist satisfaction . CONCLUSIONS --Six monthly prompting of non-insulin treated diabetic patients for care by inner city general practitioners and by optometrists is effective and acceptable", "OBJECTIVE To evaluate the effectiveness of a cluster visit model led by a diabetes nurse educator for delivering outpatient care management to adult patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS This study involved a r and omized controlled trial among patients of Kaiser Permanente 's Pleasanton , CA , center who were aged 16 - 75 years and had either poor glycemic control ( HbA1c > 8.5 % ) or no HbA1c test performed during the previous year . Intervention subjects received multidisciplinary outpatient diabetes care management delivered by a diabetes nurse educator , a psychologist , a nutritionist , and a pharmacist in cluster visit setting s of 10 - 18 patients /month for 6 months . Outcomes included change ( from baseline ) in HbA1c levels ; self-reported changes in self-care practice s , self-efficacy , and satisfaction ; and utilization of inpatient and outpatient health care . RESULTS After the intervention , HbA1c levels declined by 1.3 % in the intervention subjects versus 0.2 % in the control subjects ( P self-care practice s and several measures of self-efficacy improved significantly in the intervention group . Satisfaction with the program was high . Both hospital ( P = 0.04 ) and outpatient ( P adults with diabetes improved glycemic control , self-efficacy , and patient satisfaction and result ed in a reduction in health care utilization after the program", "Patients who fail to show for scheduled visits or who fail to contact their provider when warning symptoms occur pose important problems for the primary care physician . A group of interventions was examined to determine the effectiveness in increasing the number of prescribed office visits in patients with diabetes mellitus . This group of interventions included mailed packets with information on how to use the clinic , providers ' names and phone numbers , after-hours phone numbers , a list of early warning signs , and a booklet on managing diabetes mellitus ; mailed appointment reminders ; and intense followup of visit failures for prompt rescheduling . Eight hundred fifty-nine patients on drug therapy for diabetes mellitus were stratified by risk of hospitalization and r and omly assigned within strata to control and intervention groups . The intervention group received all interventions . After 1 year , the intervention group averaged 12 % more total contacts than the control group ( 5.8 vs. 5.2 , P = 0.01 ) , due largely to an increase in kept scheduled visits ( 4.1 vs. 3.6 , P = 0.006 ) . These effects were greatest in those patients at higher risk of hospitalization . Also , visit failures were reduced only in high-risk patients . The effect of the interventions did not diminish during the year of study . This systematic and repetitive intervention appears effective in increasing prescribed office visits and is especially effective in patients requiring more frequent care", "Summary Blood glucose values close to normal reduce the microvascular complications of insulin-dependent diabetes mellitus . The Stockholm study of this effect continued after the initial 7.5-year period in order to see what happened when intensively treated patients were left to control their own treatment while treatment was intensified in the control group . Forty-three patients with insulin-dependent diabetes r and omised to intensified conventional treatment ( ICT ) and 48 patients r and omised to st and ard treatment ( ST ) were followed-up for 10 years . Vascular complications , treatment side-effects and well-being were studied . Risk factors for complications were sought . HbA1c ( normal range 3.9–5.7 % ) was reduced from 9.5 ± 1.4 % ( mean ± SD ) in the ICT group and 9.4 ± 1.2 % in the ST group to a mean ( during 10 years ) of 7.2 ± 0.6 % and 8.3 ± 1.0 % , respectively ( p . Serious retinopathy ( 63 vs 33 % , p = 0.003 ) , nephropathy ( 26 vs 7 % , p = 0.012 ) and symptoms of neuropathy ( 32 vs 14 % , p = 0.041 ) were more common in the ST group after 10 years . HbA1c and age were the only risk factors for complications . Self-reported well-being increased to a greater degree and severe hypoglycaemia was more common in the ICT group . Cognitive function after 10 years was similar in both treatment groups , and was not related to the number of severe hypoglycaemic episodes . Intensified insulin treatment leads to reduced long-term complications and increased well-being without causing undue side-effects . [ Diabetologia ( 1996 ) 39 : 1483–1488", "The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purpose d design diabetes centre , on diabetes control , attendance and cancellation rates , and admission for diabetic emergencies have been review ed . Glycaemic control was examined in : ( a ) a cohort of 163 insulin-treated and 47 non-insulin treated diabetic subjects ( age studied prospect ively before and 3 years following the introduction of a new system of care ; ( b ) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over ; ( c ) a cross-sectional study of the clinic population ( n = 700 ) the year before and 3 years after the changeover ; ( d ) a group of patients attending st and ard unaltered clinics in the same district ( n = 157 ) . Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre , with the means for those aged less than 65 falling from 11.9 + /- 2.3 % to 9.9 + /- 1.9 % and for those aged over 65 from a mean of 11.7 + /- 2.0 % to 10.3 + /- 2.3 % , 3 years later . The cross-sectional study provided similar results with a mean HbA1 of 12.2 + /- 3.0 % prior to changeover and 10.4 + /- 4.4 % , 3 years later . Smaller but significant changes were observed in patients continuing to attend the routine clinic ( from 12.2 + /- 2.3 % to 11.3 + /- 2.6 % ) over a similar period . Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23 , to 33 and 5 per annum , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS", "PURPOSE Clinical guidelines are design ed to assist in the management of specific diseases ; however , these guidelines are often neglected in the delivery of care . The purpose of this study was to determine whether clinician use of an clinical practice guideline would increase in response to having , at the patient visit , a decision support system based on a practice guideline that generates a customized management protocol for the individual patient using data from the patient 's electronic medical record . SUBJECTS AND METHODS In a 6-month controlled trial at a primary care clinic , 58 primary care clinicians were r and omized to receive either a special encounter form with the computer-generated guideline recommendations or a st and ard encounter form . The effect of computer-generated advice on clinician behavior was measured as rate of compliance with guideline recommendations . Data from 30 clinicians were analyzed ; data from 28 clinicians were excluded because these clinicians did not meet predefined criteria for minimum exposure to diabetic patient care . RESULTS Availability of patient management recommendations generated by the decision support system result ed in a two-fold increase in clinician compliance with care guidelines for diabetes mellitus ( P = 0.01 ) . Median compliance for the group receiving the recommendations was 32.0 % versus 15.6 % for the control group . CONCLUSION Decision support based on a clinical practice guideline is an effective tool for assisting clinicians in the management of diabetic patients . This decision support system provides a model for how a clinical practice guideline can be integrated into the care process by computer to assist clinicians in managing a specific disease through helping them comply with care st and ards . Use of decision support systems based on clinical practice guidelines could ultimately improve the quality of medical care", "The purpose of this study was to evaluate the effrcacy of using a telecommunication system to assist in the outpatient management of pediatric patients with insulin- dependent diabetes . Metabolic control , patients ' psychosocial status , family functioning , perceived quality of life , patterns of parental/child responsibility for daily diabetes maintenance , and nursing time-on-task were evaluated . One hundred six pediatric patients ( mean age= 13.3 years ) were r and omly assigned to an experimental or control outpatient clinic for 1 year . Experimental subjects transmitted self-monitoring blood glucose data by modem to the hospital every 2 weeks . Transmitted data were review ed by nurse practitioners who telephoned subjects to discuss regimen adjustments . Control subjects received st and ard care with regimen adjustments made by physicians . There were no significant between-group differences for metabolic control , rates of hospitalization or emergency-room visits , psychological status , general family functioning , quality of life , or parent-child responsibility . A significant decrease was noted in nursing time-on-task for experimental subjects", "The efficacy of a treatment and teaching programme for non-insulin-treated Type 2 diabetic patients in general practice was evaluated in a prospect i ve , controlled study . In a rural area in southern Austria , 53 patients from seven general practice s participated in a structured programme ( intervention group ) and 55 patients from seven general practice s without the programme served as the control group . After 6 months the weight reduction in the intervention group was 2.6 kg ( 1.6 - 3.7 kg , p HbA1c between the groups was 0.92 % ( 0.23 - 1.61 % , p Systolic ( -16.6 mmHg ) and diastolic ( -11.1 mmHg ) blood pressure , serum triglycerides ( -0.63 mmol I-1 ) , and serum cholesterol ( -0.40 mmol I-1 ) were reduced significantly in the intervention group ( p number of patients with callus formation and poor nail care decreased significantly after participating in the teaching programme ( p reduction in body weight , metabolic control or in risk factors for diabetic foot complications were observed . Calculated health care costs per patient and year decreased in the intervention group ( -33 pounds ) and increased in the control group ( + 30 pounds ) mainly due to changes in prescription of oral hypoglycaemic agents in both groups . This programme may be an efficient and helpful model to increase overall quality of diabetes care according to the St Vincent Declaration", "OBJECTIVE To examine baseline renal screening practice s and the effect of nurse case management of patients with diabetes in a group model health maintenance organization ( HMO ) . RESEARCH DESIGN AND METHODS We performed both 1-year retrospective and 1-year prospect i ve studies of renal assessment practice s and ACE inhibitor usage in a cohort of 133 diabetic patients enrolled in a r and omized controlled trial of a diabetes nurse case management program in a group model HMO . In accordance with American Diabetes Association recommendations , urine dipstick and quantitative protein and microalbuminuria testing rates were calculated . RESULTS At baseline , 77 % of patients were screened for proteinuria with dipsticks or had quantitative urine testing . Of patients with negative dipstick findings , 30 % had appropriate quantitative protein or microalbumin follow-up at baseline . Baseline ACE inhibitor usage was associated with decreased follow-up testing ( relative risk = 0.47 ) . Nurse case management was associated with increased quantitative protein or or microalbumin testing and increased follow-up testing ( relative risk = 1.65 and 1.60 , respectively ) . CONCLUSIONS We found a higher degree of adherence to recommendations for renal testing than has been reported previously . Nurse case management intervention further increased renal screening rates . The inverse association between ACE inhibitor usage and microalbumin testing highlights a potentially ambiguous area of current clinical pathways", "Computerized reminder systems have been shown to be effective in improving physician compliance with preventive services guidelines . Very little has been published about the use of computerized reminders for preventive care in diabetes . We implemented a computer-generated reminder system for diabetes care guidelines in a r and omized controlled study in the outpatient clinics of 35 internal medicine residents at the University of Utah and Salt Lake Veterans Affairs Hospitals . After a six month study period , compliance with the recommended care significantly improved in both the intervention group that received patient-specific reminders about the guidelines ( 38.0 % at baseline , 54.9 % at follow-up ) and the control group that received a nonspecific report ( 34.6 % at baseline , 51.0 % at follow-up ) . There was no significant difference between the two groups . Both clinic sites showed similar improvement over baseline levels of compliance . Residents who completed encounter forms used by the system showed a significantly greater improvement in compliance than those who did not complete encounter forms ( 19.7 % vs. 7.6 % , p = 0.006 ) . The improvements in guideline compliance were seen in all areas of diabetes preventive care studied , and significant improvements were seen with recommended items from the medical history , physical exam , laboratory testing , referrals , and patient education . The use of encounter forms by the providers significantly improved documented compliance with the guidelines in almost all categories of preventive care . These results suggest that computerized reminder systems improve compliance with recommended care more by facilitating the documentation of clinical findings and the ordering of recommended procedures than by providing the clinician with patient-specific information about guideline compliance status . Further study is needed to underst and the implication s of these findings to the development of future computerized reminder systems for chronic diseases such as diabetes", "The Swedish National Board of Health and Welfare published its first diabetes health-care program in 1977 . The impact of the program was evaluated in the Stockholm County after 4 yr . The results showed that the educational program had reached ≥1 staff member in 86 % of the 104 primary health-care centers ( PHCCs ) . Several organizational changes had taken place as a result of the program . The 10 “ best ” PHCCs were compared with a r and om sample of the centers with regard to patient outcomes . Patients from the 10 best centers had gotten a more comprehensive education , were more knowledgeable about foot care , tested glucose more often , and used less medication . The metabolic control was the same for both groups of patients . The PHCC staffs reported the following roadblocks to change : lack of knowledge of diabetes care , insufficient cooperation between staff members , poor contact with specialists , and absence of guidelines for diabetes care . The staffs in the best centers spent twice as much time in staff meetings and continuing education as those from the r and om sample of centers . The findings led us to formulate a new strategy for the program . The main objective of the new approach is to create organizational changes within the centers . Thus , local knowledge and creativity can be utilized . Preliminary data demonstrate that 84 % of the locally developed plans for reorganization of diabetes care had been accomplished within 1 yr", "OBJECTIVE To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes . DESIGN Pragmatic parallel group design , with r and omisation between practice teams to routine care ( comparison group ) or routine care plus additional training ( intervention group ) ; analysis at one year , allowing for practice effects and stratifiers ; self reporting by patients on communication with practitioners , satisfaction with treatment , style of care , and lifestyle . SETTING 41 practice s ( 21 in intervention group , 20 in comparison group ) in a health region in southern Engl and . SUBJECTS 250/360 patients ( aged 30 - 70 years ) diagnosed with type 2 diabetes and completing follow up at one year ( 142 in intervention group , 108 in comparison group ) . INTERVENTION 1.5 days ' group training for the doctors and nurses-introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions . MAIN OUTCOME MEASURES Quality of life , wellbeing , haemoglobin A1c and lipid concentrations , blood pressure , body mass index ( kg/m2 ) . RESULTS Compared with patients in the C group , those in the intervention group reported better communication with the doctors ( odds ratio 2.8 ; 95 % confidence interval 1.8 to 4.3 ) and greater treatment satisfaction ( 1.6 ; 1.1 to 2.5 ) and wellbeing ( difference in means ( d ) 2.8 ; 0.4 to 5.2 ) . However , their body mass index was significantly higher ( d=2.0 ; 0.3 to 3.8 ) , as were triglyceride concentrations ( d=0.4 mmol/l ; 0.07 to 0.73 mmol/l ) , whereas knowledge scores were lower ( d=-2.74 ; -0.23 to -5.25 ) . Differences in lifestyle and glycaemic control were not significant . CONCLUSIONS The findings suggest greater attention to the consultation process than to preventive care among trained practitioners ; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management", "Abstract Objectives : To monitor incidence of insulin dependent diabetes in children in Oxford health region since 1985 , and to look for any evidence of disproportionate increase in children aged under 5 . Design : Primary ascertainment of cases of childhood diabetes was by prospect i ve registration of all patients with insulin dependent diabetes diagnosed before age 15 years between 1985 and 1996 and resident in Oxford region at time of diagnosis . This was supplemented by examination of central ised hospital discharge records and death certificates . Secondary case ascertainment was by postal surveys of general practitioners in 1987 and 1996 . Setting : Area formerly administered by Oxford Regional Health Authority . Subjects : 1037 children presenting with insulin dependent diabetes under age of 15 years . Main outcome measures : Incidence of insulin dependent diabetes in children aged 0 - 4 , 5 - 9 , and 10 - 14 years during 1985 - 95 . Results : Overall incidence of diabetes in children aged 0 - 15 was 18.6 cases/100 000/year and showed an annual increase of 4 % from 1985 to 1996 . This was mainly due to a rapid increase in children aged 0 - 4 years , in whom there was an annual increase of 11 % ( 95 % confidence interval 6 % to 15 % , P Incidence of insulin dependent diabetes in children aged under 5 years has risen markedly in the Oxford region over the past decade . The cause of the increase is unknown , but environmental influences encountered before birth or in early postnatal life are likely to be responsible . Key messages The incidence of childhood diabetes has increased in Europe and many other parts of the world over the past 20 - 30 years In the Oxford region we found that the incidence of childhood insulin dependent diabetes increased by 4 % per year during 1985 - 95 Most of this increase was due to an increase of 11 % a year in children aged under 5 years , in whom incidence doubled over the study period Environmental factors encountered very early in life are likely to have been responsible for this increase , but the nature of such factors is unknown Attempts at preventing disease should be directed towards intrauterine or early postnatal", "The Diabetes Control and Complications Trial ( DCCT ) and the Kumamoto study [ 1 , 2 ] showed that near-normal glycemic control reduces the development and progression of microvascular and neuropathic complications by approximately 50 % in type 1 and type 2 diabetes mellitus . Additional analyses [ 3 - 5 ] indicate that therapy to achieve near normalization of blood glucose levels is cost-effective compared with other treatments . Thus , the American Diabetes Association has recommended that all persons with diabetes attempt to achieve near normalization of blood glucose levels [ 6 ] . This recommendation is not routinely followed in medical practice . In a 1989 national survey of physician practice behaviors in the United States , 64 % of physicians agreed that achieving target HbA1c values is very important but only 18 % reported that they ordered HbA1c tests every 2 to 3 months for patients with type 1 diabetes [ 7 ] . Although 98 % agreed that patient education improves glucose control , only 55 % reported that they routinely used a dietitian or a diabetes educator in patient care . Studies indicate that bringing clinical practice into line with scientific knowledge can be difficult . Methods used to achieve diabetes control in clinical trials are re source intensive . The American Diabetes Association currently recommends that patients with diabetes see their primary care physicians two to four times per year . Data from the National Health Interview Survey , a nationally representative survey [ 8 ] , indicate that most patients with diabetes are seen by nonspecialists and that 69 % of physician visits last less than 15 minutes . Algorithms for diabetes care exist but may be complex and difficult for physicians to follow , given patient load , diversity of patients seen , lack of information systems , and time constraints . Simple , low-cost methods of translating guidelines into clinical care are required . One solution may be to make greater use of personnel other than physicians . Nurse case management was an integral part of intensive therapy in the DCCT and has proven to be effective in reducing smoking and cholesterol levels after acute myocardial infa rct ion [ 3 , 9 ] . A nonr and omized study [ 10 ] of more than 700 patients with diabetes in a health maintenance organization suggests that nurse case management may be effective in improving metabolic control . Other studies [ 11 , 12 ] show a strong association between algorithm-directed nurse interventions and improved glycemic control . To our knowledge , no r and omized , controlled clinical trial of nurse case management in diabetes has yet been published . In a 12-month r and omized , controlled trial , we compared a nurse case management model of diabetes care with usual diabetes management in a primary care setting . Methods Patients Our study was approved by the institutional review board of the Prudential Center for Health Care Research , and all patients gave written informed consent . Participants were recruited from two of the largest clinics within the Jacksonville Health Care Group , which is the largest provider of primary care services for the Prudential HealthCare HMO plan of Jacksonville , Florida . The Jacksonville Health Care Group is a group of 43 primary care physicians who provide care in eight clinics to more than 75 000 Prudential HealthCare plan members . Potential study participants were identified through a data base used to support quality -improvement activities . Prudential HealthCare HMO members who had diabetes were included in the data base if they had visited a physician for diabetes ( International Classification of Diseases , 9th Revision , codes 250.0 to 250.9 ) , had had a hospital cl aim processed for diabetes , had been seen by the utilization management nurse , or had been referred to an ophthalmologist for a diabetic retinal examination . This data base is up date d regularly . A list with each member 's name , address , telephone number , medical record number , member identification number , age , sex , physician , and clinic was generated by merging the data from the data base with enrollment information . In addition , a list of members who may have had diabetes was created by using pharmacy data . Adult members with diabetes who were potential study participants each received a recruitment call and were invited to schedule an appointment with a research assistant to discuss participation in the study . We made a total of 14 calls at different times and on different days before coding a member as unavailable . After consent was given and the eligibility assessment was completed , baseline information was obtained and an HbA1c test was ordered if the result of one given within the previous 60 days was not available . Patients were ineligible for the study if they had a recent HbA1c value less than 7.0 % ; had uncontrolled hypertension ( blood pressure > 180/110 mm Hg ) ; had unstable angina ( class 4 ) ; had had a myocardial infa rct ion in the past 3 months ; had had two or more episodes of seizures ; had alcoholism or drug abuse documented in the chart ; had late-stage complications of diabetes or other chronic conditions , such as severe immunodeficiency or cirrhosis ; were pregnant or were planning to become pregnant in the next 12 months ; or were unable to perform self-management . Patients were r and omly assigned in blocks to either the nurse case management ( intervention ) group or the usual care group . R and omization was based on a 1:1 allocation ratio and a block size of three . Each block contained six patients , three in each study group . This r and omization scheme ensured that the desired allocation ratio-one intervention patient to one usual care patient-was maintained after sequential enrollment of every sixth patient . Outcome Measures Change in HbA1c value was the primary outcome measure . Decreased HbA1c values correlate directly with reduced risk for diabetes-related microvascular and neuropathic complications in type 1 and type 2 diabetes [ 1 , 3 ] . We also assessed health-related quality of life by using four generic questions developed by the Centers for Disease Control and Prevention for the Behavioral Risk Factor Surveillance System ( BRFSS ) [ 13 , 14 ] . These questions evaluate key conceptual domains of health-related quality of life : 1 ) patient-perceived general health status , 2 ) patient-perceived physical dysfunction during the previous 30 days , 3 ) patient-perceived mental dysfunction during the previous 30 days , and 4 ) patient-perceived functional incapacity during the previous 30 days for either mental or physical reasons . The BRFSS quality -of-life measures have been vali date d in a national sample of adults in the United States [ 15 ] . Patient-perceived health was found to be a good proxy indicator for chronic disease conditions . The other three domains further characterize general health functioning and quality of life [ 15 ] . In this analysis , we report findings related to the patient-perceived general health status domain . Intervention and Follow-up The nurse case manager was a registered nurse and a certified diabetes educator . She was trained to follow a set of detailed management algorithms under the direction of a board-certified family medicine physician and an endocrinologist who were responsible for all diabetes management decisions for patients in the intervention group but were not primary care providers for these patients . The algorithms were specific for type of diabetes and were developed by a multidisciplinary team on which endocrinology , family medicine , nursing , pharmacy , health services research , and epidemiology were represented . The algorithms progressively moved a patient toward improvement of glycemic control through adjustments in medication , meal planning , and reinforcement of exercise ( Figure 1 ) . Figure 1 . Algorithm for management of type 2 diabetes mellitus . Patients assigned to receive nurse case management met with the nurse for an initial assessment , were instructed about a blood glucose monitoring schedule , and returned for a follow-up visit 2 weeks later . The initial visit with the nurse averaged 45 minutes . At the 2-week follow-up visit , the nurse review ed the patient 's blood glucose log ; explained the algorithm step to which the patient had been assigned ; and used this information as the baseline for subsequent medication adjustments , meal planning , and exercise reinforcement . Patients receiving nurse case management were also referred to a 5-week , 12-hour diabetes education program that included individual counseling by a dietitian , individual counseling by an exercise therapist , and group diabetes education classes . Subsequent in-person follow-up visits occurred quarterly . Patients in the nurse case management group who were taking insulin received weekly follow-up telephone calls . After the nurse review ed the blood glucose log and discussed glucose values with the patient , medication regimens were adjusted as needed and meal planning and exercise were reinforced . Patients treated with oral agents or diet and exercise received follow-up telephone calls every 2 weeks . The nurse case manager met at least biweekly with the family medicine physician and the endocrinologist to review patient progress , medication adjustments , and other issues related to diabetes care . All medication adjustments or changes were communicated to the patients ' regular primary care physicians . Patients assigned to receive usual care were given blood glucose meters and strips , were encouraged to discuss enrollment in the diabetes education class with their physicians if they had not done so in the past year , and continued to receive diabetes care and follow-up from their primary care physicians . The 5-week diabetes education program is a st and ard , free-of-charge benefit for all HMO members with diabetes . All Jacksonville Health Care Group primary care physicians participate in an annual diabetes care seminar and undergo regular peer review of their adherence to published diabetes care st and ards . Tests to", "BACKGROUND While lower-extremity amputation ( LEA ) is a frequent complication of diabetes , effective strategies for the prevention of LEA in primary care setting s have not been extensively studied . METHODS This prospect i ve study of American Indians with diabetes in a rural primary care clinic was divided into three periods : the st and ard care period ( 1986 to 1989 ) , during which patients received foot care at the discretion of the primary care provider ; the public health period ( 1990 to 1993 ) , during which patients were screened for foot problems and high-risk individuals received foot care education and protective footwear ; and the Staged Diabetes Management ( SDM ) period ( 1994 to 1996 ) , during which comprehensive guidelines for diabetic foot management were adapted by the primary care clinicians to their practice s and were systematic ally implemented . RESULTS A total of 639 individuals contributed 4322 diabetic person-years during the three periods of observation . Patient sex distribution , mean age , and mean duration of diabetes were similar i the three periods . The average annual LEA incidence was 29/1000 diabetic person-years for the st and ard care period ( n = 42 ) , 21/1000 for the public health period ( n = 33 ) , and 15/1000 for the SDM period ( n = 20 ) , an overall 48 % reduction ( P = .016 ) . Overall , the incidence of a first amputation declined from 21/1000 to 6/1000 ( P practice guidelines by local primary care providers was associated with improved diabetic foot care outcomes . SDM has relevance to primary care organizations seeking to improve outcomes for patients with diabetes", "The Nederl and s Huisartsen Genootschap ( NHG ) , the college of general practitioners in the Netherl and s , has begun a national programme of st and ard setting for the quality of care in general practice . When the st and ards have been drawn up and assessed they are disseminated via the journal Huisarts en Wetenschap . In a survey , carried out among a r and omized sample of 10 % of all general practitioners , attitudes towards national st and ard setting in general and to the first set of st and ards ( diabetes care ) were studied . The response was 70 % ( 453 doctors ) . A majority of the respondents said they were well informed about the national st and ard setting initiatives instigated by the NHG ( 71 % ) and about the content of the first st and ards ( 77 % ) . The general practitioners had a positive attitude towards the setting of national st and ards for quality of care , and this was particularly true for doctors who were members of the NHG . Although a large majority of doctors said they agreed with most of the guidelines in the diabetes st and ards fewer respondents were actually working to the guidelines and some of the st and ards are certain to meet with a lot of resistance . A better knowledge of the st and ards and a more positive attitude to the process of national st and ard setting correlated with a more positive attitude to the guidelines formulated in the diabetes st and ards . The results could serve as a starting point for an exchange of views about st and ard setting in general practice in other countries", "OBJECTIVE To determine the extent of functional impairment among veterans with diabetes and investigate whether such functional impairment is associated with measures of glycemic control , sensory neuropathy , lower extremity macrovascular disease , or other comorbid conditions . RESEARCH DESIGN AND METHODS A 20-item general health survey ( SF-20 ) developed by the Medical Outcomes Study ( MOS ) Group , was administered to 577 subjects participating in a prospect i ve study of risk factors for diabetic foot ulceration . Measures of glycemic control and neurovascular disease included GHb , sensory lower extremity neuropathy assessed by aesthesiometry , and segmental lower extremity doppler blood pressures . RESULTS Veterans with diabetes have major decreases in all domains of functional status ; 87 % were in poor health in terms of physical functioning and 86 % in terms of health perceptions . Those with advancing age , symptoms of neuropathy and claudication , and a medical history of complications associated with diabetes had significantly more impairment of health status than those without . GHb values did not correlate with functional status measures . Subjects with neuropathy had statistically significant functional impairment . Subjects with vasculopathy had only two significantly low health status measures . CONCLUSIONS In summary , the findings from this survey reveal that veterans with diabetes have low functional status scores . The presence of symptoms and complications accounts for only part of the impairments experienced by this group", "OBJECTIVE : To assess the effectiveness of a pharmaceutical care model on the management of non-insulin-dependent diabetes mellitus ( NIDDM ) in urban African-American patients . DESIGN : Eligible patients were r and omized to either a pharmacist intervention or control group and followed over a 4-month period . Patients in the intervention group received diabetes education , medication counseling , instructions on dietary regulation , exercise , and home blood glucose monitoring , and evaluation and adjustment of their hypoglycemic regimen . Patients in the control group continued to receive st and ard medical care provided by their physicians . SETTING : A university-affiliated internal medicine outpatient clinic . PARTICIPANTS : The study population consisted of urban African-American patients with NIDDM currently attending the clinic . MAIN OUTCOME MEASURES : Primary outcome measures included fasting plasma glucose and glycated hemoglobin concentrations . Secondary outcome endpoints included blood pressure , serum creatinine , creatinine clearance , microalbumin to creatinine ratio , total cholesterol , triglycerides , high-density lipoprotein , and low-density lipoprotein concentrations . Quality -of-life assessment s were performed in both groups at baseline and at the end of the study . RESULTS : Thirty-nine patients ( 17 intervention , 22 control ) completed the study . The intervention group consisted of 12 women and 5 men with a mean ± SD age of 59 ± 12 years , total body weight ( TBW ) of 93 ± 22 kg , body mass index ( BMI ) of 34 ± 7 kg/m2 , and duration of NIDDM 6.8 ± 6.5 years . The control group consisted of 15 women and 7 men with a mean age of 65 ± 12 years , TBW of 88 ± 19 kg , BMI of 33 ± 7 kg/m2 , and a duration of NIDDM of 6.2 ± 4.8 y. Significant improvement in glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.015 ) was achieved in the intervention group . No change in glycemia was observed in the control subjects . Statistically significant differences in the final glycated hemoglobin ( p = 0.003 ) and fasting plasma glucose ( p = 0.022 ) concentrations were noted between groups . No significant changes in blood pressure control , lipid profile , renal function parameters , weight , or quality -of-life measures were noted within or between groups . CONCLUSIONS : Our data demonstrate the effectiveness of pharmaceutical care in the reduction of hyperglycemia associated with NIDDM in a group of urban African-American patients", "We conducted a pilot r and omised trial of computerised templates for the management of asthma and diabetes in general practice in six general practice s in North London . Uptake of the guidelines by general practitioners and practice nurses was assessed using qualitative ( semi-structured interviews design ed to assess the users ' views ) and quantitative ( change in use of the template during the study period ) outcome measures . The practice nurses used the templates frequently but general practitioners rarely used them . Several reasons were offered for non-use of the templates , such as the length of the template and non-involvement in the care of asthma or diabetes . Despite this , however , health professionals were favourably disposed to the use of templates for general clinical care . Pilot investigations of computerised templates are best achieved by observational or quasi-experimental methods rather than a r and omised controlled trial . The use of both qualitative and quantitative methods in this study allowed exploration of the barriers to use of computers", "A functional interpretation of clinical pharmacy as an implementing mechanism for extending the objectives and responsibilities of clinical pharmacology in ambulatory patient care is presented . Evidence is given to support the effectiveness of the clinical pharmacist in assisting primary care physicians with the design of optimal drug regimens and evaluating and managing patients on chronic drug therapy . Opportunities for the clinical pharmacist to carry out long-term drug trials and participate in the design and execution of epidemiological drug studies are also discussed . The clinical pharmacist can make important contributions to ambulatory patient care in areas of drug treatment and evaluation by working in concert with primary care physicians and clinical pharmacologists", "To examine the effects of intensive patient and /or physician diabetes education on patient health outcomes , a controlled trial was conducted in which internal medicine residents and their 532 diabetic patients were r and omly assigned to : routine care ; patient education ; physician education ; or both patient and physician education . Patient outcome data were analyzed either by analysis of covariance on post intervention values ( 2-hour post-pr and ial plasma glucose [ PPG ] ; body weight [ BW ] ; blood pressure [ BP ] ; or analysis of variance conducted on change values ( fasting plasma glucose [ FPG ] and glycosylated hemoglobin [ A1Hgb ] ) . After patient education , significant improvements were observed in FPG , A1Hgb , BW , and systolic and diastolic BP . Physician education result ed in significant decreases in FPG , A1Hgb and BW . The combination of patient plus physician education result ed in the greatest improvements in patients ' health outcomes including FPG , A1Hgb , PPG , BW and diastolic BP . Adjusted systolic BPs were not significantly different in the two groups . While these physiologic improvements were statistically and probably clinical ly significant , hyperglycemia and obesity still persisted . Thus , achieving optimal patient outcomes for a chronic disease like diabetes mellitus may require a greater or more effective use of re sources than currently estimated", "Given that 14 million Americans have diabetes [ 1 ] , the common complications of this disorder , such as foot ulcers and lower extremity amputations , are of major concern to the medical community . Approximately 20 % of all diabetic patients hospitalized in the United States are admitted because of foot complications [ 2 , 3 ] . Furthermore , about 50 % of all nontraumatic amputations in the United States are done in patients with diabetes [ 1 , 4 ] . This proportion equates to about 55 000 amputations a year [ 1 ] or 59.7 amputations for every 10 000 persons with diabetes [ 5 ] . Patients who undergo an amputation are at greater risk for a second similar procedure on either the same or the other leg [ 6 , 7 ] . Yet , it has been estimated that about one half of the amputations in patients with diabetes , or about one fourth of the total amputations done in the United States , are preventable [ 1 , 4 ] . Recently , the focus has been on preventive strategies that minimize foot damage in diabetic patients and thereby reduce the rates of ulcers and amputations . These preventive strategies are based on two observations : first , that simple efforts on the part of the health care provider or patient can reduce the likelihood of subsequent amputation due to diabetes-associated foot disease [ 8 ] ; and second , that many of these simple procedures are not being systematic ally applied by health care providers or patients [ 9 ] . For example , studies indicate that physicians infrequently examine the feet of patients with diabetes [ 9 , 10 ] . Also , most patients with diabetes do not engage in simple foot-care assessment s to identify lesions requiring early treatment [ 11 ] . Preventive strategies are not systematic ally applied for several reasons : First , patients may not be aware of foot-care procedures or how to do them , or they may not believe that such procedures can make a difference ; second , podiatry and orthopedics services that could assist in foot salvage in diabetic patients may not be available ; and , finally , the health care system may make it difficult for patients or health care providers to examine the feet of patients with diabetes [ 10 ] . Several uncontrolled studies found that implementation of improved foot-care programs can significantly reduce lower extremity complications in patients with diabetes ; these studies showed a 44 % to 85 % reduction in the rate of lower extremity amputations [ 4 , 12 - 14 ] . A recent casecontrol study also supports the implementation of preventive strategies , such as foot care , use of protective footwear , and aggressive treatment of foot infection by patients or health care providers , to decrease the risk for lower extremity amputation [ 15 ] . The intervention in our study was design ed to reduce the prevalence of risk factors for lower extremity amputations in patients with noninsulin-dependent diabetes and involved the three major elements of a prevention program : the patient , health care providers , and the health care system . Specifically , we did a r and omized , controlled trial to determine whether a comprehensive foot-care intervention could improve patients ' knowledge and performance of appropriate foot care ; increase the number of referrals to specialty clinics such as the podiatry clinic ; increase the frequency of foot examinations by health care providers and the documentation of risk factors in the medical record ; and improve short-term patient outcomes such as skin and nail conditions known to be risk factors for ulcers and amputations . Methods Setting Our study , the design of which is summarized in Figure 1 , was done from April 1989 to March 1991 in the academic general medicine practice of the Regenstrief Health Center in Indianapolis , Indiana [ 16 ] . The practice is subdivided into four primary care teams ( labeled A , B , C , and D ) , each with its own nursing and clerical staff . Each team sees patients for eight half-day sessions per week , with each session staffed by one or two faculty internists and two to four housestaff . Teams A and C were r and omly assigned to the intervention group ; teams B and D were assigned to the control group . Previous studies in which this method of r and omization was used have shown no baseline interteam differences in patient characteristics and physician practice behavior and no effect of the team on the study outcome [ 16 - 19 ] . Figure 1 . Summary of the study design . Patient Identification and Recruitment The computerized Regenstrief Medical Record System [ 20 ] was used to identify approximately 3000 patients with noninsulin-dependent diabetes , as well as the date and time of their next appointment . Only patients with noninsulin-dependent diabetes who were seen at least two times in the preceding year by the same provider were included in the study . Additional criteria for inclusion were as follows : an age greater than 40 years ; a diagnosis of diabetes after 30 years of age ; a diagnosis of diabetes based on National Diabetes Data Group criteria [ 21 ] or the presence of disease requiring medication for the control of hyperglycemia ; an intention to obtain care at the general medicine practice for the next 2 years ; and a body weight that was either ideal or heavier than ideal . Exclusion criteria included pregnancy ; major psychiatric illness , including dementia ; terminal illness likely to cause death within 1 year ; renal failure ( serum creatinine > 440 mol/L ) ; previous bilateral amputations above or below the knee ; or an inability to provide any self-care . Patients of investigators involved in the protocol were also excluded from the study . Of the 728 eligible patients , 244 refused to participate , 89 enrolled in the study but failed to keep their appointments for assessment , and 395 were assessed by trained nurse-clinicians . Of the 395 patients assessed , 352 ( 89 % ) completed the study ; 43 patients ( 11 % ) did not complete the study for the following reasons : death ( 11 patients ) ; change of residence ( 15 patients ) ; illness ( 6 patients ) ; transportation problems ( 3 patients ) ; and miscellaneous reasons ( 8 patients ) . Patient Assessment Sample s for determining fasting plasma glucose , cholesterol , triglyceride , high-density lipoprotein , hemoglobin A1C , and C-peptide levels were obtained from enrolled patients and immediately transported to a certified laboratory for analysis . Patients gave a history and had a physical examination at study entry and approximately 1 year later ( mean , 11.8 1.5 months ) . These examinations focused on risk factors for amputation and were administered by two trained nurse-clinicians who were blinded to the patients ' experimental conditions . Foot-related data derived from the history and physical examination included the patient 's self-reported foot-care behaviors ; the quality of the patient 's examination of his or her feet ; the severity of any foot lesions ; and the presence of musculoskeletal abnormalities , dermatologic conditions , peripheral vascular disease , and peripheral neuropathy ( the neuropathy assessment included quantitative measures of pressure and temperature sensation ) . Patients were question ed about their regular foot-care routine and were asked to show how they examined their feet . During this self-examination , nurse-clinicians observed whether patients ' scrutinized the toenails , the soles of the feet , and the area between toes . Musculoskeletal and dermatologic abnormalities were assessed using st and ard definitions of findings such as callus , hammer toe , and Charcot foot [ 3 , 22 ] . The nurse-clinicians palpated the dorsalis pedis , posterior tibial , and femoral pulses bilaterally in their assessment for peripheral vascular disease . If a pulse was absent at any one of the six sites palpated , the assessment was considered abnormal . Foot lesions were rated for severity using the Seattle Wound Classification System [ 23 ] , which ranges from a grade of 1.1 ( absence of lesions ) to a grade of 10 ( entire foot or leg is gangrenous ) . In our study , a foot lesion was defined as any wound , with or without functional interruption of the protective cutaneous barrier , ranging from a superficial scratch to an ulcer involving the epidermis . A serious foot lesion was defined by a severity grade of at least 1.3 , which indicates a minor , nonulcerated lesion with clinical evidence of healing sufficient to close previous interruption of the cutaneous barrier [ 23 ] or a blister . Pressure and temperature sensations were measured using the 5.07-log ( 0.1 mg)-force Semmes-Weinstein monofilament and the thermal sensitivity testing apparatus , according to st and ard techniques [ 24 - 26 ] . Thermal sensitivity was considered abnormal if the patient had a value greater than 2 st and ard deviations from the mean value for a group of healthy persons without diabetes ( warm > 2.04 C ; cool > 1.58 C ) . Practice Patterns of Health Care Providers Immediately after each scheduled visit , study patients had a structured interview [ 10 ] with a research assistant , who asked about foot self-examination and foot-care education given by health care providers ( the primary care physician or nursing personnel ) . In addition , a chart audit was conducted by a nurse-clinician who was blinded to the patients ' experimental condition . Information abstract ed from the medical record included the physician 's documentation of the findings from the history and physical examination ; any referral to podiatry , orthopedics , or vascular surgery clinics ; and diagnostic-test ordering related to the evaluation and treatment of diabetes-associated foot problems . Intervention The intervention cohort was exposed to several risk-reduction strategies . The nurse-clinicians conducted the patient education session with one to four patients , covering appropriate foot-care behaviors and footwear , using a commercially available slide and audiotape presentation [ 27 ] and pamphlets [ 28 ] . Behavioral contracts regarding desired foot-care behaviors were negotiated with each patient . Follow-up was done by telephone 2 weeks after the education sessions to remind patients", "AIM Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes . METHODS We carried out a r and omized controlled trial within general practice s as the basis for r and omization and a before- and -after design for measures of patient outcome . A parallel process study examined the use of the method by professionals . The study was carried out in 29 general practice s in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care . The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practice s. The main outcome measures were changes in glycosylated haemoglobin , patient satisfaction with care and treatment , functional health status and professional ability to apply the intervention . RESULTS Professionals adopted the innovative method with enthusiasm , but after 2 years only 19 % continued to apply the method systematic ally . The trial was , therefore , unable to demonstrate significant biochemical or functional improvements . This highlights the need to underst and the factors associated with professional uptake and subsequent ability to sustain changes in behaviour . CONCLUSIONS The efficacy of this behavioural intervention remains unproved , despite its acceptability to professional staff . Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on r and omized controlled trials which involve complex behavioural changes in professionals or patients", "Shortages in health care personnel have caused the expansion of nurses * duties . Physician acceptance of this augmented role for the nurse will depend in fact on appropriate studies . Extending the responsibilities of the nurse practitioner to active patient treatment is the basis of this report .", "OBJECTIVE To examine whether a telephone-delivered intervention ( TDI ) , design ed to improve glycemie control in patients with non-insulin-dependent diabetes mellitus ( N1DDM ) , improved coronary risk factors in high-risk patients . RESEARCH DESIGN AND METHODS This r and omized controlled trial involved 275 veterans with N1DDM followed in a general medical clinic . Intervention ( TDI ) patients were telephoned at least monthly by a nurse . Calls emphasized compliance with the medical regimen ( diet , medications , and exercise ) , encouraged behavioral changes , and facilitated referrals to a dietitian or smoking cessation clinic . Control patients received no such calls . Baseline and 12-month follow-up measurements included fasting lipid profiles , weight , smoking status ( self-reported ; cessation verified by measurement of exhaled CO ) , adherence to diet and exercise ( self-reported ) , appointments , and medications ( hospital computerized data base ) . RESULTS After 12 months , equal numbers of obese patients in the two groups reported adhering to a diabetic diet and exercising , although more obese TDI patients had seen a dietitian ( 30 vs. 7 % , P = 0.003 ) . Weight loss was not seen in either group ( —0.9 ± 5.3 vs. —0.1 ± 3.6 kg , P = 0.202 ) . Hyperlipidemic TDI patients were more likely to see a dietitian ( 31 vs. 6 % , P = 0.003 ) and receive lipid-lowering medications ( 22 vs. 9 % , P = 0.096 ) , but serum cholesterol reduction was similar between groups ( –11.7 ± 33.4 vs. –4.3 ± 32.7 mg/dl , P = 0.270 ) ; comparable results were seen for high-density lipoprotein , low-density lipoprotein , and triglyceride levels . More TDI group smokers reported quitting ( 26 vs. 0 % , P = 0.033 ) , but the difference was not significant for CO-verified abstention ( 10 vs. 0 % , P = 0.231 ) . CONCLUSIONS The TDI improved self-reported adherence to regimens that might reduce coronary risk , but had little effect on objective measures of risk", "A crossover r and omized controlled trial of cycles of quality assurance in 16 primary care ( 8 medical , 8 pediatric ) group practice s was conducted . Of four medical and four pediatric tasks important to patient outcome , two were r and omly assigned to experimental intervention ( a quality assurance cycle ) , and two were also measured and used as blinded controls for each medical or pediatric group practice . Task performance was measured in each group for 12 months prior to , 9 months during , and 9 months after the experimental intervention , using as a performance score the percentage of evaluation criteria failed of those applicable to a case . As a result of quality assurance intervention , quality of performance was significantly improved in two of the tasks ( P patient health ( low physician motivation ) had greater improvement in quality . Unimproved tasks were associated with the perceived need for delivery system changes beyond the immediate control of the individual practitioner", "This project tested the importance of enhanced information transfer of home monitoring results to health care providers . The study tested whether computer-assisted communication of medical information between the chronic care patient and the physician can result in health care benefit . The information tools were constructed/adapted as a test of this hypothesis for diabetes mellitus . Patients connected a glucometer to an intelligent modem weekly for six to nine months . Graphical and mathematical tools extracted and emphasized the information content of the home monitoring data arriving at the central site . Data smoothing , trend analysis , and calculation of quality control statistics were incorporated into a graphical time series oriented report that was used by the health care provider during an outpatient visit . The integrated home monitoring system was tested on 20 patients with diabetes in a double cross-over design over a 15-month period . A significant improvement in serum glucose control as measured by glycated hemoglobin was shown in the study group , but not in the control group", "OBJECTIVE To determine whether multiple mailed patient reminders can produce an increase in the rate of diabetic retinal examinations ( DRE ) over that seen with a single reminder . RESEARCH DESIGN AND METHODS All diabetic members > or = 18 years who were enrolled in a large network-based health maintenance organization ( HMO ) in California from August 1996 to July 1997 were identified using cl aims and pharmacy data bases . Members who had no record of DRE in the HMO 's cl aims data base were then r and omized into two groups . Both groups received mailed educational material s and a reminder to obtain the examination . Their physician groups also received a letter explaining the program , current guidelines for DRE , and a list of their diabetes patients with their DRE status . The single intervention group received no additional reminders . The multiple intervention group received additional reminders at 3 , 6 , and 9 months after baseline if they continued with no record of service , as determined from the cl aims data base . RESULTS The study cohort comprised 19,523 diabetic members , which were r and omized into single ( n = 9,614 ) and multiple ( n = 9,909 ) intervention groups . There was an increase in monthly DRE rates after the intervention in August 1996 for both intervention groups . After the second reminder was sent to the multiple intervention group , the percentage of diabetic members receiving DRE was higher than the single intervention group . Rates before and after the third intervention were not significantly different , nor were monthly differences found . There was a significant difference in overall annual DRE rates between the groups ( P = 0.023 ) . CONCLUSIONS Multiple patient reminders are more effective than single reminders in improving DRE rates in a managed care setting . However , the improvement noted was clinical ly small and appeared only after the second reminder ; no incremental improvement was seen with additional reminders . Re sources used for multiple reminders aim ed at diabetic retinopathy might better be spent on other approaches to reducing complications of diabetes" ]	4118338a-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Muscle weakness in old age is associated with physical function decline . Progressive resistance strength training ( PRT ) exercises are design ed to increase strength . OBJECTIVES To assess the effects of PRT on older people and identify adverse events . SEARCH STRATEGY We search ed the Cochrane Bone , Joint and Muscle Trauma Group Specialized Register ( to March 2007 ) , the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2007 , Issue 2 ) , MEDLINE ( 1966 to May 01 , 2008 ) , EMBASE ( 1980 to February 06 2007 ) , CINAHL ( 1982 to July 01 2007 ) and two other electronic data bases . We also search ed reference lists of articles , review ed conference abstract s and contacted authors . SELECTION CRITERIA R and omised controlled trials reporting physical outcomes of PRT for older people were included . DATA COLLECTION AND ANALYSIS Two review authors independently selected trials , assessed trial quality and extracted data . Data were pooled where appropriate . MAIN RESULTS One hundred and twenty one trials with 6700 participants were included . In most trials , PRT was performed two to three times per week and at a high intensity . PRT result ed in a small but significant improvement in physical ability ( 33 trials , 2172 participants ; SMD 0.14 , 95 % CI 0.05 to 0.22 ) . Functional limitation measures also showed improvements : e.g. there was a modest improvement in gait speed ( 24 trials , 1179 participants , MD 0.08 m/s , 95 % CI 0.04 to 0.12 ) ; and a moderate to large effect for getting out of a chair ( 11 trials , 384 participants , SMD -0.94 , 95 % CI -1.49 to -0.38 ) . PRT had a large positive effect on muscle strength ( 73 trials , 3059 participants , SMD 0.84 , 95 % CI 0.67 to 1.00 ) . Participants with osteoarthritis reported a reduction in pain following PRT(6 trials , 503 participants , SMD -0.30 , 95 % CI -0.48 to -0.13 ) . There was no evidence from 10 other trials ( 587 participants ) that PRT had an effect on bodily pain . Adverse events were poorly recorded but adverse events related to musculoskeletal complaints , such as joint pain and muscle soreness , were reported in many of the studies that prospect ively defined and monitored these events . Serious adverse events were rare , and no serious events were reported to be directly related to the exercise programme . AUTHORS ' CONCLUSIONS This review provides evidence that PRT is an effective intervention for improving physical functioning in older people , including improving strength and the performance of some simple and complex activities . However , some caution is needed with transferring these exercises for use with clinical population s because adverse events are not adequately reported	[ "This study examined balance ability , lower-extremity muscle strength , fear of falling and their inter-relationships in 40 community-dwelling older adults ( > 65 years ) . Subjects who self-identified either as being fearful offalling or not ( no concern ) were screened to exclude those with known risk factors for falling . Limits of stability , maximal isometric strength , gait speed , and fear of falling were contrasted between groups ( 27 control subjects , 13 fearful subjects ) . Those fearful of falling demonstrated smaller center of pressure ( COP ) excursions in anterior , left , and right directions ( p used a smaller percentage of their base of support during maximal weight shifting in combined anterior-posterior and right-left directions ( p Strength did not differ between groups , but was associated with the ability to shift the COP in the anterior-posterior direction ( p weight shifting ability ( p Seniors fearful of falling demonstrated limitations in balance ability and balance confidence that could not be explained by muscle weakness", "Periodization is the most effective approach to resistance training ; however , optimal cycle lengths for older persons are not known . This study examined the duration s of performance increments , plateaus , and decrements in women , ages 61 - 75 yr , over 9 wk of isokinetic training . After a 2-wk adaptation cycle , older women trained for either power ( PWR ; 4.73 rad/s ; n = 9 ) or strength ( STR ; 1.05 rad/s ; n = 8) , 3 days/wk with a 1-day recovery between sessions . Repetitions were initially selected to equilibrate work volume between groups . Average power ( AP ) , peak torque ( PT ) , and total work ( TW ) curves were analyzed using forward and backward stepwise regression to ascertain inflections and plateaus . PWR training produced the highest AP , whereas STR produced the highest PT . TW was similar between groups . The AP curves of the PWR group initially showed a steep positive slope and then plateaued during week 3 . The right leg plateau lasted throughout training , whereas the left leg showed another positive inflection during weeks 7 and 8 . PWR group TW curves showed positive slopes throughout training . STR group PT curves for both legs showed initial positive slopes peaking between weeks 3 and 4 and declining thereafter . The TW curves for both legs showed slight negative slopes across the first 2 wk , steep positive slopes during weeks 3 - 6 , and a final plateau . Because improvements plateau early during PWR and STR training , isokinetic training prescriptions for optimizing strength and power improvements in older persons should use cycles of 3 - 4 wk to maximize gains", "OBJECTIVE To test the efficacy of high-velocity training in healthy older persons . DESIGN A 12-week r and omized trial , with subjects blocked for gender and residence , comparing high-velocity resistance training with a self-paced walking program . SETTING Retirement community . PARTICIPANTS Forty-three volunteers over the age of 70 years . INTERVENTION Power group : high-velocity leg exercises 3 times weekly with weekly increases in resistance combined with 45 minutes of moderate , nonresistance exercise weekly . Walking group : moderate intensity exercise 30 minutes daily , 6 days weekly . MAIN OUTCOME MEASURES Variables measured included leg press peak power and leg extensor strength . Functional performance outcomes included : 6-minute walk distance , Short Physical Performance Battery , Physical Performance Test , and Medical Outcomes Study Short-Form Health Survey . RESULTS Peak power improved 22 % ( p = .004 ) in the power group ( 3.7 + /- 1.0 W/kg to 4.5 + /- 1.4 W/kg ) but did not change in the walking group ( 3.99 + /-.76 W/kg to 3.65 + /-.94 W/kg ) . Leg extensor power at resistance of 50 % , 60 % , and 70 % of body weight increased 50 % , 77 % , and 141 % , respectively , in the power group ( p Strength improved 22 % in the power-trained individuals and 12 % in the walkers ( p functional task performance in either group . One subject developed a radiculopathy during training . CONCLUSIONS Resistance training focusing on speed of movement improved leg power and maximal strength substantially , but did not improve functional performance in healthy high-functioning older volunteers", "Background Depression is a disabling , prevalent condition . Physical activity programs may assist depression management in older people , ameliorate co-morbid conditions and reduce the need for antidepressants . The UPLIFT pilot study assessed the feasibility of older depressed people attending a community-based progressive resistance training ( PRT ) program . The study also aim ed to determine whether PRT improves depressive status in older depressed patients . Methods A r and omised controlled trial was conducted . People aged ≥ 65 years with depressive symptoms were recruited via general practice s. Following baseline assessment , subjects were r and omly allocated to attend a local PRT program three times per week for 10 weeks or a brief advice control group . Follow-up assessment of depressive status , physical and psychological health , functional and quality of life status occurred post intervention and at six months . Results Three hundred and forty six people responded to the study invitation , of whom 22 % had depressive symptoms ( Geriatric Depression Scale , GDS-30 score ≥ 11 ) . Thirty two people entered the trial . There were no significant group differences on the GDS at follow-up . At six months there was a trend for the PRT intervention group to have lower GDS scores than the comparison group , but this finding did not reach significance ( p = 0.08 ) . More of the PRT group ( 57 % ) had a reduction in depressive symptoms post program , compared to 44 % of the control group . It was not possible to discern which specific components of the program influenced its impact , but in post hoc analyses , improvement in depressive status appeared to be associated with the number of exercise sessions completed ( r = -0.8 , p older people with depression can be successfully recruited to a community based PRT program . The program can be offered by existing community-based facilities , enabling its ongoing implementation for the potential benefit of other older people", "BACKGROUND Although exercise has been shown to relieve depression , little is known about its mechanism or dose-response characteristics . We hypothesized that high intensity progressive resistance training ( PRT ) would be more effective than either low intensity PRT or st and ard care by a general practitioner ( GP ) in depressed elderly persons , and that high intensity PRT would provide superior benefits in quality of life , sleep quality , and self-efficacy . METHODS Sixty community-dwelling adults > 60 years with major or minor depression were r and omized to supervised high intensity PRT ( 80 % maximum load ) or low intensity PRT ( 20 % maximum load ) 3 days per week for 8 weeks , or GP care . RESULTS A 50 % reduction in the Hamilton Rating Scale of Depression score was achieved in 61 % of the high intensity , 29 % of the low intensity , and 21 % of the GP care group ( p = .03 ) . Strength gain was directly associated with reduction in depressive symptoms ( r = 0.40 , p = .004 ) , as was baseline social support network type ( F = 3.52 , p = .015 ) , whereas personality type , self-efficacy , and locus of control were unrelated to the antidepressant effect . Vitality quality -of-life scale improved more in the high intensity group than in the others ( p = .04 ) . Sleep quality improved significantly in all participants ( p PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients", "OBJECTIVE To determine the effect of frequency of resistive training on gain in muscle strength and neuromuscular performance in healthy older adults . DESIGN A r and omized controlled trial with subjects assigned either to high-intensity resistance training 1 ( EX1 ) , 2 ( EX2 ) , or 3 ( EX3 ) days per week for 24 weeks or to a control group ( CO ) . SETTING An exercise facility at an academic medical center . SUBJECTS Forty-six community-dwelling healthy men ( n = 29 ) and women ( n = 17 ) aged 65 to 79 years . INTERVENTION Progressive resistance training consisting of three sets of eight exercises targeting major muscle groups of the upper and lower body , at 80 % of one-repetition maximum ( 1-RM ) for eight repetitions , either 1 , 2 , or 3 days per week . MEASURES Dynamic muscle strength ( 1-RM ) using isotonic equipment every 4 weeks , bone mineral density and body composition by dual energy X-ray absorptiometry ( DXA ) , and neuromuscular performance by timed chair rise and 6-meter backward t and em walk . RESULTS For each of the eight exercises , muscle strength increased in the exercise groups relative to CO ( P change averaged 3.9 + /- 2.4 ( CO ) , 37.0 + /- 15.2 ( EX1 ) , 41.9 + /- 18.2 ( EX2 ) , and 39.7 + /- 9.8 ( EX3 ) . The time to rise successfully from the chair 5 times decreased significantly ( P 6-meter backward t and em walk approached significance ( P = .10 ) in the three exercise groups compared with CO . Changes in chair rise ability were correlated to percent changes in quadriceps strength ( r = -0.40 , P lean mass ( r = -0.40 , P resistance exercise achieves muscle strength gains similar to 3 days per week training in older adults and is associated with improved neuromuscular performance . Such improvement could potentially reduce the risk of falls and fracture in older adults", "BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program", "BACKGROUND We aim ed to determine the role of skeletal muscle mitochondrial ATP production rate ( MAPR ) in relation to exercise tolerance after resistance training ( RT ) in chronic heart failure ( CHF ) . METHODS AND RESULTS Thirteen CHF patients ( New York Heart Association functional class 2.3 + /- 0.5 ; Left ventricular ejection fraction 26 + /- 8 % ; age 70 + /- 8 years ) underwent testing for peak total body oxygen consumption ( VO(2peak ) ) , and resting vastus lateralis muscle biopsy . Patients were then r and omly allocated to 11 weeks of RT ( n = 7 ) , or continuance of usual care ( C ; n = 6 ) , after which testing was repeated . Muscle sample s were analyzed for MAPR , metabolic enzyme activity , and capillary density . VO(2peak ) and MAPR in the presence of the pyruvate and malate ( P+M ) substrate combination , representing carbohydrate metabolism , increased in RT ( P MAPR and the change in peak total body oxygen consumption ( VO(2peak ) ) over the study ( r = 0.875 ; P CHF patients and can be favorably altered by muscle strengthening exercise", "OBJECTIVE We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age . DESIGN A r and omized controlled trial with 6-month follow-up was conducted . SETTING The study was performed in the rural town of Kahoku , Japan , the population of which is considered representative of the older population of Japan . PARTICIPANTS We studied 42 healthy volunteers ( 18 men and 24 women ; mean age , 79 years ( range 75 to 87 years ) ) who were r and omly assigned to one of two groups , exercise or control . INTERVENTION Subjects assigned to the exercise group were instructed to exercise for 60 minutes twice a week for 6 months . Subjects in the control group were not instructed to engage in an specific exercise regimen . MEASUREMENTS The following measurements were recorded for both groups at baseline and at 6-month follow-up : ( 1 ) Neurobehavioral function as determined by the following tests : Mini-Mental State Exam ( MMSE ) , Hasegawa Dementia Scale Revised ( HDSR ) , Visuospatial Cognitive Performance Test ( VCP-test ) , Button score , Up & Go test , and Functional Reach ; and ( 2 ) Body mass index and blood pressure . RESULTS The effects of exercise were shown in the Up & Go test , and Functional Reach ( ANOVA with repeated measures ) . CONCLUSION This study demonstrates the acceptability and effectiveness of exercise on neurobehavioral function , even in older people more than 75 years of age", "Background Regular physical activity may improve different aspects of wellbeing in older people , such as quality of life , vitality and depression . However , there is little experimental evidence to support this assumption . Therefore , we examined the effect of different training protocol s on quality of life , vitality and depression of older adults living in long-term care facilities . Methods Subjects ( n = 173 , aged 64 to 94 years , living in long-term care facilities ) , were r and omized to six months of three different moderate-intensity group exercise training protocol s , or to an ' educational ' control condition . Exercise consisted of two 45–60-minute training sessions per week of 1 ) resistance training ; 2 ) all-round , functional training ; or 3 ) a combination of both . Perceived health , the Geriatric Depression Scale ( GDS ) , the Vitality Plus Scale ( VPS ) and the Dementia Quality of Life question naire ( DQoL ) were administered at baseline and after six months . Results In the combined training group a small but significant decline was seen in perceived health , DQoL and VPS score compared to the control group . Conclusions We conclude that neither strength training nor all-round , functional training of moderate intensity is effective in improving quality of life , vitality or depression of older people living in long-term care facilities", "Twenty healthy women aged between 65 and 74 years , trained three times a week , for 16 weeks , on a cycle ergometer , to determine the effects of dynamic resistance training on heart rate variability ( HRV ) . Subjects were allocated to two training groups , high ( HI , n=10 ) and low ( LO , n=10 ) intensity . The HI group performed eight sets of 8 revolutions at 80 % of the maximum resistance to complete 2 pedal revolutions ( 2RM ) ; the LO group performed eight sets of 16 pedal revolutions at 40 % of 2RM . Subjects were tested twice before , as control period ( −4 weeks and 0 weeks ) and once after training ( 16 weeks ) for HRV , maximum voluntary contraction ( MVC ) of knee extensors and peak power ( Pp ) of lower limbs by jumping on a force platform . HRV was measured using time and frequency domain parameters . Two-way ANOVA for repeated measures was performed on all variables ( P HRV was not modified , while MVC and Pp significantly increased . The two proposed forms of dynamic resistance training were appropriate to improve muscle power and strength in elderly females without affecting HRV . More research should verify the effects of an isometric and more prolonged training stimulus on HRV in older subjects", "PURPOSE We evaluated the value of resistance training on measures of physical performance in disabled older women with coronary heart disease ( CHD ) . METHODS The study intervention consisted of a 6-month program of resistance training in a r and omized controlled trial format . Training intensity was at 80 % of the single-repetition maximal lift . Control patients performed light yoga and breathing exercises . Study participants included 42 women with CHD , all > or= 65 yr of age and community dwelling . Subjects were screened by question naire to have low self-reported physical function . The primary study measurements related to the performance of 16 household activities of the Continuous Scale Physical Functional Performance test ( CSPFP ) . These ranged from dressing , to kitchen and cleaning activities , to carrying groceries and walking onto a bus with luggage , and a 6-min walk . Activities were measured in time to complete a task , weight carried during a task , or distance walked . Other measures included body composition , measures of aerobic fitness and strength , and question naire-based measures of physical function and depression score . RESULTS Study groups were similar at baseline by age , aerobic capacity , strength , body composition , and in performing the CSPFP . After conditioning , 13 of 16 measured activities were performed more rapidly , or with increased weight carried , compared with the control group ( all P Maximal power for activities that involved weight-bearing over a distance , increased by 40 % ( P Disabled older women with CHD who participate in an intense resistance-training program improve physical capacity over a wide range of household physical activities . Benefits extend beyond strength-related activities , as endurance , balance , coordination , and flexibility all improved . Strength training should be considered an important component in the rehabilitation of older women with CHD", "OBJECTIVE To determine the effects of 12 weeks of progressive resistance strength training on the isometric strength , explosive power , and selected functional abilities of healthy women aged 75 and over . DESIGN Subjects were matched for age and habitual physical activity and then r and omly assigned into either a control or an exercise group . SETTING The Muscle Function Laboratory , Royal Free Hospital School of Medicine , London . PARTICIPANTS Fifty-two healthy women were recruited through local and national newspapers . Five dropped out before and seven ( 4 exercisers and 3 controls ) during the study . Pre- and posttraining measurements were obtained from 20 exercisers ( median age 79.5 , range 76 to 93 years ) and 20 controls ( median age 79.5 , range 75 to 90 years ) . INTERVENTIONS Training comprised one supervised session ( 1 hour ) at the Medical School and two unsupervised home sessions ( supported by an exercise tape and booklet ) per week for 12 weeks . The training stimulus was three sets of four to eight repetitions of each exercise , using rice bags ( 1 - 1.5 kg ) or elastic tubing for resistance . The exercises were intended specifically to strengthen the muscles considered relevant for the functional tasks , but were not to mimic the functional measurements . No intervention was prescribed for the controls . MEASUREMENTS Pre- and posttraining measurements were made for isometric knee extensor strength ( IKES ) , isometric elbow flexor strength ( IEFS ) , h and grip strength ( HGS ) , leg extensor power ( LEP ) , and anthropometric indices ( Body impedance analysis , arm muscle circumference , and body weight ) . Functional ability tests were chair rise , kneel rise , rise from lying on the floor , 118-m self-paced corridor walk , stair climbing , functional reach , stepping up , stepping down , and lifting weights onto a shelf . Pre- and posttraining comparisons were made using analysis of variance or analysis of covariance ( using weight as a covariate ) for normally distributed continuous data and one-sided Fishers exact test ( 2 x 2 table ) for discontinuous data . RESULTS Improvements in IKES ( mean change 27 % , P = .03 ) , IEFS ( 22 % , P = .05 ) , HGS ( 4 % , P = .05 ) , LEP/kg ( 18 % , P = .05 ) were associated with training , but the improvement in LEP ( 18 % , P = .11 ) did not reach statistical significance . There was an association between training and a reduction in normal pace kneel rise time ( median change 21 % , P = .02 ) and a small improvement in step up height ( median 5 % , P = .005 ) . The other functional tests did not improve . CONCLUSIONS Progressive resistance exercise can produce substantial increases in muscle strength and in power st and ardized for body weight in healthy , very old women . However , isolated increases in strength and LEP/kg may confer only limited functional benefit in healthy , independent , very old women", "Resistance training can improve strength and functional performance , but there is little information about the effect of training intensity on functional performance in older adults . The purpose of this study was to determine the effect of 12 weeks of heavy ( 80 % of 1 repetition maximum [ 1RM ] ) and moderate ( 60 % of 1RM ) resistance training on functional performance in healthy , inactive older adults , ages 60–74 years . Volunteer subjects were assigned r and omly to a control group ( CS , n = 10 ) , heavy resistance training group ( HRT , n = 11 ) , or moderate resistance training group ( MRT , n = 12 ) and participated in 12 weeks of strength training , 3 times per week . Performance measurements included 1RM lower-body strength , chair-rising time , walking velocity , stair-climbing time , and flexibility . Significant differences between HRT and MRT were found for 1RM strength of the lower limbs after the training period . Functional performance improved similarly for both HRT and MRT after the training period . Functional performance can be improved significantly with either heavy or moderate resistance training , without significant differences in the effectiveness of the 2 training protocol", "OBJECTIVES To determine the independent and combined effects of progressive resistance muscle strength training ( PRMST ) and megestrol acetate ( MA ) on strength , muscle mass , and function in older recuperative care patients . DESIGN Double-blind , r and omized , controlled intervention using a two-by-two factorial design and conducted between 1999 and 2001 . SETTING University-affiliated Department of Veterans Affairs hospital . PARTICIPANTS Twenty-nine patients ( mean age 79.4 + /- 7.4 , 90 % white ) aged 65 and older and had recent functional decline . INTERVENTIONS After r and omization to one of four treatment groups ( low-resistance exercises plus 800 mg per day of MA or a placebo or high-intensity PRMST plus 800 mg/d of MA or placebo ) , subjects received training and the drug or placebo for 12 weeks . MEASUREMENTS Change in muscle strength , mid-thigh muscle area , and aggregate functional performance score as assessed using analysis of covariance . RESULTS Five subjects withdrew from the study before its completion . Based on intent-to-treat analyses , subjects who received high-intensity PRMST and placebo experienced the greatest strength gains . The addition of MA was associated with worse outcomes than with high-intensity exercise training alone , especially with regard to the leg exercises . Post hoc analysis demonstrated that subjects who received high-intensity PRMST and placebo experienced significantly greater percentage increases in leg strength than subjects in either of the MA treatment groups ( P MA on physical function . In general , subjects who received MA experienced a deterioration in aggregate physical function scores , whereas the remaining subjects improved ( -0.80+/-0.40 vs 0.48+/-0.41 , P=.04 ) . There was not a significant interaction between exercise and MA for any outcome . CONCLUSION High-intensity PRMST is a safe and well-tolerated exercise regimen for frail elderly patients . The addition of MA appears to blunt the beneficial effects of PRMST , result ing in less muscle strength and functional performance gains", "BACKGROUND Muscle power ( force x velocity ) recedes at a faster rate than strength with age and may also be a stronger predictor of fall risk and functional decline . The optimal training paradigm for improving muscle power in older adults is not known , although some literature suggests high velocity , low load training is optimal in young adults . METHODS One hundred twelve healthy older adults ( 69 + /- 6 years ) were r and omly assigned to either explosive resistance training at 20 % ( G20 ) , 50 % ( G50 ) , or 80 % ( G80 ) one repetition maximum ( 1RM ) for 8 - 12 weeks or to a nontraining control group ( CON ) . Participants trained twice per week ( five exercises ; three sets of eight rapidly concentric and slow eccentric repetitions ) using pneumatic resistance machines . Repeated- measures analysis of variance and covariance ( ANOVA and ANCOVA ) were used to determine the effects of training . RESULTS Average peak power increased significantly and similarly in G80 ( 14 + /- 8 % ) , G50 ( 15 + /- 9 % ) , and G20 ( 14 + /- 6 % ) compared to CON ( 3 + /- 6 % ) ( p average strength ( r = .40 , p = .0009 ) and endurance ( r = .43 , p = .0005 ) . Average strength increased in G80 ( 20 + /- 7 % ) , G50 ( 16 + /- 7 % ) , and G20 ( 13 + /- 7 % ) compared to CON ( 4 + /- 4 % ) ( p Average muscle endurance increased in G80 ( 185 + /- 126 % , p Peak muscle power may be improved similarly using light , moderate , or heavy resistances , whereas there is a dose-response relationship between training intensity and muscle strength and endurance changes . Therefore , using heavy loads during explosive resistance training may be the most effective strategy to achieve simultaneous improvements in muscle strength , power , and endurance in older adults", "Background Lower limb strengthening exercises are an important component of the treatment for knee osteoarthritis ( OA ) . Strengthening the hip abductor and adductor muscles may influence joint loading and /or OA-related symptoms , but no study has evaluated these hypotheses directly . The aim of this r and omised , single-blind controlled trial is to determine whether hip abductor and adductor muscle strengthening can reduce knee load and improve pain and physical function in people with medial compartment knee OA . Methods / Design 88 participants with painful , radiographically confirmed medial compartment knee OA and varus alignment will be recruited from the community and r and omly allocated to a hip strengthening or control group using concealed allocation stratified by disease severity . The hip strengthening group will perform 6 exercises to strengthen the hip abductor and adductor muscles at home 5 times per week for 12 weeks . They will consult with a physiotherapist on 7 occasions to be taught the exercises and progress exercise resistance . The control group will be requested to continue with their usual care . Blinded follow up assessment will be conducted at 12 weeks after r and omisation . The primary outcome measure is the change in the peak external knee adduction moment measured during walking . Question naires will assess changes in pain and physical function as well as overall perceived rating of change . An intention-to-treat analysis will be performed using linear regression modelling and adjusting for baseline outcome values and other demographic characteristics . Discussion Results from this trial will contribute to the evidence regarding the effect of hip strengthening on knee loads and symptoms in people with medial compartment knee OA . If shown to reduce the knee adduction moment , hip strengthening has the potential to slow disease progression . Trial Registration Australia New Zeal and Clinical Trials Registry", "Body composition changes and loss of functionality in the elderly are related to subst and ard diets and progressive sedentariness . The aim of this study was to assess the impact of an 18-mo nutritional supplementation and resistance training program on health functioning of elders . Healthy elders aged > or = 70 y were studied . Half of the subjects received a nutritional supplement . Half of the supplemented and nonsupplemented subjects were r and omly assigned to a resistance exercise training program . Every 6 mo , a full assessment was performed . A total of 149 subjects were considered eligible for the study and 98 ( 31 supplemented and trained , 26 supplemented , 16 trained and 25 without supplementation or training ) completed 18 mo of follow-up . Compliance with the supplement was 48 % , and trained subjects attended 56 % of programmed sessions . Activities of daily living remained constant in the supplemented subjects and decreased in the other groups . Body weight and fat-free mass did not change . Fat mass increased from 22.2 + /- 7.6 to 24.1 + /- 7.7 kg in all groups . Bone mineral density decreased less in both supplemented groups than in the nonsupplemented groups ( ANOVA , P Serum cholesterol remained constant in both supplemented groups and in the trained groups , but it increased in the control group ( ANOVA , P Upper and lower limb strength , walking capacity and maximal inspiratory pressure increased in trained subjects . In conclusion , patients who were receiving nutritional supplementation and resistance training maintained functionality , bone mineral density and serum cholesterol levels and improved their muscle strength", "BACKGROUND Aging is associated with reductions in muscle mass and strength , but nutrition and exercise interventions can delay this progression and enhance the quality of life . OBJECTIVE We examined whether the predominant source of protein consumed by older men influenced measures of muscle size and strength , body composition , resting energy expenditure , and skeletal muscle creatine concentrations in response to 12 wk of resistive training . DESIGN After consuming a lactoovovegetarian ( LOV ) diet for 2 wk , 21 men aged 65 + /- 5 y were r and omly assigned to either consume a beef-containing ( BC ) diet ( n = 10 ) or to continue the LOV diet ( n = 11 ) throughout resistive training . The BC diet included 0.6 g protein . kg(-1 ) . d(-1 ) from beef and the LOV diet included 0.6 g protein . kg(-1 ) . d(-1 ) from textured vegetable protein ( soy ) sources . The remaining protein in the diets came from self-selected LOV sources . RESULTS The mean total protein intake for both groups ranged from 1.03 to 1.17 g. kg(-1 ) . d(-1 ) during the intervention . Men in both groups had improvements ( 14 - 38 % ) in maximal dynamic strength of all the muscle groups trained with no significant difference between groups . With resistive training , cross-sectional muscle area of the vastus lateralis increased in both groups ( 4.2 + /- 3.0 % and 6.0 + /- 2.6 % for the LOV and BC groups , respectively ) with no significant difference between groups . Body composition , resting energy expenditure , and concentrations of muscle creatine , phosphocreatine , and total creatine did not differ significantly between groups or change over time . CONCLUSIONS These data suggest that increases in muscle strength and size were not influenced by the predominant source of protein consumed by older men with adequate total protein intake", "BACKGROUND there have been few population -based , r and omized controlled trials on the effects of strength or endurance training on cardiovascular fitness in older women . OBJECTIVE to study the effects of strength or endurance training on cardiovascular fitness in women aged 76 - 78 years . DESIGN a population -based , r and omized controlled trial . SETTING exercise laboratory in a university faculty of sport and health sciences . SUBJECTS we r and omly assigned 42 medically-screened women aged 76 - 78 years , drawn from the population register to strength ( n=16 ) , endurance ( n=15 ) or control ( n=11 ) groups . METHODS subjects in the two exercise groups performed a supervised , individually tailored 18-week strength or endurance training programme . Controls continued with physical activity at their normal level . RESULTS the strength training group showed an increase in cycle ergometer peak power from 68.1 to 70.3 W ( P=0.035 compared with controls ) . Their peak power per kg body weight increased from 1.02 to 1.05 , while that of the endurance training group increased from 0.91 to 0.93 ( P=0.027 and P=0.049 respectively ) . Peak oxygen uptake increased from 18.1 to 19.7 ml x kg(-1 ) x min(-1 ) in the strength and from 17.1 to 18.2 in the endurance group ( non-significant ) . Six subjects ( 19 % ) in the exercise groups withdrew from the study because of health problems . CONCLUSIONS even with its limitations , the study suggests that the effect of 18-week strength or endurance training on cardiovascular fitness among women aged > /=75 is relatively small . Furthermore , health problems can emerge during training programmes in medically-screened elderly women", "Physical exercise is expected to improve and maintain physical function in older people , thus promoting health and preventing or postponing the onset of disability in later life . The Sendai Silver Center Trial ( SSCT ) was a r and omized controlled trial design ed to evaluate the efficacy of exercise training among healthy free-living older people . Sixty-five eligible participants , aged from 60 to 81 years , were r and omly allocated to an exercise group or a control group . The subjects in the exercise group were asked to attend training classes at the Sendai Silver Center , a municipal health and welfare facility in the center of Sendai City , at least twice a week for 25 weeks . Each training class , lasting two hours , started with a warm-up session , followed by an endurance session with a bicycle ergometer , and a resistance exercise training session using rubber films , and ended with a cool-down session . The subjects in the control group were asked to attend recreational classes at the Center twice a month . There were no drop-outs or accidents during the intervention . Comparison of maximum oxygen consumption ( VO2max ) before and after the 25-week intervention revealed a significant increase in the exercise group ( 2.1 ml/kg/min ) but no significant change in the control group . Our result is equivalent to the participants becoming younger in aerobic capacity by five years after six months of exercise training", "BACKGROUND AND PURPOSE Knowledge concerning the applicability and the effect of high-intensity exercise programs is very limited for older people with severe cognitive and physical impairments . The primary aim of this study was to evaluate the applicability of a high-intensity functional weight-bearing exercise program among older people who are dependent in activities of daily living and living in residential care facilities . A second aim was to analyze whether cognitive function was associated with the applicability of the program . SUBJECTS The subjects were 91 older people ( mean age=85.3 years , SD=6.1 , range=68 - 100 ) who were dependent in personal activities of daily living and r and omly assigned to participate in an exercise intervention . Their mean score for the Mini-Mental State Examination ( MMSE ) was 17.5 ( SD=5.0 , range=10 - 29 ) . METHODS A high-intensity functional weight-bearing exercise program was performed in groups of 3 to 7 participants who were supervised by physical therapists . There were 29 exercise sessions over 13 weeks . Attendance , intensity of lower-limb strength and balance exercises , and occurrence and seriousness of adverse events were the outcome variables in evaluating the applicability of the program . RESULTS The median attendance rate was 76 % . Lower-limb strength exercises with high intensity were performed in a median of 53 % of the attended exercise sessions , and balance exercises with high intensity were performed in a median of 73 % of the attended exercise sessions . The median rate of sessions with adverse events was 5 % . All except 2 adverse events were assessed as minor and temporary , and none led to manifest injury or disease . No significant differences were observed in applicability when comparing participants with dementia and participants without dementia . In addition , there was no significant correlation between applicability and the MMSE score . DISCUSSION AND CONCLUSION The results suggest that a high-intensity functional weight-bearing exercise program is applicable for use , regardless of cognitive function , among older people who are dependent in activities of daily living , living in residential care facilities , and have an MMSE score of 10 or higher", "BACKGROUND Resistance training increases the skeletal muscle strength and functional ability of chronic heart failure patients . However , there is limited data regarding the effect of resistance training on the hemodynamic responses and peak oxygen consumption ( peak VO(2 ) ) of chronic heart failure patients treated with beta-blocker . This study examined the effect of resistance training on hemodynamics , peak aerobic capacity , muscle strength and quality of life of chronic heart failure patients on beta-blockers medication . METHODS Fifteen men diagnosed with chronic heart failure were matched to either a resistance training program or non-training control group . At baseline and after 8 weeks of resistance training patients performed both Balke incremental and maximal strength tests and completed quality of life question naires . RESULTS The resistance training group demonstrated a significant increase of walking time and peak VO(2 ) by 11.7 % ( p=0.002 ) and approximately 19 % ( p Peak VO(2 ) was significantly correlated with both walking time ( r=0.54 , p=0.038 ) and change in total weight lifted ( r=0.55 , p=0.034 ) . Quality of life significantly increased by 87 % ( p=0.030 ) . The improvement in quality of life was correlated with post training peak VO(2 ) ( r=0.58 , p=0.025 ) and total weight lifted during the post maximal strength test ( r=-0.52 , p=0.047 ) . CONCLUSIONS The benefits from resistance training for chronic heart failure patients on beta-blocker medication included an increased aerobic and exercise capacity , skeletal muscle strength and most importantly , an improvement in the quality of life , which is the main goal of cardiac rehabilitation programs . Furthermore , with appropriate supervision , it is recommended that resistance exercise be added to the exercise rehabilitation program of these patients when possible", "The purpose of this study was to determine whether strength training could reduce the deficit in plantarflexion ( PF ) maximal voluntary contraction ( MVC ) torque observed in previous studies in older subjects relative to young adults . Accordingly , the effects of a 6-month strength training program on the muscle and neural properties of the major muscle groups around the ankle were examined . PF and dorsiflexion ( DF ) isometric MVC torques were measured and surface electromyographic activity of the triceps surae and tibialis anterior muscles was recorded . The strength training program was very effective in improving strength in PF ( + 24.5 % ) , and it thus reduced the DF-to-PF MVC torque ratio ; in addition , it also induced gains in DF ( + 7.6 % ) . Thus , there must be an improvement in ankle joint stability . In PF , gains were due particularly to a modification of the agonist neural drive ; in DF , the gains appeared to be the consequence of a reduction in antagonist coactivation . Our findings indicate that the investigation of one muscle group should always be accompanied by examination of its antagonist muscle group", "OBJECTIVES To determine the effects of a 12-week , home-based resistance exercise program on strength , body composition , and activities of daily living ( ADLs ) in men and women with Charcot-Marie-Tooth ( CMT ) disease and to design an ADL-based resistance exercise prescription template . DESIGN Double-blind , placebo-controlled study . SETTING Testing in a university setting ; exercise in patients ' homes . PARTICIPANTS Twenty CMT patients who volunteered . INTERVENTION Subjects progressively strength trained at home 3 d/wk for 12 weeks . MAIN OUTCOME MEASURES Timed ADLs , isometric strength , and body composition . RESULTS Absolute strength was greater in men with CMT in only 4 of 10 baseline measures ( P compliance was 87 % with no gender differences . At baseline , women had 80 % of normal strength in 4 of 10 measures , whereas men did not achieve 80 % of normal strength in any measure . After training , women had 80 % of normal strength in 8 of 10 measures , whereas men only had 80 % of normal strength in 1 . Training volumes and strength change scores showed no gender differences . ADLs improved after training with no gender differences ( P chair-rise time to estimate starting weights for lower body and supine rise for upper body . CONCLUSIONS Resistance training improved strength and ADLs equally in men and women . We design ed an exercise prescription recommendation , based on ADL performance", "BACKGROUND To study the effects of resistance training on muscle strength and size in older people , we enrolled 8 men and 17 women ( mean age 68.2 + /- 1 SEM ) into a one-year exercise trial . METHODS Subjects were r and omly assigned to exercise or control groups . Muscle biopsies were obtained from 11 subjects ( 8 exercisers/3 controls ) at baseline and after 15 weeks ; exercisers underwent another biopsy at 30 weeks . After testing maximum strength using the 1-RM method , the exercisers began a 12-exercise circuit ( 3 sets of 8 repetitions at 75 % of 1-RM ) , 3 times a week . The controls repeated the strength testing every 15 weeks . They were asked to continue usual activities and not to start any exercise program . RESULTS With exercise , muscle strength increased , average increases ranging from 30 % ( hip extensors ) to 97 % ( hip flexors ) . Strength increased rapidly over 3 months , then plateaued for the duration of the experiment . No strength changes were observed in sedentary controls . Cross-sectional area of type 1 muscle fibers increased in exercisers by 15 weeks ( 29.4 + /- 1 % , p Type 2 fiber area did not change at 15 weeks , but increased by 30 weeks of training ( 66.6 + /- 9.5 % , p moderate to high intensity resistance training may be carried out by healthy older adults with reasonable compliance , and that such training leads to sustained increases in muscle strength . These improvements are rapidly achieved and are accompanied by hypertrophy of both type 1 and type 2 muscle fibers", "OBJECTIVES To better underst and how immobilization and surgery affect muscle size and function in the elderly and to identify effective training regimes . DESIGN A prospect i ve r and omized , controlled study . SETTING Bispebjerg University Hospital , Copenhagen , Denmark . PARTICIPANTS Thirty-six patients ( aged 60 - 86 ) scheduled for unilateral hip replacement due to primary hip osteoarthrosis . INTERVENTION Patients were r and omized to st and ard home-based rehabilitation ( 1 h/d x 12 weeks ) , unilateral neuromuscular electrical stimulation of the operated side ( 1 h/d x 12 weeks ) , or unilateral resistance training of the operated side ( 3/wk x 12 weeks ) . MEASUREMENTS Hospital length of stay ( LOS ) , quadriceps muscle cross-sectional area ( CSA ) , isokinetic muscle strength , and functional performance . Patients were tested presurgery and 5 and 12 weeks postsurgery . RESULTS Mean+/-st and ard error LOS was shorter for the resistance training group ( 10.0+/-2.4 days , P st and ard rehabilitation group ( 16.0+/-7.2 days ) . Resistance training , but not electrical stimulation or st and ard rehabilitation , result ed in increased CSA ( 12 % , P muscle strength ( 22 - 28 % , P Functional muscle performance increased after resistance training ( 30 % , P electrical stimulation ( 15 % , P st and ard rehabilitation . CONCLUSION Postoperative resistance training effectively increased maximal muscle strength , muscle mass , and muscle function more than a st and ard rehabilitation regime . Furthermore , it markedly reduced LOS in elderly postoperative patients", "BACKGROUND PATIENTS : with chronic airflow obstruction are often limited by muscle fatigue and weakness . As exercise rehabilitation programmes have produced modest improvements at best a study was design ed to determine whether specific muscle training techniques are helpful . METHODS : Thirty four patients with chronic airflow limitation ( forced expiratory volume in one second ( FEV1 ) 38 % of predicted values ) were stratified for FEV1 to vital capacity ( VC ) ratio less than 40 % and arterial oxygen desaturation during exercise and r and omised to a control or weightlifting training group . In the experimental group training was prescribed for upper and lower limb muscles as a percentage of the maximum weight that could be lifted once only . It was carried out three times a week for eight weeks . RESULTS : Three subjects dropped out of each group ; results in the remaining 14 patients in each group were analysed . Adherence in the training group was 90 % . In the trained subjects muscle strength and endurance time during cycling at 80 % of maximum power output increased by 73 % from 518 ( SE69 ) to 898 ( 95 ) s , with control subjects showing no change ( 506 ( 86 ) s before training and 479 ( 89 ) s after training ) . No significant changes in maximum cycle ergometer exercise capacity or distance walked in six minutes were found in either group . Responses to a chronic respiratory question naire showed significant improvements in dyspnoea and mastery of daily living activities in the trained group . CONCLUSIONS : Weightlifting training may be successfully used in patients with chronic airflow limitation , with benefits in muscle strength , exercise endurance , and subjective responses to some of the dem and s of daily living", "The purpose of this study was to determine whether a high intensity ( HI ) versus a moderate ( MI ) or low-intensity ( LI ) training program would be more effective in improving the isokinetic knee extension muscular performance in healthy inactive men and women . Sixty-four participants , men and women , were r and omly assigned to one of four groups : control group ( C ) , LI ( 50 % of 1RM ) , the MI group ( 70 % of 1RM ) and the HI ( 90 % of 1RM ) . Participants exercised on three resistance exercise machines : leg extension , leg curls and leg press . The isokinetic testing method ( concentric mode ) applied prior to and at the end of the training period ( 16 weeks , three 3 times per week ) to assess the knee muscular performance . MANOVA repeated measures revealed that the HI group demonstrated the most strength gains following a speed specificity pattern ( most considerable improvement occurred at or near slow speeds from 7.3 % to 11.2 % for male and from 2.3 % to 15.2 % for female ) . In addition , males demonstrated a greater improvement of knee extension power output than females . In conclusion , HI strength training is proposed for elderly men and women as the most effective protocol . Furthermore only at low-velocity testing , women of the HI showed a greater change than men ( p strength increase in relation to various testing velocities , a greater increase was found in HI at low velocities , with the other training groups exhibiting almost similar strength increase at all tested speeds", "Summary This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility", "CONTEXT Adiponectin and leptin are closely related to weight control and energy balance , whereas exercise affects elderly metabolic regulation and functional capacity . OBJECTIVE The objective of this study was to investigate leptin and adiponectin responses in elderly males after exercise training and detraining . DESIGN The study design was a 1-yr r and omized controlled trial . SETTING The study was performed at the Laboratory of Physical Education and Sport Science Department . PARTICIPANTS Fifty inactive men [ age , 65 - 78 yr ; body mass index ( BMI ) , 28.7 - 30.2 kg/m2 ] were recruited from a volunteer data base by word of mouth and fliers sent to medical practitioners , physiotherapists , and nursing homes in the local community . INTERVENTION(S ) Participants were r and omly assigned to a control ( n = 10 ) , low-intensity ( n = 14 ) , moderate-intensity ( n = 12 ) , or high-intensity training ( HI ; n = 14 ) group . Resistance training ( 6 months , 3 d/wk , 10 exercises/three sets ) was followed by 6 months of detraining . MAIN OUTCOME MEASURE(S ) Strength , exercise energy cost , skinfold sum , body weight , maximal oxygen consumption , resting metabolic rate ( RMR ) , and plasma leptin and adiponectin were determined at baseline and after training and detraining . RESULTS Strength , maximal oxygen consumption , RMR , and exercise energy cost increased ( P Skinfold sum and BMI were reduced by resistance training ( P Leptin was diminished ( P adiponectin increased ( P percent leptin decrease was associated ( P percent BMI decrease and the percent RMR increase , whereas the percent adiponectin increase was associated ( P BMI decrease . CONCLUSIONS Resistance training and detraining may alter leptin and adiponectin responses in an intensity-dependent manner . Leptin and adiponectin changes were strongly associated with RMR and anthropometric changes", "This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training . Forty male and female subjects ( 69.2 + /- 0.6 yr ) were assigned to a control group or 6 mo of endurance ( ET ) or resistance training ( RT ) . We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle . The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties , glycolytic ATP synthesis , and contractile ATP dem and . Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms , metabolite concentrations , and mitochondrial volume densities . The ET group showed changes in all energetic pathways : oxidative capacity ( + 31 % ) , contractile ATP dem and ( -21 % ) , and glycolytic ATP supply ( -56 % ) . The RT group had a large increase in oxidative capacity ( 57 % ) . Only the RT group exhibited change in structural properties : a rise in mitochondrial volume density ( 31 % ) and muscle size ( 10 % ) . These results demonstrate large energetic , but smaller structural , adaptations by elderly muscle with exercise training . The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle . Thus elderly muscle remains adaptable to chronic exercise , with large energetic changes accompanying both ET and RT", "OBJECTIVES To examine the effects of 18-month aerobic walking and strength training programs on static postural stability among older adults with knee osteoarthritis . DESIGN R and omized , single-blind , clinical trial of therapeutic exercise . SETTING Both center-based ( university ) and home-based . PARTICIPANTS A cohort of 103 older adults ( age = 60 years ) with knee osteoarthritis who were participants in a large ( n = 439 ) clinical trial and who were r and omly assigned to undergo biomechanical testing . INTERVENTION An 18-month center- ( 3 months ) and home-based ( 15 months ) therapeutic exercise program . The subjects were r and omized to one of three treatment arms : ( 1 ) aerobic walking ; ( 2 ) health education control ; or ( 3 ) weight training . MEASUREMENTS Force platform static balance measures of average length ( Rm ) of the center of pressure ( COP ) , average velocity ( Vel ) of the COP , elliptical area ( Ae ) of the COP , and balance time ( T ) . Measures were made under four conditions : eyes open , double- and single-leg stances and eyes closed , double- and single-leg stances . RESULTS In the eyes closed , double-leg stance condition , both the aerobic and weight training groups demonstrated significantly better sway measures relative to the health education group . The aerobic group also demonstrated better balance in the eyes open , single-leg stance condition . CONCLUSIONS Our results suggest that long-term weight training and aerobic walking programs significantly improve postural sway in older , osteoarthritic adults , thereby decreasing the likelihood of larger postural sway disturbances relative to a control group", "Objective : Comparison of two flooring types – carpet and vinyl – in the bed areas , and two modes of physiotherapy – conventional therapy and additional leg strengthening exercises – in avoiding falls . Design : R and omized 2 × 2 controlled trial . Setting : Elderly care rehabilitation ward in a community hospital . Subjects : Fifty-four consecutive patients referred for rehabilitation . Outcome measures : The incidence of falls , and the change in strength . Results : There were 10 falls on carpet , and only a single fall on vinyl floor covering ( relative risk 8.3 , 95 % confidence interval 0.95–73 , p = 0.05 ) . There were four falls in those receiving additional exercise , and seven falls in those receiving only conventional physiotherapy ( relative risk 0.21 , 95 % confidence interval 0.04–1.2 , p = 0.12 ) . Fifty-nine per cent of patients were able to complete strength measurements on admission and discharge . In these , h and grip strength improved more in those given additional exercise than conventional physiotherapy ( 2.1 kg versus – 0.3 kg , p preventing falls on a rehabilitation ward , but within this low-powered study , there was a strong trend towards vinyl being superior ", "The authors compared heart-rate and blood-pressure responses to typical isometric ( ISO ) and isokinetic ( 90 degrees /s ) eccentric ( ECC ) resistance-training protocol s in older adults . Twenty healthy older adults ( 74 + /- 5 years old ) performed r and omly ordered ISO and isokinetic ECC exercise ( 3 sets of 10 repetitions ) at a target intensity of 100 % of their peak ISO torque value . Heart rate and systolic ( SBP ) and diastolic ( DBP ) blood pressures were recorded continuously , and mean arterial pressure ( MAP ) and rate-pressure product ( RPP ) were calculated . ECC peak torque ( 139 + /- 33 N. m ) was significantly greater than ISO peak torque ( 115 + /- 26 N. m ; p variables increased significantly ( p . Changes in SBP , DBP , MAP , and RPP were significantly greater during ISO exercise than during ECC exercise ( p isokinetic ECC exercise program enables older adults to work at the same torque output with less cardiovascular stress than ISO exercise", "The authors assessed the effects of resistance training and walking exercise on measures of functional fitness . Sixty-four volunteers ( average age 83.5 years ) from an independent-living facility were r and omly assigned to walking , resistance training , or control groups . Participants in the walking and resistance-training groups engaged in two exercise sessions per week for 16 weeks . Measures of functional fitness included upper and lower body strength , hip and shoulder flexibility , agility and balance , coordination , blood pressure , and resting heart rate . Repeated measures analysis of variance was used to examine pretest to posttest differences . Both exercise groups showed significant improvements relative to control group in upper and lower body strength , shoulder flexibility , and agility and balance exercise . Findings demonstrate that exercise can lead to improvements in multiple domains of functional fitness even among very old , previously sedentary individuals , possibly making activities of daily living easier to perform", "OBJECTIVE To evaluate the effects of isokinetic exercise versus a program of patient education on pain and function in older persons with knee osteoarthritis . DESIGN A r and omized , comparative clinical trial , with interventions lasting 8 weeks and evaluations of 12 weeks . SETTING An outpatient Veterans Affairs Medical Center clinic and an affiliated university hospital . PATIENTS One hundred thirteen men and women between 50 and 80 years old with diagnosed osteoarthritis of the knee ; 98 completed the entire assigned treatment . INTERVENTION Patients received either a regimen of isokinetic exercise of the quadriceps muscle three times weekly over 8 weeks or a series of 4 discussion s and lectures led by health care professionals . MAIN OUTCOME MEASURES Variables studied for change were isokinetic and isometric quadriceps strength , pain and function determined by categorical and visual analog scales , and overall status using physician and patient global evaluations by the Arthritis Impact Scale , version 2 , Western Ontario McMaster 's Arthritis Index , and Medical Outcome Study Short Form 36 . RESULTS Both treatment groups showed significant strength gains ( p pain scores for more of the variables measured than those receiving education . Both groups had positive functional outcomes and slightly improved measures of overall status . CONCLUSIONS Isokinetic exercise is an effective and well-tolerated treatment for knee osteoarthritis , but a much less costly education program also showed some benefits", "PURPOSE This study assessed the impact of a low cost , multicomponent physical activity intervention for older adults with lower extremity osteoarthritis . DESIGN AND METHODS A r and omized controlled trial compared the effects of a facility-based multiple-component training program followed by home-based adherence ( n = 80 ) to a wait list control group ( n = 70 ) . Assessment s were conducted at baseline and at 2 and 6 months following r and omization . The training program consisted of range of motion , resistance training , aerobic walking , and education-group problem solving regarding self-efficacy for exercise and exercise adherence . All training group participants developed individualized plans for posttraining adherence . RESULTS Relative to the persons in the control group , individuals who participated in the exercise program experienced a statistically significant improvement in exercise efficacy , a 48.5 % increase in exercise adherence , and a 13.3 % increase in 6-min distance walk that were accompanied by significant decreases in lower extremity stiffness at 2 and 6 months . Program participants also experienced a significant decrease in lower extremity pain and a borderline significant improvement in efficacy to adhere to exercise over time at 6 months ( p = .052 ) . In contrast , persons in the control group deteriorated over time on the efficacy and adherence measures and showed no change on the other measures . No adverse health effects were encountered . IMPLICATION S These benefits indicate that this low-cost intervention may hold great promise as one of a growing number of public health intervention strategies for older adults in the United States with osteoarthritis", "To evaluate the effects of 26 wk of aerobic and resistance training on the incidence of injury and program adherence in 70- to 79-yr-old men and women , 57 healthy volunteers ( 25 males , 32 females ) were r and omly assigned to a walk/jog ( W/J , N = 21 ) , strength ( STREN , N = 23 ) , or control ( CONT , N = 13 ) group . Walk/jog training was for 30 - 45 min , 3 d.wk-1 with intensity equal to 40 - 70 % heart rate max reserve ( HRmax reserve ) during the first 13 wk , and 75 - 85 % HRmax reserve for weeks 14 - 26 . STREN training consisted of one set ( 10 - 12 repetitions ) each of 10 variable resistance exercises performed to volitional fatigue . Forty-nine of the original participants completed the training program . Walk/jog training increased VO2max from 22.5 to 27.1 ml.kg-1.min-1 ( P less than or equal to 0.05 ) while STREN and CONT showed no change . STREN improved significantly in chest press and leg extension strength ( P less than or equal to 0.05 ) while W/J and CONT showed no change . Adherence to training was 20/23 ( 87 % ) and 17/21 ( 81 % ) in STREN and W/J , respectively . One repetition maximum ( 1-RM ) strength testing result ed in 11 injuries in the 57 subjects ( 19.3 % ) while STREN training result ed in only two injuries in 23 subjects ( 8.7 % ) . Walk training during weeks 1 - 13 result ed in one injury in 21 subjects ( 4.8 % ) . Eight of 14 subjects ( 57 % ) who began jogging intervals at week 14 incurred an injury : two of eight ( 25 % ) of the men and all of the women ( 6 of 6 ) . All W/J training injuries were to the lower extremity . ( ABSTRACT TRUNCATED AT 250 WORDS", "The purpose of this study was to investigate the effects of a 12-week resistance-training program on muscle strength and mass in older adults . Thirty-three inactive participants ( 60 - 74 years old ) were assigned to 1 of 3 groups : high-resistance training ( HT ) , moderate-resistance training ( MT ) , and control . After the training period , both HT and MT significantly increased 1-RM body strength , the peak torque of knee extensors and flexors , and the midthigh cross-sectional area of the total muscle . In addition , both HT and MT significantly decreased the abdominal circumference . HT was more effective in increasing 1-RM strength , muscle mass , and peak knee-flexor torque than was MT . These data suggest that muscle strength and mass can be improved in the elderly with both high- and moderate-intensity resistance training , but high-resistance training can lead to greater strength gains and hypertrophy than can moderate-resistance training", "OBJECTIVES To test the hypothesis that physical exercise induces an antiinflammatory response that is associated with reduced chronic activation of the tumor necrosis factor (TNF)-alpha system in frail elders and that the increase in muscle strength after resistance training is limited by systemic low- grade inflammation . DESIGN A 12-week controlled resistance-training study . SETTING Nursing homes in Copenhagen , Denmark . PARTICIPANTS Twenty-one frail nursing home residents aged 86 to 95 completed the study . INTERVENTION Ten participants were r and omized to a program of resistance training of knee extensors and flexors three times a week for 12 weeks ; the remaining 11 participants served as a control group who joined social activities supervised by an occupation therapist . MEASUREMENTS Muscle strength , plasma levels of TNF-alpha , soluble TNF receptor (sTNFR)-1 , and interleukin (IL)-6 were measured before and at the end of the intervention period . RESULTS The training program improved muscle strength but did not affect plasma levels of TNF-alpha and sTNFR-I or IL-6 . However , plasma levels of sTNFR-I at baseline were inversely correlated with the increase in muscle strength . CONCLUSION Low- grade activation of the TNF system could limit the increase in muscle strength after resistance training in the oldest old . Furthermore , data suggest that the antiinflammatory response induced by 12 weeks of resistance training is not sufficient to reduce chronic activation of the TNF system , but the small sample size limited this interpretation", "The ability to develop muscle force rapidly may be a very important factor to prevent a fall and to perform other tasks of daily life . However , information is still lacking on the range of training-induced neuromuscular adaptations in elderly humans recovering from a period of disuse . Therefore , the present study examined the effect of three types of training regimes after unilateral prolonged disuse and subsequent hip-replacement surgery on maximal muscle strength , rapid muscle force [ rate of force development ( RFD ) ] , muscle activation , and muscle size . Thirty-six subjects ( 60 - 86 yr ) were r and omized to a 12-wk rehabilitation program consisting of either 1 ) strength training ( 3 times/wk for 12 wk ) , 2 ) electrical muscle stimulation ( 1 h/day for 12 wk ) , or 3 ) st and ard rehabilitation ( 1 h/day for 12 wk ) . The nonoperated side did not receive any intervention and thereby served as a within-subject control . Thirty subjects completed the trial . In the strength-training group , significant increases were observed in maximal isometric muscle strength ( 24 % , P contractile RFD ( 26 - 45 % , P contractile impulse ( 27 - 32 % , P Mean electromyogram signal amplitude of vastus lateralis was larger in the strength-training than in the st and ard-rehabilitation group at 5 and 12 wk ( P strength training increased muscle mass , maximal isometric strength , RFD , and muscle activation in elderly men and women recovering from long-term muscle disuse and subsequent hip surgery . The improvement in both muscle mass and neural function is likely to have important functional implication s for elderly individuals", "PURPOSE To assess the effects of a one year nutritional supplementation and resistance training program on muscle strength and walking capacity in the elderly . MATERIAL AND METHODS Elderly subjects from two outpatient clinics received a nutritional supplement , that provided 400 Kcal , 15 g/protein and 50 % of vitamin DRVs per day . Half the subjects receiving and not receiving the supplement were r and omly assigned to a resistance exercise training program with two sessions per week . Every six months , body composition using DEXA , limb muscle strength , maximal inspiratory and expiratory pressures and walking capacity were assessed . RESULTS One hundred forty nine subjects were considered eligible and 101 ( 31 supplemented and trained , 28 supplemented , 16 trained and 26 without supplementation nor training ) completed the year of follow up . Overall compliance with the supplement was 48 22 % and trained subjects attended 56 21 % of programmed sessions . No changes in fat free mass were observed in any of the groups , but fat mass increased from 22.5 7.3 to 23.2 7.3 kg in all groups ( p Upper and lower limb strength and walking capacity increased significantly in trained subjects whether supplemented or not . Maximal inspiratory pressure and right h and grip strength increased only in the supplemented and trained group . CONCLUSIONS Resistance training improved muscle strength and walking capacity", "PURPOSE To determine whether isokinetic training can improve the strength of the hemiparetic knee musculature , functional mobility , and physical activity and to evaluate its effect on spasticity in long-term stroke survivors . DESIGN Nonr and omized self-controlled trial . SUBJECTS A volunteer sample of 15 community-dwelling stroke survivors of at least 6 months . INTERVENTION A 6-week ( 3 days/week , 40 minutes/day ) program consisting of warm-up , stretches , reciprocal knee extension and flexion isokinetic strengthening , and cool-down for the paretic limb . MAIN OUTCOME MEASURES Peak isokinetic hamstring and quadriceps torque , quadriceps spasticity , gait velocity , timed Up and Go , timed stair climb , and the Human Activity Profile ( HAP ) scores were recorded at baseline , after training , and 4 weeks after training cessation ( follow-up ) . RESULTS Paretic muscle strength improved after training ( p tone remained consistent ( p > .87 ) . Gait velocity increased after training ( p in stair climbing and timed Up and Go were not significant ( p > .37 ; p > .91 ) , although subjects perceived gains in their physical abilities at follow-up ( p strength and gait velocity without concomitant increases in muscle tone are possible after a short-term strengthening program for stroke survivors . The psychological benefit associated with physical activity is significant", "Background and Purpose — To evaluate the efficacy of supervised high-intensity progressive resistance training ( PRT ) on lower extremity strength , function , and disability in older , long-term stroke survivors . Methods — Forty-two volunteers aged 50 years and above , 6 months to 6 years after a single mild to moderate stroke , were r and omized into either a control group of upper extremity stretching or a PRT group that received a 12-week supervised high-intensity resistance training program consisting of bilateral leg press ( LP ) , unilateral paretic and nonparetic knee extension ( KE ) , ankle dorsiflexion ( DF ) , and plantarflexion ( PF ) exercises . Functional performance was assessed using the 6-minute walk , stair-climb time , repeated chair-rise time , and habitual and maximal gait velocities . Self-reported changes in function and disability were evaluated using the Late Life Function and Disability Instrument ( LLFDI ) . Results — Single-repetition maximum strength significantly improved in the PRT group for LP ( 16.2 % ) , paretic KE ( 31.4 % ) , and nonparetic KE ( 38.2 % ) with no change in the control group . Paretic ankle DF ( 66.7 % versus −24.0 % ) , paretic ankle PF ( 35.5 % versus −20.3 % ) , and nonparetic ankle PF ( 14.7 % versus −13.8 % ) significantly improved in the PRT group compared with the control . The PRT group showed significant improvement in self-reported function and disability with no change in the control . There was no significant difference between groups for any performance-based measure of function . Conclusions — High-intensity PRT improves both paretic and nonparetic lower extremity strength after stroke , and results in reductions in functional limitations and disability", "The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects . Ninety-six subjects , aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less , were r and omized to a resistance training or control group . Trained and control groups were further r and omized to receive in a double blind fashion , vitamin D 400 IU plus 800 mg of calcium per day or calcium alone . Subjects were followed for nine months . Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength , the short physical performance test and timed up and go . The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up , gait speed was higher among subjects supplemented with vitamin ( whether trained or not ) than in non-supplemented subjects ( 838+/-147 and 768+/-127 m/12 min , respectively , p=0.02 ) . Romberg ratio was lower among supplemented controls than non-supplemented trained subjects ( 128+/-40 % and 144+/-37 % , respectively , p=0.05 ) . In conclusion , vitamin D supplementation improved gait speed and body sway , and training improved muscle strength", "PURPOSE The aim of this study was to compare the effects of endurance training alone ( ET ) with combined endurance and strength training ( CT ) on hemodynamic and strength parameters in patients with congestive heart failure ( CHF ) . METHODS Twenty male patients with CHF were r and omized into one of two training regimens consisting of endurance training or a combination of endurance and resistance training . Group ET had 40-min interval cycle ergometer endurance training three times per week . Group CT combined endurance and strength training with the same interval endurance training for 20 min , followed by 20 min of strength training . Left ventricular function was assessed at baseline and after 40 training sessions by echocardiography and radionuclide ventriculography . Work capacity was measured with cardiopulmonary exercise test ( CPX ) and lactate determination . Strength was measured with an isokinetic dynamometer . RESULTS After 40 sessions , the ET group improved functional class , work capacity , peak torque , and muscular endurance . However , peak O2 remained unchanged . Left ventricular ejection fraction ( LVEF ) and fractional shortening ( FS ) decreased , whereas left ventricular end-diastolic diameter ( LVED ) increased . The CT group improved NYHA score , working capacity , peak O2 , and peak lactate ; peak torque and muscular endurance , LVEF , and FS increased , whereas LVED decreased . Compared with ET , CT was significantly ( P improving LV function . CONCLUSION Combined endurance/strength training was superior to endurance training alone concerning improvement of LV function , peak VO2 , and strength parameters . It appears that for stable CHF patients , a greater benefit can be derived from this training modality", "Abstract . There is evidence that high intensity resistance training promotes bone maintenance in older women , however , the effect of high intensity free weight training has not been investigated in older men or women . Furthermore , little is known about the chronic effect of weight training on serum insulin growth factor-I ( IGF-I ) in this population . We compared the effects of a moderate intensity seated resistance-training program with a high intensity st and ing free weight exercise program on bone mass and serum levels of IGF-I and IGFBP3 in healthy older men and women . Twenty-eight men ( 54.6 ± 3.2 years ) and 26 nonestrogen-replaced women ( 52.8 ± 3.3 years ) served as their own controls for 12 weeks , then were r and omly assigned to a moderate or high intensity training group and trained three times/week for 24 weeks . Prior to and after the control period and at the end of training , bone mass and body composition were assessed by dual energy X-ray absorptiometry ( DXA ) , muscle strength by isokinetic dynamometry , muscular power by Wingate Anaerobic Power Test , and IGF-I by radioimmunoassay ( RIA ) . A repeated measures analysis of covariance ( ANCOVA ) revealed that high intensity training result ed in a gain in spine BMD in men ( 1.9 % ) , P increases in trochanteric BMD ( 1.3 % and 2.0 % , respectively ) and a decrease in femoral BMD ( −1.8 % ) . Neither circulating serum IGF-I nor IGFBP3 were altered by either training regimen , but both training programs result ed in improvements in total body strength ( 37.62 % ) and lean mass ( males 4.1 % , females 3.1 % ) . We conclude that although resistance training of moderate to high intensity produced similar muscle changes in older adults , a higher magnitude is necessary to stimulate osteogenesis at the spine . However , at the spine , intensity was not sufficient to offset low levels of estrogen in early postmenopausal women . Furthermore , bone changes were not accompanied by changes in circulating serum levels of IGF-I or IGFBP3", "The plasma levels of dehydroepi and rosterone ( DHEA ) and its sulfated form ( DHEAS ) decline approximately 80 % between the ages of 25 and 75 yr . Muscle mass and strength also decrease with aging . Published data on the effects of DHEA replacement on muscle mass and strength are conflicting . The goals of this study were to determine whether DHEA replacement increases muscle mass and strength and /or enhances the effects of heavy resistance exercise in elderly women and men . We conducted a r and omized , double-blind , placebo-controlled study of the effects of 10 mo of DHEA replacement therapy with the addition of weightlifting exercise training during the last 4 mo of the study ( DHEA + exercise group , n = 29 ; placebo + exercise group , n = 27 ) . DHEA alone for 6 mo did not significantly increase strength or thigh muscle volume . However , DHEA therapy potentiated the effect of 4 mo of weightlifting training on muscle strength , evaluated by means of one-repetition maximum measurement and Cybex dynamometry , and on thigh muscle volume , measured by magnetic resonance imaging . Serum insulin-like growth factor concentration increased in response to DHEA replacement . This study provides evidence that DHEA replacement has the beneficial effect of enhancing the increases in muscle mass and strength induced by heavy resistance exercise in elderly individuals", "The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program ( RT+WLoss ) could maintain bone mineral density ( BMD ) and lean mass compared to moderate weight loss ( WLoss ) alone in older overweight adults with type 2 diabetes . We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program . This was a 12-month trial in which 36 sedentary , overweight adults aged 60 to 80 years with type 2 diabetes were r and omized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months ( phase 1 ) . Thereafter , all participants completed an additional 6-month home-based training without further dietary modification ( phase 2 ) . Total body and regional BMD and bone mineral content ( BMC ) , fat mass ( FM ) and lean mass ( LM ) were assessed by DXA every 6 months . Diet , muscle strength ( 1-RM ) and serum total testosterone , estradiol , SHBG , insulin and IGF-1 were measured every 3 months . No between group differences were detected for changes in any of the hormonal parameters at any measurement point . In phase 1 , after 6 months of gymnasium-based training , weight and FM decreased similarly in both groups ( P Total body BMD and BMC remained unchanged in the RT+WLoss group , but decreased by 0.9 and 1.5 % , respectively , in the WLoss group ( interaction , P femoral neck and lumbar spine ( L2-L4 ) . In phase 2 , after a further 6 months of home-based training , weight and FM increased significantly in both the RT+WLoss ( n=14 ) and WLoss ( n=12 ) group , but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months . These results indicate that in older , overweight adults with type 2 diabetes , dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health", "AIM The aim of the present study was to assess and compare the improvements of muscle strength and power induced by a 16-week resistive programme in a population of 16 older men aged 65 - 81 years . METHODS Training was performed three times per week at an intensity of 80 % of one repetition maximum ( 1RM ) and consisted of both calf raise and leg press exercises . Before- , during- and after-training , maximum isometric and isokinetic torques , maximum power , 1RM , muscle cross-sectional area ( CSA ) and electromyographic activity ( EMG ) of the plantar flexors ( PF ) and knee extensors ( KE ) were examined . RESULTS For the KE and PF , respectively , training result ed in a 29.9 + /- 4.4 % ( mean + /- SE ) and 21.6 + /- 5.4 % increase in 1RM ( P maximum isometric torque , and a 24.1 + /- 6.3 and 33.1 + /- 10.9 % ( P maximum muscle power , calculated from torque-angular velocity curves . The large increase in torque and power was partly accounted by a significant increase in the CSA of the PF ( 5.0 + /- 0.7 % ) and KE ( 7.4 + /- 0.7 % ) , while no significant changes in integrated EMG activity of vastus lateralis and soleus muscles , and in extrapolated maximum shortening velocity were found . After training , a significant increase in torque/CSA ( 10.3 + /- 4 % , P torque , and other factors , such as an increase in individual fibre-specific tension ( in the case of KE ) , a decrease in antagonist muscles ' coactivation , an improved co-ordination and an increased neural drive of the other heads of quadriceps may have contributed to the increments in strength . The significant increase in muscle power seems particularly noteworthy with respect to daily activities involving the displacement of the body over time , namely , the generation of muscle power", " Eighty-six elderly people with limited mobility and dependence in at least one activity of daily living were recruited to a home exercise study . The subjects ( mean age 82 years ) were allocated at r and om to either a strength exercise group , a mobility exercise group or a health education group . Subjects were visited for 30 minutes every 3 - 4 weeks by a physiotherapist who gave both verbal and written instruction . Sixty-nine of the original 86 completed the 6-month study , with five drop-outs from the strength group , ten drop-outs from the mobility group , and two drop-outs from the health education group . By the end of the study , there were no significant differences between the groups with regard to changes in outcome variables . The results showed a trend towards improvement in both the exercise groups in both Sit to St and and Timed Get Up and Go tests , but this failed to attain statistical significance . Further work is required to identify the optimal exercise intervention for this subgroup of the elderly population", "This investigation examined the effect of 6 months of high- or low-intensity resistance exercise on serum homocysteine and lipoprotein ( a ) levels in adults aged 60 - 80 years . Forty-three men and women completed the study protocol . Subjects were r and omly assigned to a control ( n=10 ) , low-intensity ( LEX , n=18 ) , or high-intensity ( HEX , n=15 ) group . Subjects performed 6 months of resistance training at either 50 % of their one-repetition maximum for 13 repetitions ( LEX ) or 80 % of one-repetition maximum for eight repetitions ( HEX ) 3 times per week for 24 weeks . The load was increased by 5 % when their rating of perceived exertion dropped below 18 . One-repetition maximum ; serum homocysteine ; lipoprotein ( a ) ; total and high-density lipoprotein cholesterol ; and dietary intake of vitamins B12 , B6 , and folic acid were measured pre- and post study . Upper and lower body strength significantly ( p Serum homocysteine decreased 5.30 % and 5.34 % for the LEX and HEX groups , respectively ( p lipoprotein ( a ) levels was noted in the control and LEX groups from pre- to post study . No significant differences were noted either pre- or post study for total and high-density lipoprotein cholesterol or any dietary variables . These data indicate that significant reductions in serum levels of homocysteine in the elderly can be derived from resistance exercise training", "PURPOSE To examine the effect of progressive resistance training on muscle function , functional performance , balance , body composition , and muscle thickness in men receiving and rogen deprivation for prostate cancer . METHODS Ten men aged 59 - 82 yr on and rogen deprivation for localized prostate cancer undertook progressive resistance training for 20 wk at 6- to 12-repetition maximum ( RM ) for 12 upper- and lower-body exercises in a university exercise rehabilitation clinic . Outcome measures included muscle strength and muscle endurance for the upper and lower body , functional performance ( repeated chair rise , usual and fast 6-m walk , 6-m backwards walk , stair climb , and 400-m walk time ) , and balance by sensory organization test . Body composition was measured by dual-energy x-ray absorptiometry and muscle thickness at four anatomical sites by B-mode ultrasound . Blood sample s were assessed for prostate specific antigen ( PSA ) , testosterone , growth hormone ( GH ) , cortisol , and hemoglobin . RESULTS Muscle strength ( chest press , 40.5 % ; seated row , 41.9 % ; leg press , 96.3 % ; P muscle endurance ( chest press , 114.9 % ; leg press , 167.1 % ; P 6-m usual walk ( 14.1 % ) , 6-m backwards walk ( 22.3 % ) , chair rise ( 26.8 % ) , stair climbing ( 10.4 % ) , 400-m walk ( 7.4 % ) , and balance ( 7.8 % ) . Muscle thickness increased ( P Whole-body lean mass was preserved with no change in fat mass . There were no significant changes in PSA , testosterone , GH , cortisol , or hemoglobin . CONCLUSIONS Progressive resistance exercise has beneficial effects on muscle strength , functional performance and balance in older men receiving and rogen deprivation for prostate cancer and should be considered to preserve body composition and reduce treatment side effects", "BACKGROUND Exercise programs improve balance , strength and agility in elderly people and thus may prevent falls . However , specific exercise programs that might be widely used in the community and that might be \" prescribed \" by physicians , especially for patients with osteoporosis , have not been evaluated . We conducted a r and omized controlled trial of such a program design ed specifically for women with osteoporosis . METHODS We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise . Women who agreed to participate were r and omly assigned to participate in a twice-weekly exercise class or to not participate in the class . We measured baseline data and , 20 weeks later , changes in static balance ( by dynamic posturography ) , dynamic balance ( by a timed figure-eight run ) and knee extension strength ( by dynamometry ) . RESULTS Of 93 women who began the trial , 80 completed it . Before adjustment for covariates , the intervention group tended to have greater , although nonsignificant , improvements in static balance ( mean difference 4.8 % , 95 % confidence interval [ CI ] -1.3 % to 11.0 % ) , dynamic balance ( mean difference 3.3 % , 95 % CI -1.7 % to 8.4 % ) and knee extension strength ( mean difference 7.8 % , 95 % CI -5.4 % to 21.0 % ) . Mean crude changes in the static balance score were -0.85 ( 95 % CI -2.91 to 1.21 ) for the control group and 1.40 ( 95 % CI -0.66 to 3.46 ) for the intervention group . Mean crude changes in figure-eight velocity ( dynamic balance ) were 0.08 ( 95 % CI 0.02 to 0.14 ) m/s for the control group and 0.14 ( 95 % CI 0.08 to 0.20 ) m/s for the intervention group . For knee extension strength , mean changes were -0.58 ( 95 % CI -3.02 to 1.81 ) kg/m for the control group and 1.03 ( 95 % CI -1.31 to 3.34 ) kg/m for the intervention group . After adjustment for age , physical activity and years of estrogen use , the improvement in dynamic balance was 4.9 % greater for the intervention group than for the control group ( p = 0.044 ) . After adjustment for physical activity , cognitive status and number of fractures ever , the improvement in knee extension strength was 12.8 % greater for the intervention group than for the control group ( p = 0.047 ) . The intervention group also had a 6.3 % greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis , but this difference was not significant ( p = 0.06 ) . INTERPRETATION Relative to controls , participants in the exercise program experienced improvements in dynamic balance and strength , both important determinants of risk for falls , particularly in older women with osteoporosis", "OBJECTIVE To test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis ( OA ) of the knee . METHODS Forty-six community dwelling patients , aged 55 years or older with knee pain and radiographic evidence of knee OA , were r and omized to a 4 month home based progressive strength training program or a nutrition education program ( attention control ) . Thirty-eight patients completed the trial with an adherence of 84 % to the intervention and 65 % to the attention control . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index pain and physical function subscales . Secondary outcomes included clinical knee examination , muscle strength , physical performance measures , and question naires to measure quality of life variables . RESULTS Patients in the strength training group who completed the trial had a 71 % improvement in knee extension strength in the leg reported as most painful versus a 3 % improvement in the control group ( p self-reported pain improved by 36 % and physical function by 38 % in the strength training group versus 11 and 21 % , respectively , in the control group ( p = 0.01 for between group comparison ) . In addition , those patients in the strength training group who completed the trial had a 43 % mean reduction in pain ( p = 0.01 vs controls ) , a 44 % mean improvement in self-reported physical function ( p physical performance , quality of life , and self-efficacy when compared to the control group . CONCLUSION High intensity , home based strength training can produce substantial improvements in strength , pain , physical function and quality of life in patients with knee OA", "Background and aims : The most common cause of accidental injury and death in people over age 65 results from impacts associated with falling . Balance impaired older adults have poorer balance control than healthy young adults or healthy older adults . Lack of sufficient lower extremity strength and inability to rapidly produce muscle force may contribute to diminished balance control in the elderly . This study evaluated the effect of a 10-week high intensity strength- training program targeting key lower extremity muscles for the purpose of improving postural control in frail older adults . Methods : Thirteen experimental and fourteen control subjects , all balance impaired older adults were evaluated in response to unexpected platform perturbations that simulated slips . Results : Following strength training the experimental group was significantly stronger than the control group . Mean ankle moments improved in the experimental group following strength training during forward sway ( Right : p=0.067 , Left : p=0.009 ) and backward sway ( Right : p=0.031 , Left : p=0.058 ) . For the backward sway condition the ankle rate of torque production increased significantly in the experimental group ( Right : p=0.016 , Left : p=0.031 ) . Conclusions : Enhancement of lower extremity strength contributed to improvements in balance stability demonstrated by greater ankle force production , in response to balance threats", "The objectives of this study were to evaluate ( 1 ) the effect of spinal muscle strengthening by loading exercises on the bone mineral density ( BMD ) of the spine , and ( 2 ) the effect of upper extremity loading exercises on the BMD of the midradius and femur in healthy , premenopausal women . The study design was a r and omized , controlled trial of 3 years ' duration . Ninety-six healthy , premenopausal , white women aged 30 - 40 years participated ; 67 completed the study . All subjects were in good health ( normal menses ) and were active , but not athletic ( that is , not involved in a regular sport activity ) . Subjects were r and omized to an exercise or control group . The exercise group performed a supervised , non-strenuous , weight-lifting exercise program . Exercise performance was supervised once a week at the medical facility . In addition , the subjects performed the exercises twice a week on their own . Dietary calcium intake was to be maintained at 1,500 mg/day in both groups . Bone density was measured at the lumbar spine and hip with dual-energy X-ray absorptiometry at 0 , 1 , and 3 years . BMD of the midradius was measured with single photon absorptiometry . Measurements of muscle strength were obtained at baseline and every 3 months for 3 years . Maximal oxygen uptake was measured , and the level of physical activity was recorded . Compliance with the exercise program was excellent during the first year of the study , but decreased thereafter . At the end of 3 years , subject withdrawal was about 34 % from the exercise group and about 22 % from the control group ( total subject withdrawal was about 30 % ) . Muscle strength in the exercise group increased significantly at all involved skeletal sites ( p values all BMD of Ward 's triangle with spinal flexor strength ( r = 0.32 , p = 0.008 ) and with grip strength ( r = 0.38 , p = 0.001 ) . Comparing study groups , we found no significant effect of the loading and nonstrenuous strengthening exercises in the exercise group or free physical activity group ( our control group ) on BMD at the spine , hip , or midradius measurement sites . In active , but not athletic premenopausal women , additional moderate weight-lifting exercises showed no significant effect on BMD", "BACKGROUND Strength training has been shown to be beneficial in older adults . However , very little data exist on the effects of strength training in older diabetics . METHODS 31 community-dwelling older adults with diabetes ( mean age = 66.1 years ) were r and omly assigned to either an exercise ( EX ) or control ( CO ) group . The EX group trained the plantar flexors , knee extensors , knee flexors , hip extensors , and hip flexors muscle groups at 50 % , 60 % , and 70 % of 1-repetition maximum , 2.6 days a week , for 24 months . Mobility tests included the timed up and go , 50-foot walk , and walking up and down 8 stairs . Strength and mobility for both groups were evaluated at 6-month intervals . RESULTS There was a group and time effect as the EX group increased 31.4 % ( p strength for all muscle groups after the first 6 months of training , and the strength gains were retained for the duration of the training intervention . There was also a group and time effect for mobility as performance increased 8.6 % and 9.8 % ( p = .032 and p = 0.031 ) for the first 6 and 12 months , respectively , but decreased to 4.6 % above baseline at the end of the intervention . There were essentially no changes from baseline strength or mobility values for the CO group . CONCLUSION In conclusion , these data suggest that a moderate-intensity resistive-training program can improve mobility and strength for the duration of a 24-month intervention in older adults with diabetes , thus potentially reducing the rate of mobility loss during aging", "PURPOSE This investigation examined the effect of 6 months of high- or low-intensity resistance exercise ( REX ) on bone mineral density ( BMD ) and biochemical markers of bone turnover in adults aged 60 - 83 yr . METHODS Sixty-two men and women ( 68.4 + /- 6 yr ) were stratified for strength and r and omly assigned to a control ( CON , N = 16 ) , low-intensity ( LEX , N = 24 ) , or high-intensity ( HEX , N = 22 ) group . Subjects participated in 6 months of progressive REX training . Subjects trained at either 50 % of their one repetition maximum ( 1-RM ) for 13 repetitions ( LEX ) or 80 % of 1-RM for 8 repetitions ( HEX ) 3 times x wk(-1 ) for 24 wk . One set each of 12 exercises was performed . 1-RM was measured for eight exercises . BMD was measured for total body , femoral neck , and lumbar spine by dual energy x-ray absorptiometry ( DXA ) . Serum levels of bone-specific alkaline phosphatase ( BAP ) , osteocalcin ( OC ) , and pyridinoline cross-links ( PYD ) were measured . RESULTS 1-RM significantly increased for all exercises tested for both the HEX and LEX groups ( P increases in total strength ( sum of all eight 1-RMs ) were 17.2 % and 17.8 % for the LEX and HEX groups , respectively . Bone mineral density ( BMD ) of the femoral neck significantly ( P BMD were found . OC increased by 25.1 % and 39.0 % for the LEX and HEX groups , respectively ( P BAP significantly ( P REX training was successful for improving BMD of the femoral neck in healthy elderly subjects . Also , these data suggest REX increased bone turnover , which over time may lead to further changes in BMD", "PURPOSE This study investigated effects of an 8-wk , low-frequency and low-volume , supervised , progressive strength training program emphasizing free weight , multijoint movements on the muscular power , strength , endurance , and flexibility of African American women 44 to 68 yr of age . METHODS Nineteen sedentary African American women were r and omly assigned to a strength training ( ST ) only group ( N = 12 ; mean age , 51 yr ) or a nonexercise control ( C ) group ( N = 7 ; mean age , 52 yr ) . Maximal power , strength , absolute endurance , and flexibility were assessed before and after training . Subjects trained 2 d x wk(-1 ) using free weight ( barbells and dumbbells ) and machine ( plate loaded ) exercises for two to three sets of 8 to 10 repetitions on both primary and assistance exercises . RESULTS Upper body power ( medicine ball put distance ) significantly increased statistically ( P = 0.002 ) , but gains possibly lacked practical significance because of measurement variation . Lower body power ( peak watts on bicycle ) experienced a small , nonsignificant increase in the ST group . Significant increases ( P = 0.000 ) in 1RM muscle strength occurred in the ST group ( leg press , + 99.8 % ; bench press , + 34.4 % ) . Absolute endurance significantly increased ( P = 0.000 ) in the ST group ( leg press repetitions to failure at 70 % pretest 1RM , + 221 % ; bench press repetitions to failure at 50 % pretest 1RM , + 112 % ) . Significant flexibility gains occurred in the ST group ( sit- and -reach test , + 8.2 % ; P = 0.017 ) . No significant changes occurred in power , strength , absolute endurance , or flexibility in the C group . CONCLUSION This study demonstrates that 8 wk of low-frequency , supervised , progressive strength training emphasizing free weight , multijoint movements can safely cause significant gains in muscle strength , absolute endurance , and flexibility in older African American women", "The expression of two isoforms of insulin-like growth factor-I ( IGF-I ) : mechano growth factor ( MGF ) and IGF-IEa were studied in muscle in response to growth hormone ( GH ) administration with and without resistance training in healthy elderly men . A third isoform , IGF-IEb was also investigated in response to resistance training only . The subjects ( age 74 + /- 1 years , mean + /- S.E.M ) were assigned to either resistance training with placebo , resistance training combined with GH administration or GH administration alone . Real-time quantitative RT-PCR was used to determine mRNA levels in biopsies from the vastus lateralis muscle at baseline , after 5 and 12 weeks in the three groups . GH administration did not change MGF mRNA at 5 weeks , but significantly increased IGF-IEa mRNA ( 237 % ) . After 12 weeks , MGF mRNA was significantly increased ( 80 % ) compared to baseline . Five weeks of resistance training significantly increased the mRNA expression of MGF ( 163 % ) , IGF-IEa ( 68 % ) and IGF-IEb ( 75 % ) . No further changes were observed after 12 weeks . However , after 5 weeks of training combined with GH treatment , MGF mRNA increased significantly ( 456 % ) and IGF-IEa mRNA by ( 167 % ) . No further significant changes were noted at 12 weeks . The data suggest that when mechanical loading in the form of resistance training is combined with GH , MGF mRNA levels are enhanced . This may reflect an overall up-regulation of transcription of the IGF-I gene prior to splicing", "It has been shown that high levels of high-density lipoprotein ( HDL ) cholesterol and low levels of low-density lipoprotein ( LDL ) cholesterol are associated with health maintenance in older women , but the few studies that have examined the relationship between exercise and plasma lipoprotein levels in this elderly population have been equivocal . In addition , there are no studies that examine the plasma lipoprotein response of two different types of exercise in a group of active but nonexercising women . Thus , the effects of exercise training on plasma lipoprotein levels in elderly women remain unclear . The purpose of this research was to examine the effects of endurance and resistance exercise on plasma lipoprotein levels in elderly women who were active but nonexercising prior to the study . A total of 45 healthy , active women , aged 70 - 87 years , were r and omly assigned to either an aerobic training ( AT , 76 + /- 5 years , n = 15 ) , resistance training ( RT , 73 + /- 3 years , n = 15 ) , or control ( C , 74 + /- 5 years , n = 15 ) group . The AT group walked 3 days a week at 70 % heart rate reserve . The duration on day 1 was 20 minutes , and it was increased by 5 minutes each day until subjects were walking for 50 minutes ( week 3 ) . The exercise training session for the RT group consisted of one to three sets of eight repetitions of eight different exercises at an eight repetition maximum ; the C group maintained normal activity . Weight and diet were unchanged across groups . The exercise interventions lasted 10 weeks . Blood sample s were obtained from all subjects at week 0 and week 11 . Training result ed in a significant decrease in 1-mile walk times and heart rate at completion of the walk for the AT group and a significant increase in eight repetition maximum of all RT exercises . Both AT and RT groups experienced increased HDL cholesterol and decreased triglycerides at week 11 compared with week 0 . There were no positive changes in control lipoproteins . Both triglycerides and the total cholesterol to HDL ratio increased significantly while total cholesterol , HDL cholesterol , and LDL cholesterol remained unchanged . The RT group also had significantly lower LDL cholesterol and total cholesterol compared with controls at week 11 . Both RT and endurance training result ed in favorable changes to plasma lipoprotein levels for elderly women in only 10 weeks . The fact that this occurred without concurrent changes in weight or diet is an indication that high-intensity exercise alone can be used to modify lipoproteins in population s of healthy elderly women", "Background : Strength training has been shown to benefit the health and function of older adults . Objective : To investigate whether one set of exercises performed once a week was as effective in increasing muscle strength as training twice a week . Methods : 18 subjects ( 7 women and 11 men ) aged 65–79 years were r and omly assigned to two groups . Both groups performed one set of exercises to muscular fatigue ; group 1 trained 1 day/week and group 2 trained 2 days/week on three lower and three upper body exercises for 9 weeks . The data were analysed using a mixed model 2 × 2 analysis of variance . Results : A significant main effect of time ( p on one-repetition maximum scores was observed . No significant interaction was observed between time and group and therefore no difference in strength changes between training once a week versus twice a week after 9 weeks . Conclusions : One set of exercises performed once weekly to muscle fatigue improved strength as well as twice a week in the older adult . Our results provide information that will assist in design ing strength-training programmes that are more time and cost efficient in producing health and fitness benefits for older adults", "OBJECTIVES To evaluate a dynamic form of weighted vest exercise suitable for home use and design ed to enhance muscle power , balance , and mobility . DESIGN A single-blind , r and omized , controlled trial . SETTING Outpatient exercise research facility situated within an academic long-term care center . PARTICIPANTS Twenty-one community-dwelling women aged 70 and older with a Short Physical Performance Battery ( SPPB ) score between 4 and 10 ( out of 12 ) . INTERVENTIONS Subjects were r and omized into a progressive resistance-training program using weighted vests for resistance with exercises design ed to be specific to mobility tasks and have a component performed at the fastest possible velocity ( Increased Velocity Exercise Specific to Task ( InVEST ) , n=11 ) or a control exercise group ( control , n=10 ) , which performed slow-velocity , low-resistance exercise . Both groups exercised three times a week for 12 weeks . MEASUREMENTS Changes in muscle power , balance , and physical performance were compared . RESULTS In comparison to control group , InVEST group manifested significant improvements ( P leg power across measurements obtained at 75 % to 90 % of the one-repetition maximum . Both groups demonstrated significant improvements in chair st and and SPPB score from baseline , and the InVEST group showed significant improvements in gait speed and chair st and from baseline ( P chair st and time than control ( P leg power and chair rise in this population and is worthy of further investigation as a means of enhancing balance and mobility", "Background and aims : The practice of regular physical exercise has been shown to be effective in slowing the age-related progressive functional deterioration . Most exercise trials have been conducted with supervised training programs . The purpose of this study was to investigate the effectiveness of a 4-month home-based strength training on strength , function and personal satisfaction . Methods : Ten elderly men ( mean age 68.5 years ) were enrolled for home-based training one month after completing a 4-month supervised program ; 12 age-matched men served as the control group . Subjects were asked to perform 3 sessions a week consisting of six resistance exercises with elastic b and s involving the major muscle groups of the upper and lower limbs . We had calculated the correlation between the elongation and resistance of the elastic b and s. The subjects were instructed to keep a diary reporting the execution of the session . We measured dynamic concentric strength of the muscle groups involved in the resistance exercises and maximal isometric strength of the knee extensors and elbow flexors before and after the 4- month home training . The Satisfaction Profile ( SAT-P ) question naire was administered before and one month after the completion of the training program for assessing personal satisfaction . Results : The final to baseline comparison showed a non-significant decrease in mean isometric maximal strength values for knee extensors and elbow flexors in the control group , while the exercise group significantly ( p=0.001 ) improved the average baseline values . Maximal dynamic concentric strength values decreased significantly in the control group , while significant improvements were observed in the exercising subjects . The SAT-P question naire did not show any difference in either group from baseline . The adherence-to- protocol rate based on self-report was 78 % . Conclusions : Home training with elastic b and s appears to be an effective low-cost modality of maintaining strength and function in an elderly population", "BACKGROUND Progressive resistance exercise training ( PRT ) has been shown to increase muscle strength and fat-free mass ( FFM ) in elderly persons . Limited information is available regarding the effects of PRT on lean and fat mass in frail elderly persons . METHODS Ninety-one community-dwelling sedentary men and women , 78 years and older with physical frailty ( defined using st and ardized objective criteria ) were enrolled in a 9-month trial of exercise training ( ET ) . Physical frailty was defined as having 2 of the 3 following criteria : modified Physical Performance Test score between 18 and 32 , peak aerobic power between 10 and 18 ml/kg/min , or self-report of difficulty or assistance with two instrumental activities of daily living or one basic activity of daily living . Participants were r and omly assigned to either a control ( CTL ) group that performed a low intensity home exercise program or a supervised ET group that performed 3 months of low intensity exercise and 3 months of PRT . RESULTS After completion of PRT , ET participants had greater improvements than did CTL participants in maximal voluntary force production for knee extension ( mean Delta + 5.3 + /- 13 ft/lb vs + 1.1 + /- 11 ft/lb , p = .05 ) , measured using isokinetic dynamometry . Total body FFM ( measured using dual energy x-ray absorptiometry ) increased in the ET group , but not in the CTL group ( mean Delta + 0.84 + /- 1.4 kg vs + 0.01 + /- 1.5 kg , p = .005 ) . Total , trunk , intra-abdominal , and subcutaneous fat mass ( measured using dual energy x-ray absorptiometry and (1)H-magnetic resonance imaging ) did not change in response to PRT . CONCLUSIONS Three months of supervised PRT induced improvements in maximal voluntary thigh muscle strength and whole body FFM in frail , community-dwelling elderly women and men . This supervised exercise program may not be sufficient to reduce whole-body or intra-abdominal fat area in this population", "Muscle weakness experienced in old age has many detrimental consequences for activities of daily life . Given the serious problems presented by weakness in old age , strategies to prevent or mitigate this process are of paramount importance . In recent years resistance training has emerged as an effective method for increasing strength in the elderly . Despite this , little is known regarding the muscular , neural and tendinous adaptations that occur with resistance training in old age . Hence , we have conducted a series of experiments to investigate these adaptations . We have found increases in maximal isometric and concentric torque by 9 - 37 % after resistance training in older people ( 65 - 81 years ) . Associated with these strength gains were increases in agonist muscle neural drive without any change in the co-activation of antagonist muscles . Resistance training can cause increases in muscle size and also adaptations to the internal muscle structure . Tendons of older adults adapt to resistance training by increasing their stiffness and Young 's modulus . In conclusion , many of the musculoskeletal factors characterizing ageing can be at least partially mitigated by resistance training", "Sullivan DH , Wall PT , Bariola JR , Bopp MM , Frost YM : Progressive resistance muscle strength training of hospitalized frail elderly . Am J Phys Med Rehabil 2001;80:503–509 . Objective To determine whether frail elderly patients recuperating from acute illnesses could safely participate in and gain appreciable improvement in muscle strength from progressive resistance muscle strength training . Design Muscle strength ( one repetition maximum ) , functional abilities ( sit-to-st and maneuver and 20-sec maximal safe gait speed ) , and body composition were measured before and at the conclusion of a 10-wk program of lower limb progressive resistance muscle strength training . The nonr and omized study was conducted in a 30-bed geriatric rehabilitation unit of a university-affiliated Veterans Affairs hospital and a 28-bed transitional care unit of a community nursing home . Participants included 19 recuperating elderly subjects ( 14 male , 5 female ; 13 ambulatory , 6 nonambulatory ) > 64 yr ( mean age , 82.8 ± 7.9 yr ) . Results The one repetition maximum increased an average of 74 % ± 49 % ( median , 70 % ; interquartile range , 38%–95 % , and an average of 20 ± 13 kg ( P = 0.0001 ) . Sit-to-st and maneuver times improved in 15 of 19 cases ( 79 % ) . Maximum safe gait speeds improved in 10 of 19 cases ( 53 % ) . Four of the six nonambulatory subjects progressed to ambulatory status . No subject experienced a complication . Conclusions A carefully monitored program of progressive resistance muscle strength training to regain muscle strength is a safe and possibly effective method for frail elderly recuperating from acute illnesses . A r and omized control study is needed to examine the degree to which progressive resistance muscle strength training offers advantages , if any , over routine posthospital care that includes traditional low-intensity physical therapy", "PURPOSE To compare the effects of the 16-wk training period ( 2 d.wk(-1 ) ) of resistance training alone ( S ) , endurance training alone ( E ) , or combined resistance ( once weekly ) and endurance ( once weekly ) training ( SE ) on muscle mass , maximal strength and power of the leg and arm extensor muscles , and maximal workload ( Wmax ) by using a incremental cycling test in older men . METHODS Thirty-one healthy men ( 65 - 74 yr ) were divided into three treatment groups to train 2x wk(-1 ) for 16 wk : S ( N = 10 ) , E ( N = 11 ) , or SE ( N = 10 ; 1x wk(-1 ) S + 1x wk(-1 ) E ) . The subjects were tested at 8-wk intervals ( i.e. , weeks 8 and 16 ) . RESULTS There were no significant differences between S- and SE-induced muscle hypertrophy ( 11 % and 11 % ) and maximal strength ( 41 % and 38 % ) gains of the legs as well as between E- and SE-induced Wmax ( 28 % and 23 % ) gains . The increase in arm strength in S ( 36 % ) was greater than that recorded in SE ( 22 % ) and greater than that recorded in E ( 0 % ) . CONCLUSIONS Prolonged combined resistance and endurance training in older men seemed to lead to similar gains in muscle mass , maximal strength , and power of the legs as resistance training alone and to similar gains in maximal peak power output measured in an incremental cycling test as endurance training alone . These findings may have an effect on how resistance exercise is prescribed to older adults ", "Purpose . To investigate feasibility and effectiveness of an individually-directed , group strength-training programme on knee muscle strength after stroke . Method . Ten volunteers ( 62 ± 11 years , mean ± SD ) , 6 – 12 months after first-ever unilateral stroke , walking independently with or without aids were recruited . Using an A1-B-A2 design , 3 sets of baseline measures were taken at 2 weekly intervals ; volunteers then attended twice weekly sessions of low intensity progressive strengthening exercises and were assessed after each series of 8 sessions to a maximum of 24 sessions ; post training , measures were repeated after 4 – 6 weeks . Measures included isometric and concentric knee extensor muscle strength and 10 m walking velocity . Results . Strength of knee extensor muscles was improved after training ( ANOVA , p training , isometric strength increased by 58 ± 19 % and concentric strength at 30 ° /s by 51 ± 14 % ; walking velocity quickened from 0.47 ± 0.06 m · s−1 to 0.57 ± 0.08 m · s−1 ( t = −3.31 , p of low intensity strength training after stroke and confirm published evidence . It was feasible for one therapist to deliver the training programmes for 4 – 6 participants at a time ; an important feature when re sources are limited", "OBJECTIVE To determine the effect on balance and strength of 3 months of intensive balance and /or weight training followed by 6 months of low intensity Tai Chi training for maintenance of gains . DESIGN R and omized control intervention . Four groups in 2 x 2 design : Control , Balance , Strength , Balance + Strength , using blinded testers . SETTING Exercise and balance laboratory at University of Connecticut Health Center . PARTICIPANTS Subjects were 110 healthy community dwellers ( mean age 80 ) who were free of dementia , neurological disease , and serious cardiovascular or musculoskeletal conditions . INTERVENTIONS Short-term training ( 3 months ) occurred 3 times/week ( 45 minutes Balance and Strength , 90 minutes Balance + Strength ) . Balance training included equilibrium control exercises of firm and foam surfaces and center-of-pressure biofeedback . Strengthening consisted of lower extremity weight-lifting . All subjects than received long-term group Tai Chi instruction ( 6 months , 1 hour , 1 time/week ) . MEASUREMENTS Losses of balance during Sensory Organization Testing ( LOB ) , single stance time ( SST ) , voluntary limits of stability ( FBOS ) , summed isokinetic torque of eight lower extremity movements ( ISOK ) , and usual gait velocity ( GVU ) . RESULTS AND CONCLUSIONS Balance training meaningfully improved all balance measures by restoring performance to a level analogous to an individual 3 to 10 years younger : LOB = -2.0 + /- 0.3 ( adjusted paired differences , P ISOK by 1.1 + /- 0.1 Nm kg-1 ( P Tai Chi , although there was some decrement", "The effect that aerobic ( AT ) and /or strength training ( ST ) has on altering peak aerobic power ( VO2peak ) , muscle strength , left ventricular ( LV ) morphology , and diastolic filling in healthy older women is not known . We assessed the effects of 12 weeks of AT , ST , combined aerobic and strength training ( COMT ) , or no training ( NT ) on VO2peak , muscle strength , LV morphology , and diastolic filling in 31 healthy women ( 68 + /- 4 years ) . Relative VO2peak was significantly greater after 12 weeks of AT , ST , or COMT . Upper and lower extremity strength were significantly higher after 12 weeks of ST or COMT with no change after AT or NT . LV morphology and diastolic filling were not altered after 12 weeks of AT , ST , COMT , or NT . Twelve weeks of ST or COMT are as effective as 12 weeks of AT for increasing relative VO2peak , however , ST and COMT are more effective than AT for improving overall muscle strength", "Chronic heart failure ( CHF ) is characterized by a skeletal muscle myopathy not optimally addressed by current treatment paradigms or aerobic exercise . Sixteen older women with CHF were compared with 80 age-matched peers without CHF and r and omized to progressive resistance training or control stretching exercises for 10 wk . Women with CHF had significantly lower muscle strength ( P aerobic capacity to women without CHF . Exercise training was well tolerated and result ed in no changes in resting cardiac indexes in CHF patients . Strength improved by an average of 43.4 + /- 8.8 % in resistance trainers vs. -1.7 + /- 2.8 % in controls ( P = 0.001 ) , muscle endurance by 299 + /- 66 % vs. 1 + /- 3 % ( P = 0.001 ) , and 6-min walk distance by 49 + /- 14 m ( 13 % ) vs. -3 + /- 19 m ( -3 % ) ( P = 0.03 ) . Increases in type I fiber area ( 9.5 + /- 16 % ) and citrate synthase activity ( 35 + /- 21 % ) in skeletal muscle were independently predictive of improved 6-min walk distance ( r2 = 0.78 ; P = 0.0024 ) . High-intensity progressive resistance training improves impaired skeletal muscle characteristics and overall exercise performance in older women with CHF . These gains are largely explained by skeletal muscle and not resting cardiac adaptations", "The purpose of this study was to investigate the efficacy of , and the adherence to , a 12-week home-based progressive resistance training program for older adults utilizing elastic tubing . Sixty-two adults ( mean age , 71.2 years ) qualified to participate in the study . Subjects were r and omly assigned to either the exercise ( E ) ( n=31 ) or non-exercise ( NE ) group ( n=31 ) . Pre- and post-testing included isokinetic ( 1.05 rad · s −1 ) concentric/eccentric knee extension/flexion strength testing and flexibility measures of the hip , knee , and ankle . The E group trained three times per week , performing one to three sets of 10–12 repetitions for each of 12 resistance exercises . The exercises involved muscles of both the lower and upper body . Within the E group , 25 of the 31 subjects ( 80.6 % ) completed the study . Of the E subjects completing the study adherence to the three training sessions per week was 90 % ( range 72%–100 % ) . Training resistances used during workouts increased significantly with the average estimated increase being 82 % ( P P . No other significant changes were observed between E and NE groups . These results suggest that home-based resistance training programs utilizing elastic tubing can serve as a practical and effective means of eliciting strength gains in adults over the age of 65", "PURPOSE To determine the effect of a 12-month moderate resistance training program on phenotypic and functional immunological parameters of previously sedentary , clinical ly healthy , elderly women . METHODS A total of 42 clinical ly healthy , sedentary females ( aged 60 - 77 yr old ) were r and omly assigned to either a moderate-intensity resistance training program or a control group during a 12-month longitudinal , r and omized , controlled , intervention study . Resistance training program consisted of three sets of 12 repetitions at 54.9 + /- 2.4 % 1RM for five different exercises performed three times per week during 12 months . Natural killer cell cytotoxic activity ( NKCA ) , lymphoproliferative response to the mitogen phytohemaglutinin ( PHA ) , and quantification of the lymphocytes ( CD3 , CD3CD19 , CD56 ) and sub population s ( CD4 , CD8 , CD56 , CD56 ) as well as cellular expression molecules ( CD25 , CD28 , CD45RA , CD45RO , CD69 , CD95 , HLA-DR ) were determined by immunological assays . RESULTS The experimental group increased muscle strength in 44 % and 48 % after 6 and 12 months , respectively ( P time for quantitative ( CD3 , CD3CD19 , CD56 , CD4 , CD8 , CD45RA , CD45RO , CD56 , CD56 , CD95 , CD28 , CD25 , CD69 , HLA-DR ) and functional immunological parameters ( natural killer cell cytotoxic activity and lymphoproliferative response ) . CONCLUSION A 12-month moderate resistance training program increases muscle strength , but it does not change immune phenotypic and functional parameters of previously sedentary , clinical ly healthy , elderly women", " The effects of endurance training on exercise capacity and health-related quality of life ( HRQL ) in chronic obstructive pulmonary disease ( COPD ) patients have been studied thoroughly , while resistance training has been rarely evaluated . This study investigated the effects of resistance training in comparison with endurance training in patients with moderate to severe COPD and peripheral muscle weakness ( isometric knee extension peak torque ) . Forty-eight patients ( age 64±8 yrs , forced expiratory volume in one second 38±17 % pred ) were r and omly assigned to resistance training ( RT , n=24 ) or endurance training ( ET , n=24 ) . The former consisted of dynamic strengthening exercises . The latter consisted of walking , cycling and arm cranking . Respiratory and peripheral muscle force , exercise capacity , and HRQL were re-evaluated in all patients who completed the 12-week rehabilitation ( RT n=14 , ET n=16 ) . Statistically significant increases in knee extension peak torque ( RT 20±21 % , ET 42±21 % ) , maximal knee flexion force ( RT 31±39 % , ET 28±37 % ) , elbow flexion force ( RT 24±19 % , ET 33±25 % ) , 6-min walking distance ( 6MWD ) ( RT 79±74 m , ET 95±57 m ) , maximum workload ( RT 15±16 Watt , ET 14±13 Watt ) and HRQL ( RT 16±25 points , ET 16±15 points ) were observed . No significant differences in changes in HRQL and 6MWD were seen between the two treatments . Resistance training and endurance training have similar effects on peripheral muscle force , exercise capacity and health-related quality of life in chronic obstructive pulmonary disease patients with peripheral muscle weakness", "Women aged 67 - 84 yr were r and omly assigned to either resistance exercise ( RE , n = 15 ) or control group ( C , n = 14 ) . RE group completed 10 wk of resistance training , whereas C group maintained normal activity . Blood sample s were obtained from the RE group ( at the same time points as for resting C ) at rest , immediately after resistance exercise , and 2 h after exercise before ( week 0 ) and after ( week 10 ) training . Mononuclear cell ( CD3 + , CD3+CD4 + , CD3+CD8 + , CD19 + , and CD3-CD16+CD56 + ) number , lymphocyte proliferative ( LP ) response to mitogen , natural cell-mediated cytotoxicity ( NCMC ) , and serum cortisol levels were determined . Strength increased significantly in RE subjects ( % change 8-repetition maximum = 148 % ) . No significant group , exercise time , or training effects were found for CD3 + , CD3+CD4 + , or CD3+CD8 + cells , but there was a significant exercise time effect for CD3-CD16+CD56 + cells . LP response was not different between groups , across exercise time , or after training . NCMC was increased immediately after exercise for RE subjects at week 0 and for RE and C groups at week 10 . The week 0 and week 10 NCMC values were above baseline for both RE and C groups 2 h after exercise . In conclusion , acute resistance exercise did not result in postexercise suppression of NCMC or LP , and 10 wk of resistance training did not influence resting immune measures in women aged 67 - 84 yr", "Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels", "BACKGROUND The aim of the present study was to compare the changes in voluntary strength ( isometric , concentric , and eccentric ) and functional mobility in response to maximal isokinetic eccentric-only resistance training to those elicited by maximal isometric-only or maximal isokinetic concentric-only resistance training in older adults . METHODS Twelve women ( 73 + /- 7 years ) and 18 men ( 73 + /- 5 years ) completed a 12-week training program ( three times per week ) using a Biodex System 3 dynamometer . Primary outcome measures included peak isometric and isokinetic ( concentric and eccentric ) knee extensor strength , concentric work , concentric power , stair ascent and descent , and gait speed . Participants were r and omly assigned to one of three training groups : isometric-only , isokinetic concentric-only , or isokinetic eccentric-only . RESULTS All three training groups demonstrated an increase in peak isometric and isokinetic concentric and eccentric strength following 12 weeks of training ( p Step time was positively influenced ( p gait speed was unchanged following 12 weeks of training . All three training groups experienced a significant increase in peak concentric work and concentric power ( p peak concentric work and concentric power when compared to the isometric and eccentric training groups . CONCLUSIONS It was clear that all three resistance training programs ( isometric , concentric , and eccentric ) in older adults were effective in increasing strength , concentric work , and concentric power over the 12-week training period . Furthermore , 12 weeks of resistance training result ed in improved stair ascent and descent performance", "OBJECTIVE To examine the effect of high-intensity progressive resistance training combined with moderate weight loss on glycemic control and body composition in older patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Sedentary , overweight men and women with type 2 diabetes , aged 60 - 80 years ( n = 36 ) , were r and omized to high-intensity progressive resistance training plus moderate weight loss ( RT & WL group ) or moderate weight loss plus a control program ( WL group ) . Clinical and laboratory measurements were assessed at 0 , 3 , and 6 months . RESULTS HbA(1c ) fell significantly more in RT & WL than WL at 3 months ( 0.6 + /- 0.7 vs. 0.07 + /- 0.8 % , P body weight ( RT & WL 2.5 + /- 2.9 vs. WL 3.1 + /- 2.1 kg ) and fat mass ( RT & WL 2.4 + /- 2.7 vs. WL 2.7 + /- 2.5 kg ) were observed after 6 months . In contrast , lean body mass ( LBM ) increased in the RT & WL group ( 0.5 + /- 1.1 kg ) and decreased in the WL group ( 0.4 + /- 1.0 ) after 6 months ( P fasting glucose , insulin , serum lipids and lipoproteins , or resting blood pressure . CONCLUSIONS High-intensity progressive resistance training , in combination with moderate weight loss , was effective in improving glycemic control in older patients with type 2 diabetes . Additional benefits of improved muscular strength and LBM identify high-intensity resistance training as a feasible and effective component in the management program for older patients with type 2 diabetes", "Physical activity energy expenditure ( PAEE ) is a determinant of prognosis and fitness in older patients with coronary heart disease ( CHD ) . PAEE and total energy expenditure ( TEE ) are closely related to fatness , physical function , and metabolic risk in older individuals . The goal of this study was to assess effects of resistance training on PAEE , TEE , and fitness in older women with chronic CHD and physical activity limitations ( N = 51 , mean age : 72 + 5 yr ) . The study intervention consisted of a progressive , 6-mo program of resistance training vs. a control group condition of low-intensity yoga and deep breathing . The study interventions were completed by 42 of the 51 participants . The intervention group manifested a 177 + /- 213 kcal/day ( + 9 % ) increase in TEE , pre- to posttraining , measured by the doubly labeled water technique during a nonexercise 10-day period ( P resting metabolic rate measured by indirect calorimetry ( P PAEE ( P upper and lower body strength , but no change in fat-free mass , measured by dual X-ray absorptiometry , or left ventricular function , measured by echocardiography and Doppler . Women in the control group showed no alterations in TEE or its determinants . There were no changes between groups in body composition , aerobic capacity , or measures of mental depression . These results demonstrate that resistance training of 6-mo duration leads to an increase in TEE and PAEE in older women with chronic CHD", "BACKGROUND Muscle size and strength decrease with aging , and the result ant muscle weakness has been implicated in increased risk of falls in older adults . These falls have large economic and functional costs . METHODS The purpose of this r and omized , controlled study was to determine if an 8-week , 3-day per week intense ( 77.8 + /- 3.4 % of 1-repetition maximum [ 1RM ] ) strength training program could improve functional ability related to the risk of falling in subjects aged 61 - -87 years ( mean 72 , SD 6.3 ) . Twelve strength-training-naive subjects performed two sets of 10 repetitions for six lower body exercises while 12 subjects served as nonintervention controls . Subjects were tested pre- , mid- , and postintervention for strength gain and on three tests of functional ability . RESULTS Postintervention strength was significantly better ( p injuries were reported as a result of either training or 1RM testing . After controlling for preintervention differences , repeated measure analysis of covariance ( ANCOVA ) found a significant difference between experimental and nonintervention control subjects for postintervention maximal walking speed [ F(1,19 ) = 5.03 , p 1-leg blind balance time or 5-repetition sit-to-st and performance [ F(1,19 ) = .082 ; F(1,19 ) = .068 , respectively , p > .05 ] . CONCLUSIONS These findings suggest that strength training alone does not appear to enhance st and ing balance or sit-to-st and performance in active , community-dwelling older adults but that it may improve maximal walking speed . The relationship between strength gain and risk of falls remains unclear . The data do reinforce the notion that intense strength training is a safe and effective way to increase muscle strength in this population", "Cycling on a mechanically braked cycle ergometer was used as a novel approach to compare the effects of three different 16-wk resistance-training programs on isometric force , power output , and selected functional abilities in 31 healthy 65- to 74-yr-old women . Training was conducted three times per week . During each session , individuals of the speed group performed 8 sets of 16 pedal revolutions at 40 % of the maximal resistance to complete two revolutions ( 2 RM ) ; strength group performed 8 sets of 8 revolutions at 80 % of 2 RM ; and combination group performed 4 sets of 16 revolutions at 40 % and 4 sets of 8 revolutions at 80 % of 2 RM . During each set , all participants were required to pedal as fast as possible with a 2-min interval between sets . All training groups significantly increased force , power , and functional abilities ( maximal treadmill walking speed , vertical jumping , and box stepping ) at week 8 ( in the range from 6.5 to 20.8 % ) with no further improvement at week 16 ( except maximal treadmill walking speed ) , but no significant differences were observed between the three groups . The novel approach to performing both low- and high-resistance training , based on the use of a cycle ergometer , has been shown to be effective in improving strength , power , and functional abilities in a group of healthy women . Even fit older women can still improve in functional abilities . Interestingly , the \" high-speed \" and \" low-speed \" programs induced an increase in both power and strength of similar magnitude", "BACKGROUND The beneficial role of exercise in improving bone mineral density , muscle strength and balance , has been documented predominantly in younger population s. These findings may not apply to elderly population s with limited ability to perform exercises of high intensity . OBJECTIVE To examine the effects of Tai Chi ( TC ) and resistance exercise ( RTE ) on bone mineral density ( BMD ) , muscle strength , balance and flexibility in community living elderly people . DESIGN R and omised controlled trial , using blocked r and omization with stratification by sex . SETTING A community in the New Territories Region of Hong Kong , China . SUBJECTS One hundred eighty subjects ( 90 men , 90 women ) aged 65 - 74 , were recruited through advertisements in community centres . METHODS Subjects were assigned to participate in TC , RTE three times a week , or no intervention ( C ) for 12 months . Measurements were carried out at baseline , 6 and 12 months . Analyses of covariance ( ANCOVA ) adjusted for age , and baseline values of variables that were significantly different between groups : i.e. smoking and flexibility for men ; quadriceps strength for women . RESULTS Compliance was high ( TC 81 % , RTE 76 % ) . In women , both TC and RTE groups had less BMD loss at total hip compared with controls . No effect was observed in men . No difference in either balance , flexibility or the number of falls was observed between either intervention or controls after 12 months . CONCLUSION The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes", "BACKGROUND Loss of muscle power due to normal aging has greater functional impact than loss of strength alone . The present study compared two resistance training programs , one aim ed at enhancing muscle power and one at increasing muscle strength , on muscle function and functional performance in older adults . METHODS Sixty-seven healthy , independent older adults ( 65 - 84 years ) were r and omized to a high-velocity varied resistance ( HV ) , constant resistance ( ST ) , or nontraining control ( CO ) group . Participants trained twice weekly for 24 weeks using six exercises . Dynamic and isometric muscle strength , muscle power , movement velocity , muscle endurance , and a battery of functional performance tasks were assessed . Secondary outcomes included body composition , quality of life , and balance confidence . RESULTS Muscle strength increased significantly ( p Peak muscle power also increased with training ( p peak power was 50.5 + /- 4.1 % , 33.8 + /- 3.8 % , and -2.5 + /- 3.9 % in the HV , ST , and CO groups , respectively . Training also improved selected functional performance tasks in the HV and ST groups compared to controls ( p quality of life ( p = .018 ) . CONCLUSION Muscle power and muscle strength improved similarly using either resistance training protocol , and these changes were accompanied by improvements in several functional performance tasks . However , improvements in the HV group occurred with less total work performed per training session", "BACKGROUND The purpose of this efficacy study was to measure the dose-response effect of a free weight-based resistance training program by comparing the effects of two training intensities ( low-moderate and high ) of the knee extensor ( KE ) muscles on muscle function , functional limitations , and self-reported disability . METHODS The authors conducted a single-blinded , r and omized , placebo-controlled trial . Twenty-two institutionalized elders ( mean age , 81.5 years ) were assigned to either high-intensity strength training ( HI ; n = 8) , low-moderate intensity strength training ( LI ; n = 6 ) , or weight-free placebo-control training ( PC ; n = 8) . The HI group trained at 80 % of their 1-repetition maximum and the LI group trained at 40 % . All groups performed 3 sets of 8 repetitions , 3 times per week for 10 weeks . Outcome measures included KE maximal strength , KE endurance , and functional performance as assessed by 6-minute walking , chair-rising , and stair-climbing tests , and by self-reported disability . RESULTS KE strength and endurance , stair-climbing power , and chair-rising time improved significantly in the HI and LI groups compared with the PC group . Six-minute walking distance improved significantly in the HI group but not in the LI group compared with the PC group . Changes observed in HI were significantly different from those observed in the LI group for KE strength and endurance and the 6-minute walking test , with a trend in the same direction for chair-rising and stair-climbing . Changes in strength were significantly related to changes in functional outcomes , explaining 37 % to 61 % of the variance . CONCLUSIONS These results show strong dose-response relationships between resistance training intensity and strength gains , and between strength gains and functional improvements after resistance training . Low-moderate intensity resistance training of the KE muscles may not be sufficiently robust from a physiologic perspective to achieve optimal improvement of functional performance . Supervised HI , free weight-based training for frail elders appears to be as safe as lower intensity training but is more effective physiologically and functionally", "The present study deals with the question whether 24-week strength training alters neuromechanical properties of plantar flexors in elderly people ( 73–83 years ) . The first purpose of the present study was to evaluate the effect of strength training on musculotendinous ( MT ) stiffness of the triceps surae ( TS ) . The training was performed twice per week and mainly consisted of three series of ten repetitions of calf-rise and leg-press exercises at 75 % of the three-repetition maximum . Using quick-release movements at different levels of submaximal torques performed measurements of MT stiffness . Surface electromyograms ( EMG ) of each part of the TS and the tibialis anterior were also recorded . A stiffness index ( SI ) , defined as the slope of the angular stiffness – torque relationship ( SIMT-Torque ) , was used to quantify changes in MT stiffness . Results showed a significant decrease in SIMT-Torque by 25.2 % following training ( P neural mechanism has influences on this decrease . Therefore , an activation SI , defined as the slope of the angular stiffness – EMG relationship ( SIMT-EMG ) was used to overcome the influence of changes in agonist activity , and thus to quantify changes in MT intrinsic elastic properties . SIMT-EMG only decreased by 11.2 % following training ( P that MT stiffness decreases following training in elderly individuals , counterbalancing the effect of ageing . These changes seem not only to be due to peripheral but also to neural adaptations", "OBJECTIVE To examine the effects of an 8-week home-based resistance exercise program on balance , power , and mobility in adults with multiple sclerosis . DESIGN Experimental group design . SETTING General community . PARTICIPANTS Twenty-nine women ( age , 50.3+/-8.5 y ) and 8 men ( age , 51.1+/-7.1 y ) were stratified by disability level and age and were r and omized into exercise ( n=19 ) and control ( n=17 ) groups . INTERVENTION The exercise group had lower-extremity resistance training 3 times a week . The control group maintained current level of physical activity . Main outcome measures Primary outcome measures included balance , as measured by anteroposterior sway , mediolateral sway , and sway velocity using the AccuSway(PLUS ) force platform ; mobility as assessed with the Up and Go test ; and leg power as assessed with the Leg Extensor Power Rig . RESULTS Leg extensor power improved significantly in the exercise group ( pretest , 3.19+/-1.36 W/kg ; posttest , 3.95+/-1.23 W/kg ; P=.004 ) , although measures of balance and mobility did not change . CONCLUSIONS The home-based resistance program was well tolerated by participants and offered a practical means to improve leg extensor power in a short period of time", "OBJECTIVES The objective of this study is to determine if exercise increases joint symptoms in older adults with a history of arthritis or produces symptoms in older adults without such history . In addition , we examine whether joint symptoms explain the large observed variation in strength gain in older adults undergoing vigorous strength training exercise , and report the incidence of musculoskeletal injuries upon initiation of an exercise program . DESIGN A population -based , single blinded , r and omized controlled trial with three exercise groups and one control group . SETTING A large urban health maintenance organization . PARTICIPANTS Older men and women ( N = 105 ) aged 68 to 85 , with leg strength below the 50th percentile for their age , sex , height , and weight and without neuromuscular disease or active cardiovascular disease . INTERVENTIONS Supervised exercise in 1-hour sessions , three times each week , for 24 to 26 weeks . One exercise group did strength training ( ST ) using weight machines ( n = 25 ) ; another group did endurance training ( ET ) using stationary cycles ( n = 25 ) ; and the third group did combined strength training and endurance training ( ST+ET ) ( n = 25 ) . The control group ( n = 30 ) received no intervention . MEASUREMENTS Strength was measured at the ankle , knee , hip , and elbow using an isokinetic dynamometer . Joint symptoms were rated on a 6-point scale ( 0 = none , 5 = severe ) . Arthritis severity was based on self-reported use of arthritis medication . Health status was measured with subscales of the SF-36 and Sickness Impact Profile ( SIP ) . RESULTS Joint symptoms fluctuated over time in all exercise groups , but they did not improve or worsen significantly in any group . The physical dimension of the SIP and SF-36 subscale scores , including Bodily Pain Scores , did not change over time in any group . Subjects with arthritis and joint symptoms gained as much strength with strength training as did subjects without joint symptoms . Adjustment for age , gender , baseline strength , adherence , and exercise group did not affect this finding . The rate of minor musculoskeletal injuries was 2.2 injuries per 1000 exercise hours . CONCLUSIONS Moderate intensity stationary cycle exercise and vigorous intensity strength training do not appear to produce or exacerbate joint symptoms in older adults . Joint symptoms did not explain the large variation in gains in strength in older adults participating in a st and ardized strength training exercise program . Musculoskeletal injuries occurred relatively infrequently , and no major injuries occurred . In evaluating joint pain that occurs in older adults in well regulated exercise programs , clinicians should consider other etiologies before attributing pain to exercise per se", "PURPOSE The purpose of this study was to compare the effects of high-resistance ( HR ) training , 3 times.wk(-1 ) at 80 % maximum strength ( 1RM ) with 3 times.wk(-1 ) variable-resistance ( VR ) training ( once-weekly training at 80 % , 65 % , and 50 % 1RM ) in older adults . METHODS The study was a 6-month resistance training intervention conducted in the Birmingham Alabama metropolitan area , and included healthy volunteer men and women over the age of 60 . Twenty-eight subjects were assigned r and omly to two training groups . Eight volunteers served as controls . Before and after 25 wk of training , body composition was measured by densitometry ; strength by isometric tests ; and difficulty in performing daily activity tasks ( DAT ) by measuring heart rate , oxygen uptake , electromyography , and perceived exertion . In addition , 1RM strength was measured every 25 d throughout the 6 months of training . Repeated measures ANOVA and paired t-tests with Bonferroni corrections for additive alpha were used to analyze the data . RESULTS The control group did not significantly change in any study parameter . No significant change in body weight occurred for any group . However , the HR and VR groups increased fat free mass ( FFM ) similarly ( 1.8 kg and 1.9 kg , respectively ) . Both training groups increased strength significantly , without significant differences in change . No significant change in oxygen uptake occurred during DAT . However , there was a significant time effect for heart rate and perceived exertion . Greater decrease in normalized integrated electromyography during the carry task was found in the VR group over the HR and control groups . CONCLUSION Despite similar increases in strength and fat free mass , the VR group decreased difficulty of performing the carry task more than the HR group . These data suggest that larger improvements in DAT may be achieved if frequency of high-resistance training is less than 3 times.wk(-1 )", "OBJECTIVES To compare high intensity strength training with weightlifting exercises or with elastic b and s. SETTING Outpatient unit of cardiac rehabilitation . TYPE : Prospect i ve r and omised clinical trial . POPULATION Inclusion of coronary patients in phase II after medical or surgical treatment of a myocardiac infa rct ion , without cardiac insufficiency ; beta-blockers were accepted . METHOD Evaluation of coronary patients at beginning and at the end of a 4 week cardiac rehabilitation program . It included progressive aerobic training according to Karvonen method for all the patients , associated with weightlifting exercises ( Koch press ) in the control group , or use of elastic b and s in the experimental group . Cardiac rate , oxygen consumption at rest and at maximum power were the main criteria with also muscle strength of quadriceps , hamstrings , biceps brachii , latissimus dorsi and triceps brachii , body mass indexes , quality of life with SF-36 , anxiety ( stay T test ) and perceived exertion with the Borg 10-point category-ratio scale , myotendinous injuries ( Shaw scale ) . RESULTS Twenty-six coronary patients , all male from 45 to 65 years old , all receiving beta-blockers , were included , 13 in each group . Control and experimental groups were initially similar . At the end of the 4 week program , all the two groups improved significantly their strength and power and there were no differences between the two groups . Perceived exertion was lower in the group using elastic b and s and there were no myotendinous lesions . CONCLUSION Strength training with elastic b and s is a low-cost , attractive , playful technique , proposed to a group of coronary patients , which appears as effective in cardiac rehabilitation as individual weightlifting training", "BACKGROUND Resistance training has been introduced in cardiac rehabilitation to give more benefit than traditional training . Haemodynamic evaluation of cardiac patients to resistance training has generally consisted of continuous HR monitoring and discontinuous blood pressure measurements . DESIGN AND METHODS Blood pressure ( BP ) and heart rate ( HR ) responses to resistance training were evaluated using continuous monitoring ( Finapres ) during low ( four sets of 17 repetitions at 40 % of the one-repetition maximum strength [ 1-RM ] ) and high intensity resistance training ( four sets of 10 repetitions at 70 % of 1-RM ) on a leg extension machine in 14 patients who participated in a rehabilitation programme . Work volume was identical in the low- and high-level resistance training . RESULTS The HR and systolic blood pressure ( SBP ) during low intensity resistance training were always larger than during high intensity ( P Peak SBP increased from set 1 to set 3 and 4 during both low and high intensity resistance training ( P Peak HR was larger in set 4 ( 95+/-11 bpm ) than in set 1 only during low intensity resistance training ( 91+/-12 bpm ) ( P HR and SBP during both low and high intensity modalities . CONCLUSIONS The SBP and HR responses to resistance training are related to the duration of exercise . Sets with Blood pressure should be measured during the last repetitions of the exercise set", "BACKGROUND The study tested the effect of strength and endurance training on gait , balance , physical health status , fall risk , and health services use in older adults . METHODS The study was a single-blinded , r and omized controlled trial with intention-to-treat analysis . Adults ( n = 105 ) age 68 - 85 with at least mild deficits in strength and balance were selected from a r and om sample of enrollees in a health maintenance organization . The intervention was supervised exercise ( 1-h sessions , three per week , for 24 - 26 weeks ) , followed by self-supervised exercise . Exercise groups included strength training using weight machines ( n = 25 ) , endurance training using bicycles ( n = 25 ) , and strength and endurance training ( n = 25 ) . Study outcomes included gait tests , balance tests , physical health status measures , self-reported falls ( up to 25 months of follow-up ) , and inpatient and outpatient use and costs . RESULTS There were no effects of exercise on gait , balance , or physical health status . Exercise had a protective effect on risk of falling ( relative hazard = .53 , 95 % CI = .30-.91 ) . Between 7 and 18 months after r and omization , control subjects had more outpatient clinic visits ( p hospital costs over $ 5000 ( p Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults . In community-living adults with mainly mild impairments in gait , balance , and physical health status , short-term exercise may not have a restorative effect on these impairments", "OBJECTIVE To determine the safety and efficacy of 3 months of resistive training of multiple lower extremity muscle groups compared with balance training in persons over 75 years . DESIGN R and omized 3-month clinical trial . Subjects ( n = 110 , mean age 80 ) were r and omized to 4 groups in a 2 x 2 design ( control , resistive , balance , combined resistive/balance ) . INTERVENTIONS Resistive training involved knee extension and flexion , hip abduction and extension , and plantar and dorsiflexion using simple resistive machines and s and bags . Balance training consisted of exercises to improve postural control . The control group attended 5 health-related discussion sessions . MEASUREMENTS Summed isokinetic moments ( N m ) of 8 leg movements : hip , knee and ankle flexion/extension , and hip abduction/adduction . Secondary outcomes were gait velocity and chair rise time . MAIN RESULTS Summed peak moment increased in both resistive exercise-trained groups ( 13 % increase in the resistive group and 21 % in the combined training group , P resistance training was significant ( MANOVA F = 21.1 , P strength , and there was no interaction ( positive or negative ) between balance and resistive training . Maximal gait velocity and chair rise time did not improve . Eleven subjects ( 20 % ) had musculoskeletal complaints related to resistive training , but all were able to complete the program with modifications . CONCLUSION Resistive training using simple equipment is an effective and acceptable method to increase overall leg strength in older persons . Resistive or balance training did not improve maximal gait velocity or chair rise time in this sample of relatively healthy older persons", "The purpose of the study was to determine whether resistance training ( RT ) or a combination of resistance and aerobic training ( CT ) result ed in the most improvement in measures of functional ability in functionally limited elders . Elderly adults who exhibited some limits in functional ability were r and omly assigned to either a CT , RT , or control ( C ) group . Both RT and CT exercised three times per week for 16 weeks . At Weeks 0 and 17 , participants completed six measures of strength and six functional tests . A 3 ( group ) x 3 ( time ) ANOVA with repeated measures on the time factor was used to analyze the results . CT and RT scored significantly better than C at Week 17 for biceps curl , elbow extension , chair st and , and time up the stairs . These findings demonstrate that RT and CT are both effective at increasing measures of strength and functional ability in elderly adults who begin exercise with functional limitations", "OBJECTIVE To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women . DESIGN R and omized controlled trial of 1-year duration . SETTING Exercise laboratory at Tufts University , Boston , Mass. POPULATION Forty postmenopausal white women , 50 to 70 years of age , participated in the study ; 39 women completed the study . The subjects were sedentary and estrogen-deplete . INTERVENTIONS High-intensity strength training exercises 2 days per week using five different exercises ( n = 20 ) vs untreated controls ( n = 19 ) . MAIN OUTCOME MEASURES Dual energy x-ray absorptiometry for bone status , one repetition maximum for muscle strength , 24-hour urinary creatinine for muscle mass , and backward t and em walk for dynamic balance . RESULTS Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 + /- 0.039 g/cm2 ( 0.9 % + /- 4.5 % ) ( mean + /- SD ) and 0.009 + /- 0.033 g/cm2 ( 1.0 % + /- 3.6 % ) , respectively , in the strength-trained women and decreased by -0.022 + /- 0.035 g/cm2 ( -2.5 % + /- 3.8 % ) and -0.019 + /- 0.035 g/cm2 ( -1.8 % + /- 3.5 % ) , respectively , in the controls ( P = .02 and .04 ) . Total body bone mineral content was preserved in the strength-trained women ( + 2.0 + /- 68 g ; 0.0 % + /- 3.0 % ) and tended to decrease in the controls ( -33 + 77 g ; -1.2 % + /- 3.4 % , P = .12 ) . Muscle mass , muscle strength , and dynamic balance increased in the strength-trained women and decreased in the controls ( P = .03 to High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass , strength , and balance in postmenopausal women", "INTRODUCTION Prior investigations in post-myocardial infa rct ion and healthy elderly subjects have established that heart rate variability ( HRV ) predicts mortality . Predominantly cross-sectional studies have shown an association between endurance training and measures of HRV . In a r and omized trial , this study sought to prospect ively compare the effects of endurance and strength training on HRV in 45 healthy elderly females ( average age 69.9 + /- 0.9 years ) . METHODS All subjects were rigorously screened to be normal by history , physical , blood tests , ECG , ETT and echocardiogram . All subjects were monitored for 24 hours by a 2-channel Holter before and after training . Artifacts and arrhythmias were manually removed . Tapes were examined for st and ard measures of HRV . INTERVENTION 15 subjects were r and omized to endurance trained ( ET ) , 15 subjects to strength training ( ST ) , and 15 subjects to no training ( NT ) for six months . RESULTS Training result ed in a significant increase in VO2max in the ET ( + 7.4 % , p = 0.005 ) group only . There was a small but not significant decrease in HR with both the ET and ST groups . ET result ed in a significant increase in most time domain and all frequency domain measures of HRV . ST result ed in no significant change in HRV measures . CONCLUSION Strength training , as opposed to endurance training has no significant impact on HRV . This suggests that exercise interventions design ed to improve strength ( such as weight-lifting ) will have little to no impact on HRV , suggesting that aerobic and strength training operate through different mechanisms to reduce cardiac risk", "The purpose of this study was to determine the effects of a 12-month resistance training program , of two different intensities , on bone mineral density ( BMD ) in healthy , older women . Twenty-six Caucasian women ( aged 65 - 79 years ) completed the study . Subjects were r and omly assigned to one of three groups : high-intensity ( HI ; n = 8) , low-intensity ( LI ; n = 7 ) , and control ( CON ; n = 11 ) . The active groups performed 10 exercises , 3 days/week under supervision . Exercise intensity was maintained at 80 % of one-repetition maximum ( 1-RM ) for the HI groups , and at 40 % 1-RM for the LI group . The volume of work was maintained constant between the two groups by assigning the LI group twice as many repetitions for each exercise . Maximal muscular strength and BMD of the lumbar spine and total hip were measured at baseline and at 12 months . Strength was evaluated using the 1-RM method , and BMD was determined by dual-energy X-ray absorptiometry . Exercise session attendance was similar for the two groups ( 81.0 % HI ; 76.8 % LI ) . Muscular strength improved in the exercisers compared with the CON group ( p Percentage change in lumbar spine BMD was 0.7 + /- 1.9 % , 0.5 + /- 2.4 % , and -0.1 + /- 2.3 % for the HI , LI , and CON groups , respectively . Percentage change in total hip BMD was 0.8 + /- 2.3 % ( HI ) , 1.0 + /- 1.7 % ( LI ) , and 0.9 + /- 1.3 % ( CON ) . Group differences in BMD change were not significant ( p > 0.05 ) . These findings suggest that high-intensity and low-intensity resistance training regimens effectively increase muscular strength , but not lumbar spine or total hip BMD , in healthy , older women", "This study assessed the effect of resistive training ( RT ) , with or without highdose chromium picolinate ( Cr-pic ) supplementation , on body composition and skeletal muscle size of older women . Seventeen sedentary women , age range 54 - 71 years , BMI 28.8 + /- 2.4 kg/m2 , were r and omly assigned ( double-blind ) to groups ( Cr-pic , n = 9 ; Placebo , n = 8) that consumed either 924 micrograms Cr/d as Cr-pic or a low-Cr placebo ( RT program ( 2 day/week , 3 sets.exercise-1.d-1 , 80 % of 1 repetition maximum ) . Urinary chromium excretion was 60-fold higher in the Cr-pic group , compared to the Placebo group ( p maximal strength of the muscle groups trained by 8 to 34 % ( p Cr-pic supplementation . Percent body fat and fat-free mass were unchanged with RT in these weight-stable women , independent of Cr-pic supplementation . Type I and type II muscle fiber areas of the m. vastus lateralis were not changed over time and were not influenced by Cr-pic supplementation . These data demonstrate that high-dose Cr-pic supplementation did not increase maximal strength above that of resistive training alone in older women . Further , these data show that , under these experimental conditions , whole body composition and skeletal muscle size were not significantly changed due to resistive training and were not influenced by supplemental chromium picolinate", "INTRODUCTION The aim of this study was to establish the value of physical training as a treatment of reduced physical ability in frail , elderly patients living at home . MATERIAL AND METHODS 46 community-dwelling frail elderly patients ( > 74 years ) participated in a r and omised , controlled intervention study . The intervention group was transported to training , whilst the control group was not activated . All had their physical functional ability determined using SF-36 , Berg 's Balance Scale , 10 m walking test and muscle strength test . RESULTS The intervention group had a significant improvement in functional ability measured by means of Berg 's Balance Scale , walking test , muscle strength test and SF-36 ( p average cost per patient was estimated at 121 DKK per training session , equivalent to 1452 DKK for a 12-week training period . DISCUSSION The establishing of a \" multi-component-training \" as a treatment offer , to which general practitioners could refer their patients , would involve some costs , but savings due to reduced nursing care can be expected", "OBJECTIVE To examine the effects of aerobic and resistance exercise on self-efficacy beliefs in older adults with knee osteoarthritis ( OA ) and to determine whether self-efficacy and knee pain mediated the effects of the treatments on stair time performance and health perceptions . METHODS Measures of self-efficacy , knee pain , stair climbing performance , and health perceptions were collected prior to r and omization and again at an 18-month followup in older adults with knee OA who were assigned to 1 of 3 treatment conditions : aerobic exercise , resistance training , or health education control . All analyses were conducted on the intention-to-treat principle . RESULTS Both exercise treatments increased self-efficacy for stair climbing in comparison to the health education control group . Both knee pain and self-efficacy mediated the effect of the treatments on stair climb time , whereas only knee pain mediated health perceptions . CONCLUSIONS The findings suggest that control beliefs and changes in physical symptoms such as knee pain are important outcomes in physical activity programs with patients who have OA of the knee . Moreover , these variables mediate the effects that such programs have on disability and health perceptions", "Exercise is known to preserve many physiological responses in the healthy elderly , yet those with physical impairments are often discouraged from exercising . The authors studied the effects of a closely supervised exercise program design ed specifically for elders with health problems and functional limitations . Tests , selected for their relevance to clinical patient management , included the Self Evaluation of Life Function question naire , treadmill performance , and tests of autonomic nervous system and neuromotor functions . Ambulatory volunteers , aged 64 to 83 years , with noncardiac health problems , were r and omly assigned to a control group ( CG ; n = 17 ) or a 16-week exercise group ( EG ; 3 hr/wk , n = 18 ) . Nine of the control and 13 of the exercise subjects completed the study . All EG dropouts were due to illness . EG attendance averaged 87 % , and subjects trained at a heart rate ( HR ) of 103 + /- 5 beats/min ( SD ) ( 98 % of prescription HR ) . Though EG test responses showed a tendency to improve , none reached statistical significance . This result was affected by the small number completing the study and the variability inherent in such a sample . Though these impaired elderly subjects enthusiastically and safely participated with high attendance and at an exercise intensity adequate to expect benefit , measurable training effects were not demonstrated", "OBJECTIVE This 8 week r and omized , double blind clinical trial compared the effect of a combined home based progressive exercise program and treatment with the nonsteroidal medication oxaprozin to treatment with oxaprozin alone on pain and physical functioning in older community dwelling patients with unilateral knee osteoarthritis ( OA ) . METHODS Efficacy variables measured before and after 8 weeks included ( 1 ) pain using the Western Ontario McMaster ( WOMAC ) pain , physical disability , and stiffness subscales and a 10 point visual analog scale ( VAS ) before and after self-paced walking ( SPW ) and stepping ( SPS ) functional tasks ; ( 2 ) physical function using the time to complete a self-paced 40 m walk ( SPW ) and 20 cycles of 2 steps ( SPS ) : ( 3 ) physical activity level using the Physical Activity Scale for Elderly ( PASE ) ; ( 4 ) clinical measures of knee functioning ( range of motion ) . One hundred seventy-nine men and women ( mean age 74 + /- 6 yrs ) with radiographic evidence of mild/moderate medial compartment OA were r and omized to either a progressive home based knee exercise program ( n = 88 ) or a control program ( n = 89 ) . All patients were given oxaprozin 1,200 mg per os daily . RESULTS We observed significant reduction from baseline in activity related pain ( VAS ) ; and improvement in SPW and SPS test time , passive range of motion , and PASE after 8 weeks in both groups . These changes were significantly greater ( p progressive exercise program to nonsteroidal antiinflammatory therapy in patients with knee OA can improve measures of activity and activity related pain more than medication alone", "This study tested whether moderate resistance training would improve femoral bone mineral density ( BMD ) in long-term users of hormone therapy with low BMD . The study was a 2-year r and omized , controlled , trial ( RCT ) of moderate resistance training of either the lower extremity or the upper extremity . Eighty-five women participated in a 6-month observation period . The setting was center-based and home-based training . The participants were 189 women aged 59–78 years , with total femur T-scores from −0.8 to −2.8 and on hormone therapy ( HT ) for a minimum of 2 years ( mean 11.8 years ) ; 153 completed the trial . Lower extremity training used weight belts ( mean 7.8 kg ) in step-ups and chair rises ; upper extremity training used elastic b and s and dumbbells . Measurements were BMD and body composition [ dual-energy X-ray absorptiometry ( DXA ) ] , bone turnover markers . Total femoral BMD showed a downward trend during the observation period : 0.35%±0.18 % ( P=0.14 ) . The response to training was similar in the upper and lower groups in the primary outcomes . At 2 years , total femoral BMD increased 1.5 % ( 95 % CI 0.8%–2.2 % ) in the lower group and 1.8 % ( 95 % CI 1.1%–2.5 % ) in the upper group . Trochanter BMD increased 2.4 % ( 95 % CI 1.3%–3.5 % ) in the lower group and 2.5 % ( 95 % CI 1.4%–3.6 % ) in the upper group ( for both analyses time effect P 1 year , a bone resorption marker ( C-telopeptide ) decreased 9 % ( P=0.04 ) . Bone formation markers , bone-specific alkaline phosphatase , decreased 5 % ( P ) , and N-terminal type I procollagen peptide decreased 7 % ( P=0.01 ) . Body composition ( percent lean and percent body fat ) was maintained in both groups . We concluded that long-term moderate resistance training reversed bone loss , decreased bone turnover , increased femur BMD , and maintained body composition . The similarity of response in upper and lower groups supports a systemic response rather than a site-specific response to moderate resistance training", "When frail older people become acutely ill , they are at increased risk of further functional deterioration and rehabilitation is needed to restore functioning . The effects of an out-patient multicomponent training program including strength training after hospitalization were studied in a r and omized controlled trial . Sixty-eight women ( mean age 83.0 + /- 3.9 years ) who were hospitalized due to an acute illness and were mobility impaired at admission were r and omized into training ( N = 34 ) and home exercise ( N = 34 ) groups . Maximal voluntary isometric strength of knee extension and hip abduction , dynamic balance , and maximal walking speed were measured before and after the 10-week training period , and 3 and 9 months after the end of the intervention . After the intervention , significant improvements were observed in the training group compared to the home exercise group in the maximal voluntary isometric knee extension strength ( 20.8 % vs. 5.1 % , P= 0.009 ) , balance scale ( + 4.4 points vs. -1.3 points , P= 0.001 ) and walking speed ( + 0.12 m s-1 vs. -0.05 m s-1 , P= 0.022 ) . Effects on knee extension and hip abduction strength , balance and walking speed were observed 3 months later , and some effects on hip abduction strength ( 9.0 % vs. -11.8 % , P= 0.004 ) and mobility were still apparent even 9 months after the intervention", "Abstract . This study examined the effects of 6 months of resistance exercise ( RX ) on basal and post-aerobic exercise lipid peroxidation ( LIPOX ) . Men and women [ n=62 , mean ( SD ) age 68.4 ( 6 ) years ] were divided r and omly into either a control ( n=16 , CON ) , low-intensity training [ LEX n=24 ; 50 % one-repetition maximum ( 1RM ) , 13 repetitions/exercise ] , or high-intensity training ( HEX n=22 , 80 % 1RM , 8 repetitions/exercise ) group . Pre- and post-training , subjects performed a grade d aerobic exercise test ( GXT ) . Blood sample s were collected prior to and 10 min following each GXT . Subjects trained 3 times per week for 6 months using 12 RX machines . LIPOX was determined by measuring levels of thiobarbituric reactive acid substances ( TBARS ) and lipid hydroperoxides ( PEROX ) . RX had no effect on resting LIPOX . Post-training , post-GXT TBARS were lower in the LEX and HEX groups by 14 % and 18 % , respectively , compared to CON ( P Post-GXT PEROX levels were lower ( P Serum total and non-protein ( glutathione ) thiols were higher in the LEX and HEX groups following training compared to CON ( P serum LIPOX , ( 2 ) provide protection against oxidizing agents in vitro , and ( 3 ) provide a \" cross-protection \" against the oxidative stress generated by aerobic exercise , perhaps mediated by improvements in the thiol portion of the antioxidant defense", "OBJECTIVE To determine the short- and long-term effects of resistance training on muscle strength , psychological well-being , control-beliefs , cognitive speed and memory in normally active elderly people . METHODS 46 elderly people ( mean age 73.2 years ; 18 women and 28 men ) , were r and omly assigned to training and control groups ( n=23 each ) . Pre- and post-tests were administered 1 week before and 1 week after the 8-week training intervention . The training sessions , performed once a week , consisted of a 10 min warm-up phase and eight resistance exercises on machines . RESULTS There was a significant increase in maximum dynamic strength in the training group . This training effect was associated with a significant decrease in self-attentiveness , which is known to enhance psychological well-being . No significant changes could be observed in control-beliefs . Modest effects on cognitive functioning occurred with the training procedure : although there were no changes in cognitive speed , significant pre/post-changes could be shown in free recall and recognition in the experimental group . A post-test comparison between the experimental group and control group showed a weak effect for recognition but no significant differences in free recall . Significant long-term effects were found in the training group for muscular strength and memory performance ( free recall ) 1 year later . CONCLUSION An 8-week programme of resistance training lessens anxiety and self-attentiveness and improves muscle strength", "To evaluate the effect of aerobic and variable resistance exercise training on fractionated reaction time ( RT ) and speed of movement ( SM ) in elderly individuals , premotor time ( PMT ) , motor time ( MT ) , total RT , and SM were measured in 49 healthy , untrained men and women , 70 to 79 years of age , before and after 6 months of training . Subjects were r and omized into either a walk/jog ( n = 17 ) , a strength training ( n = 20 ) , or a control group ( n = 12 ) . Improvements in aerobic capacity were only weakly related to reduced total RT ( r = 0.30 , p less than .05 ) . Analysis of covariance revealed that there were no differences ( p greater than .05 ) among the three groups after training with respect to PMT , MT , total RT , and SM . These findings indicate that 6 months of aerobic and strength training did not induce significant changes in RT or SM in this group", "BACKGROUND Decreased muscle strength impedes elders ' functional performance in daily activities such as gait . The mechanisms whereby increased strength improves gait are unknown . METHODS A prospect i ve , blinded , r and omized trial of moderate intensity strength exercise was conducted and its impact was measured on functional mobility during gait in 132 functionally limited elders . Lower extremity strength was measured , including hip abductor , hip extensor , and knee extensor strength . Of the 132 subjects , 120 subjects ( mean age , 75.1 yrs ) completed 6 months of elastic b and resistance training at least 3 times a week or served as no-exercise controls . RESULTS Subjects increased their lower extremity strength in the exercise and control groups , by 17.6 % and 7.3 % ( p Gait stability improved significantly more in the exercise group than in the control group ( p forward gait velocity were not significantly different between groups . Peak mediolateral velocity and base of support improved in the exercise group , but not in the control group . Change in lower extremity strength correlated significantly but weakly with many of the gait variables . CONCLUSIONS Gait stability , especially mediolateral steadiness , improved in the exercise group but not in the control group . These results show that even moderate strength gains benefit gait performance in elders and thus provide a sound basis for encouraging low-intensity strength training for elders with functional limitations", "Resistance training ( RT ) has gained popularity as an effective form of exercise for older adults . However , the effects of RT on left ventricular ( LV ) morphology and systolic function in older persons is not well known . The purpose of this study was to assess the effects of 16 weeks of RT on LV morphology and systolic function in healthy older men . Subjects were r and omly assigned into a RT group ( n = 10 ; mean+/- SD age , 68 + /- 3 years ) or a nonexercise control group ( n = 10 ; age 68 + /- 4 years ) . RT was performed 3 times per week for 16 weeks at a mean intensity between 60 % and 80 % of 1 repetition maximum . Leg and bench press 1 repetition maximum and 2-dimensional echocardiography were performed at baseline and after 4 , 8 , 12 , and 16 weeks of training in the RT group . Sixteen weeks of RT was associated with an increase in leg press maximal strength ( baseline , 285 + /- 48 kg ; after 16 weeks , 367 + /- 47 kg ; p bench press maximal strength ( baseline , 59 + /- 11 kg ; after 16 weeks , 69 + /- 11 kg ; p leg press maximal strength ( baseline , 291 + /- 59 kg ; after 16 weeks , 290 + /- 53 kg ; p > 0.05 ) or bench press maximal strength ( baseline , 60 + /- 9 kg ; after 16 weeks , 61 + /- 13 kg ; p > .05 ) was found in control subjects during the same time . RT was not associated with changes in LV cavity size , wall thickness , mass , or systolic function after 4 , 8 , 12 , and 16 weeks of exercise . Thus , 16 weeks of RT was sufficient to increase leg press and bench press maximal strength but did not alter the size or systolic function of the senescent left ventricle", "UNLABELLED The increase in blood pressure during training is a disadvantage of strength training in the elderly . To reduce this effect it is generally recommended to apply lower levels of relative muscle strength with longer contraction duration s or higher number of repetitions ( continuous mode ( CM ) , e. g. 50 % of maximal strength , 10 to 15 repetitions without pauses ) . Alternatively , higher contraction forces could be combined with frequent periods of muscle relaxation and fewer repetitions ( intermittent mode ( IM ) , e. g. 80 % of maximal strength , 8 repetitions consisting of 1.5 s concentric contraction , 1.5 s eccentric contraction and 3 s pause ) . We compared the blood pressure effects of both approaches during leg press exercise in two age groups ( 10 subjects aged 22 to 42 y , 9 subjects aged 60 to 72 y ) . Blood pressure was measured continuously by a non-invasive method ( FINAPRES , Ohmeda 2300 , Englewood USA ) . RESULTS 1 . The age of the subjects had no significant influence on the slopes of blood pressure increase during the different exercise modes . 2 . The frequent insertion of short ( 3 s ) periods of muscle relaxation ( IM ) decreased the blood pressure response more effectively than a reduction in contraction strength alone ( CM ) . Short muscle relaxations have an immediate , mechanical effect on blood pressure and they allow a metabolic recovery which attenuates the trend of blood pressure increase", "BACKGROUND Resistance exercise training was applied to patients with chronic heart failure ( CHF ) on the basis that it may partly reverse deficiencies in skeletal muscle strength and endurance , aerobic power ( VO(2peak ) ) , heart rate variability ( HRV ) , and forearm blood flow ( FBF ) that are all putative factors in the syndrome . METHODS AND RESULTS Thirty-nine CHF patients ( New York Heart Association Functional Class=2.3+/-0.5 ; left ventricular ejection fraction 28%+/-7 % ; age 65+/-11 years ; 33:6 male : female ) underwent 2 identical series of tests , 1 week apart , for strength and endurance of the knee and elbow extensors and flexors , VO(2peak ) , HRV , FBF at rest , and FBF activated by forearm exercise or limb ischemia . Patients were then r and omized to 3 months of resistance training ( EX , n=19 ) , consisting of mainly isokinetic ( hydraulic ) ergometry , interspersed with rest intervals , or continuance with usual care ( CON , n=20 ) , after which they underwent repeat endpoint testing . Combining all 4 movement patterns , strength increased for EX by 21+/-30 % ( mean+/-SD , P endurance improved 21+/-21 % ( P CON remained almost unchanged ( strength P VO(2peak ) improved in EX by 11+/-15 % ( P ratio of low-frequency to high-frequency spectral power fell after resistance training in EX by 44+/-53 % ( P FBF increased at rest by 20+/-32 % ( P limb ischemia ( 26+/-45 % , P EX , but not in CON ( P resistance exercise training in CHF patients produced favorable changes to skeletal muscle strength and endurance , VO(2peak ) , FBF , and HRV", "Purpose . Despite clear evidence of physiological declines during detraining , the effects of detraining on functional performance and quality of life have not often been investigated . The purpose of this study was to investigate functional performance and quality of life measures after a training and detraining programme with community-dwelling elderly . Method . Twenty-three subjects took part in a combined programme of muscle strengthening and aerobic conditioning twice a week and were assessed at baseline , after training , and after one , two , and three months of detraining . Functional performance was assessed by gait speed and by the rate of ascending and descending stairs , while quality of life was evaluated by the Nottingham Health Profile . Results . Repeated measures ANOVA showed that gains observed in measures of gait speed , ascending , and descending stairs returned to baseline after one , two , and three months of detraining , respectively . However , the gains in quality of life remained unchanged . Conclusions . One-month detraining was enough to show functional decline , with gait speed the most sensitive parameter to detect these changes and QL measure most resilient , beneficial factor during the detraining process . Based on these findings , it is recommended that programmes devised for elderly should not be interrupted , to maintain the acquired benefits", "The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Forty-five patients with moderate to severe COPD were r and omized to 12 wk of aerobic training alone ( AERO ) or combined with strength training ( AERO + ST ) . The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle , and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises . Measurements of peripheral muscle strength , thigh muscle cross-sectional area ( MCSA ) by computed tomographic scanning , maximal exercise capacity , 6-min walking distance ( 6MWD ) , and quality of life with the chronic respiratory question naire were obtained at baseline and after training . Thirty-six patients completed the program and constituted the study group . The strength of the quadriceps femoris increased significantly in both groups ( p thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 + /- 13 % and 15 + /- 9 % , respectively ( p 0.05 ) . These changes were significantly different in the two study groups ( p increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups . The changes in peak exercise work rate , 6MWD , and quality of life were comparable in the two groups . In conclusion , the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass , but does not provide additional improvement in exercise capacity or quality of life", "OBJECTIVES To determine whether exercise training added to ongoing hormone replacement therapy ( HRT ) increases bone mineral density ( BMD ) in physically frail elderly women . DESIGN Prospect i ve controlled trial . SETTING University-based research center . PARTICIPANTS Twenty-eight women on HRT , aged 75 and older with physical frailty . INTERVENTIONS Participants were assigned to 9 months of supervised ( EXER ) or home ( HOME ) exercise . The EXER program started with physical therapy and gradually incorporated resistance and endurance training . The HOME program consisted of flexibility exercises . MEASUREMENTS Changes in BMD and body composition . RESULTS There were larger increases in lumbar spine BMD in response to EXER than with HOME ( 3.5 % vs 1.5 % , P = .048 ) , with a trend for larger increases in total body BMD ( 1.5 % vs 0.2 % , P = .058 ) . There were no significant between-group differences in hip BMD . The EXER group had decreases in weight ( -2.2 + /- 0.3 kg , P = .010 ) and fat mass ( -2.7 + /- 0.4 kg , P = .018 ) and increases in muscle strength ( 9 - 30 % , P physically frail elderly women on HRT , relatively vigorous exercise training significantly increased lumbar spine BMD . The improved BMD and strength in response to exercise could reduce fracture risk in frail women already on HRT", "The short- and long-term effects of heavy-resistance training ( 85 % of one-repetition maximum ( RM ) ) on elbow flexion and knee extension dynamic and isokinetic strength and on morphology in the biceps brachii and vastus lateralis muscles were evaluated during 1 year in 35 Sc and inavian men and women , aged 70 - 77 years , 12 of whom formed a control group . After the first 11 weeks of training ( n = 23 ; 3 times/week ) elbow flexion and knee extension dynamic strength ( 1 RM ) had increased [ mean + /- SD ] 49 % + /- 16 and 163 % + /- 75 , respectively , with no significant difference between men and women . For the following 27 weeks , strength was maintained with one training session per week ( n = 12 ) but dropped without training ( n = 11 ) . After the final 11 weeks of training ( n = 11 ; 3 times/week ) , strength had further increased 32 % + /- 16 in both the arm and the leg . Isokinetic strength measurements ( Cybex II ; 30 degrees/s ) revealed similar but smaller gains than for dynamic strength . Muscle biopsies ( n = 20 ) taken at the start and after the first 11 weeks of training showed a significant increase in the area of both type 1 and type 2 fibers in the biceps brachii muscle and a positive significant correlation between the percentage increase in the proportional area of type 2 fibers in the vastus lateralis muscle and the percentage increase in knee extension dynamic muscle strength . In conclusion , older Sc and inavian men and women have a high capacity both to improve and to maintain muscle strength , some of which is mediated through an adaptation in the muscle fiber type population", "This study examines and compares the effect of aerobic and resistance exercise on emotional and physical function among older persons with initially high or low depressive symptomatology . Data are from the Fitness , Arthritis and Seniors Trial , a trial among 439 persons 60 years or older with knee osteoarthritis r and omized to health education ( control ) , resistance exercise , or aerobic exercise groups . Depressive symptoms ( assessed by the Center for Epidemiologic Studies --Depression scale ) and physical function ( disability , walking speed , and pain ) were assessed at baseline and after 3 , 9 , and 18 months . Compared with results for the control group , aerobic exercise significantly lowered depressive symptoms over time . No such effect was observed for resistance exercise . The reduction in depressive symptoms with aerobic exercise was found both among the 98 participants with initially high depressive symptomatology and among the 340 participants with initially low depressive symptomatology and was the strongest for the most compliant persons . Aerobic and resistance exercise significantly reduced disability and pain and increased walking speed both , and to an equal extent , in persons with high depressive symptomatology and persons with low depressive symptomatology", "The short-term effects of an accessible exercise intervention on the strength and health-related quality of life ( HRQOL ) among older adult women were evaluated . We conducted an 8-week resistance training intervention utilizing elastic b and s in 62 community-dwelling women with a mean age of 68 years . Participants were r and omly assigned to either an exercise or a control group . Pre- and postintervention assessment s included strength tests and HRQOL . Results revealed significant increases in three major muscles compared to the control group . However , there were no significant changes on either mental or physical health functioning . The elastic b and s provide older adult women with an inexpensive , practical exercise program that effectively increases strength within 8 weeks but may have little effect on self-reported HRQOL", "The aim of the study was to examine the effects of a maximal resistance training following the principles of the most effective resistance training known from sport adapted to elderly people . Twenty-four subjects were r and omly assigned into a training group ( 10 females and 4 males , age ; 76.2 + /- 3.2 years ) that underwent a training program and a control group ( 6 females and 4 males , age ; 76.6 + /- 2.7 years ) that did not participate in the training program . Before and after the training period , both groups were identically examined ( blood and urine sample , spiroergometric testing , morphological measurements ) . The training group underwent a 12-week training program . Eight different exercises for the largest muscle groups of the largest joints were defined as one training circle . Training took place twice a week and commenced with two training circles per week ( one circle per training session ) . After every four weeks , one training circle per week was added until four training circles per week were reached . Before , after every four weeks ( changes in training amount ) and after the training period , the maximum strength was measured . Data was analysed by the independent T-test and the analysis of variance , in case of significance , the dependent T-test and the Scheffé-test were used . In the resistance training group , the fat-free body mass was increased by approximately 2.9 + /- 0.5 kg , with no significant difference between females and males . Ergometrical fitness was increased by approximately 15 % , while the maximum oxygen uptake was increased by approximately 12 % . Maximum strength was increased between 26 % ( bench pull ) and 38 % ( leg press ) . Resistance training that consisted of two training sessions per week was found to be at least as efficient as resistance training that included three training sessions per week , provided that the number of sets performed were equal . Seventy-five-year-old females were found to have a significantly higher body fat content than males of the same age ( 37 % versus 26 % , respectively ) . However , the decrease in body fat mass due to resistance training was found to be equal in both females and males ( - 4 + /- 0.8 kg ) . Furthermore , there was almost no difference in muscle strength between the sexes for this age group ( for example ; leg press : females 86 kg versus males 82 kg )", "Both aerobic training ( AT ) and resistance training ( RT ) may increase aerobic power ( VO2peak ) in the older population ; however , the role of changes in the capillary supply in this response has not been evaluated . Twenty healthy men ( age 65 - 74 yr ) engaged in either 9 wk of lower body RT followed by 9 wk of AT on a cycle ergometer ( RT-->AT group ) or 18 wk of AT on a cycle ergometer ( AT-->AT group ) . RT was performed three times per week and consisted of three sets of four exercises at 6 - 12 repetitions maximum . AT was performed three times per week for 30 min at 60 - 70 % heart rate reserve . VO2peak was increased after both RT and AT ( P number of capillaries per fiber perimeter length was increased after both AT and RT ( P VO2peak , whereas capillary density was increased only after AT ( P change in capillary supply and VO2peak ( r = 0.52 ) , suggest the possibility that similar mechanisms may be involved in the increase of VO2peak after high-intensity RT and AT in the older population", "OBJECTIVES To evaluate weighted stair climbing exercise ( SCE ) as a means of increasing lower extremity muscle power in mobility-limited older people . DESIGN Single-blinded , r and omized controlled pilot study . SETTING Human physiology laboratory of a metropolitan university . PARTICIPANTS Forty-five community-dwelling people aged 65 and older who had baseline mobility limitations manifested by scores of 11 or lower on the Short Physical Performance Battery ( SPPB ) . INTERVENTIONS Subjects were r and omized into one of two 12-week exercise programs . The intervention group ( SCE ) ( n = 23 ) ascended and descended stairs , at a set pace , while wearing a weighted vest . The control group ( WALK ) ( n = 22 ) participated in a st and ardized walking program . MEASUREMENTS Primary and secondary outcomes included measures of muscle power and strength , submaximal aerobic capacity , and physical performance . RESULTS SCE produced 17 % improvement in double leg press peak power in comparison with WALK ( P = .013 ) and significant improvement in stair climbing power from baseline ( 12 % ) . Improvement in submaximal aerobic performance was equivalent for both groups . Although not statistically significant , effect size estimates suggest that SCE can potentially influence knee extension power and strength . Stair climb time was improved in both groups , whereas SCE produced significant improvements from baseline SPPB score in a subcohort of participants . CONCLUSIONS These findings suggest that SCE maybe a useful component of a home exercise program design ed to enhance lower extremity muscle power , aerobic capacity , and functional performance . Further investigation is needed involving larger sample sizes and direct comparisons with other forms of resistance training", "OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis", "PURPOSE Determine the independent and combined effects of progressive resistance muscle strength training ( PRMST ) and testosterone on strength , muscle mass , and function in hypogonadal elderly male recuperative care patients . METHODS Between 1999 and 2004 , 71 subjects ( mean age 78.2 + /- 6.4 yr , 86 % white ) were enrolled . After baseline one-repetition maximum ( 1RM ) strength testing and then r and omization to one of four treatment groups ( low-resistance ( 20 % of the 1RM ) exercises and weekly injections of either 100 mg of testosterone enanthate or placebo or high-intensity PRMST ( > or = 80 % 1RM ) and weekly injections ) , each subject received training and injections for 12 wk . RESULTS Ten subjects withdrew from the study before its completion . Based on intent-to-treat analyses , strength improved in all groups , but was greater with high-intensity PRMST compared with low-resistance exercise ( e.g. , leg press , ( mean + /- SE ) , 28 + /- 4 vs 13 + /- 4 % , P = 0.009 ) . Although testosterone led to significantly greater increases in midthigh cross-sectional muscle area compared with placebo ( 7.9 + /- 1.3 vs 2.4 + /- 1.4 % , P = 0.005 ) , it produced only a nonsignificant trend toward greater strength gains ( e.g. , leg press 25 + /- 4 vs 16 + /- 4 % , P = 0.144 ) . Change in aggregate functional performance score ( the sum of 4 functional performance test scores ) did not differ between the four intervention groups nor with high-intensity PRMST compared with low-resistance exercise ( 7 + /- 5 vs 15 + /- 5 % , P = 0.263 ) . There was not a significant interaction between exercise and testosterone for any outcome . CONCLUSION High-intensity PRMST is as safe and well tolerated as a similarly structured low-resistance exercise regimen for very frail elderly patients , but produces greater muscle strength improvements . The addition of testosterone leads to greater muscle size and a trend toward greater strength but did not produce a synergistic interaction with exercise . Neither intervention had a significant effect on functional performance", "BACKGROUND Older women with coronary artery disease ( CAD ) have reduced peak aerobic power ( Vo(2)peak ) , muscle strength , and quality of life ( QOL ) . Exercise interventions that can improve Vo(2)peak and muscle strength may also result in an improvement in QOL . This study compared the effect of aerobic training ( AT ) or combined aerobic and strength training ( COMT ) on Vo(2)peak , distance walked in 6 min , upper- and lower-extremity maximal strength , and QOL in 18 women ( age range , 60 to 80 years ) with documented CAD . METHODS After baseline testing , subjects were r and omly assigned to AT ( treadmill and cycle exercise , n = 9 ) or COMT ( treadmill and cycle exercise plus upper- and lower-extremity strength training , n = 9 ) , and each group exercised 3 d/wk for 8 weeks . RESULTS Both AT and COMT result ed in a similar increase in Vo(2)peak , distance walked in 6 min , lower-extremity strength , and emotional and global QOL . COMT improved upper-extremity strength , and physical and social QOL , which was unchanged after AT . CONCLUSIONS Older women with CAD should perform aerobic and strength training to attain optimal improvements in overall physical fitness and QOL", "This study assessed the effects of resistive training ( RT ) with or without chromium picolinate ( Cr-pic ) supplementation on the 24-h urinary excretions of myo-inositol , D-chiro-inositol , and pinitol , as well as clinical indices of kidney and liver functions . Thirty-two nondiabetic subjects , age 62 + /- 4 y , performed RT twice weekly for 12 wk and consumed either 924 ug Cr/d as Cr-pic ( n = 17 ) or a placebo ( n = 15 ) . Whole-body strength increased in all subjects by 20 % and urinary chromium excretion increased 47-fold in the Cr-pic group . Urinary myo-inositol , D-chiro-inositol , and pinitol were not changed with RT or influenced by Cr-pic . Serum indices of kidney and liver functions were within clinical ly normal ranges at baseline and the end of the study . These results suggest that RT did not influence the urinary excretions of inositols . High dose Cr-pic did not influence the urinary excretion of inositols and the selected indices of kidney and liver functions in conjunction with RT", "OBJECTIVES To compare the effectiveness of group resistance and agility-training programs in reducing fall risk in community-dwelling older women with low bone mass . DESIGN A r and omized , controlled , single-blind 25-week prospect i ve study with assessment s at baseline , midpoint , and trial completion . SETTING Community center . PARTICIPANTS Community-dwelling women aged 75 to 85 with low bone mass . INTERVENTION Participants were r and omly assigned to one of three groups : resistance training ( n=32 ) , agility training ( n=34 ) , and stretching ( sham ) exercises ( n=32 ) . The exercise classes for each study arm were held twice weekly . MEASUREMENTS The primary outcome measure was fall risk ( derived from weighted scores from tests of postural sway , reaction time , strength , proprioception , and vision ) , as measured using a Physiological Profile Assessment ( PPA ) . Secondary outcome measures were ankle dorsiflexion strength , foot reaction time , and Community Balance and Mobility Scale score . RESULTS Attendance at the exercise sessions for all three groups was excellent : resistance training ( 85.4 % ) , agility training ( 87.3 % ) , and stretching program ( 78.8 % ) . At the end of the trial , PPA fall-risk scores were reduced by 57.3 % and 47.5 % in the resistance and agility-training groups , respectively , but by only 20.2 % in the stretching group . In the resistance and agility groups , the reduction in fall risk was mediated primarily by improved postural stability , where sway was reduced by 30.6 % and 29.2 % , respectively . There were no significant differences between the groups for the secondary outcomes measures . Within the resistance-training group , reductions in sway were significantly associated with improved strength , as assessed using increased squat load used in the exercise sessions . CONCLUSION These findings support the implementation of community-based resistance and agility-training programs to reduce fall risk in older women with low bone mass . Such programs may have particular public health benefits because it has been shown that this group is at increased risk of falling and sustaining fall-related fractures", "BACKGROUND Depression in elderly people may be contributed to by the multiple losses of aging . Exercise has the potential to positively impact many of these losses simultaneously . We tested the hypothesis that progressive resistance training ( PRT ) would reduce depression while improving physiologic capacity , quality of life , morale , function and self-efficacy without adverse events in an older , significantly depressed population . METHODS We conducted a 10-week r and omized controlled trial of volunteers aged 60 and above with major or minor depression or dysthymia . Subjects were r and omized for 10 weeks to either a supervised PRT program three times a week or an attention-control group . RESULTS A total of 32 subjects aged 60 - 84 , mean age 71.3 + /- 1.2 yr , were r and omized and completed the study . No significant adverse events occurred . Median compliance was 95 % . PRT significantly reduced all depression measures ( Beck Depression Inventory in exercisers 21.3 + /- 1.8 to 9.8 + /- 2.4 versus controls 18.4 + /- 1.7 to 13.8 + /- 2 , p = .002 ; Hamilton Rating Scale of Depression in exercisers 12.3 + /- 0.9 to 5.3 + /- 1.3 versus controls 11.4 + /- 1.0 to 8.9 + /- 1.3 , p = .008 ) . Quality of life subscales of bodily pain ( p = .001 ) , vitality ( p = .002 ) , social functioning ( p = .008 ) , and role emotional ( p = .02 ) were all significantly improved by exercise compared to controls . Strength increased a mean of 33 % + /- 4 % in exercisers and decreased 2 % + /- 2 % in controls ( p depression scores ( r2 = .617 , p = .0002 ) . CONCLUSIONS PRT is an effective antidepressant in depressed elders , while also improving strength , morale , and quality of life", "OBJECTIVE To evaluate the influence of a twice-weekly progressive resistance training ( PRT ) program , without a concomitant weight loss diet , on abdominal fat and insulin sensitivity in older men with type 2 diabetes . RESEARCH DESIGN AND METHODS Nine older men ( aged 66.6 + /- 3.1 ) with type 2 diabetes participated in a 16-week PRT supervised program ( 50 - 80 % of the one repetition maximum ) , for all main muscle groups . Basal glycemia , HbA(1c ) , diet , habitual physical activity , body composition , and upper/lower maximal strength were measured . Insulin sensitivity was determined according to Bergman 's minimal model procedure and abdominal fat was obtained by computed tomography . The measurements were taken 4 weeks before training ( -4 ) , immediately before training ( 0 ) , and at 8-week intervals ( i.e. , weeks 8 and 16 ) during the 16-week training period . RESULTS No significant variation was observed in any of the above selected parameters during the 4-week control period . After PRT , both leg and arm maximal strength increased significantly by 17.1 and 18.2 % , respectively . Visceral and subcutaneous abdominal fat decreased significantly by 10.3 % ( from 249.5 + /- 97.9 to 225.6 + /- 96.6 cm(3 ) , P body mass . PRT significantly increased insulin sensitivity by 46.3 % ( from 2.0 + /- 1.2 to 2.8 + /- 1.6 . 10(4 ) . min(-1 ) . muU(-1 ) . ml(-1 ) , P fasting blood glucose ( from 146.6 + /- 28.3 to 135.0 + /- 29.3 mg/dl ) . Finally , a 15.5 % increase in energy intake ( from 2,287.1 + /- 354.7 to 2,619.0 + /- 472.1 kcal/day , P insulin sensitivity and fasting glycemia and decreases abdominal fat in older men with type 2 diabetes", "We evaluated the effect of a strength-training program on the ability of persons with essential tremor to exert steady forces with the index finger . Thirteen subjects with a diagnosis of essential tremor were assigned to three different groups : one group trained with heavy loads , one with light loads , and one did not perform any training . Subjects attempted to generate steady contractions during both postural and constant-force tasks . Steadiness was quantified by the root mean square amplitude of acceleration during postural tasks and the st and ard deviation and coefficient of variation of force during the constant-force tasks . Subjects who performed the training program with heavy loads experienced an increase in steadiness around the target force during the constant-force tasks . Subjects in the other two groups did not exhibit any changes . These findings suggest that strength training can decrease the magnitude of tremor . However , we did not observe any associated improvements in functional abilities", "PURPOSE This study evaluated the benefits of adding a psychological empowerment intervention ( PEI ) to traditional strength training ( TST ) on social cognitive variables in community-dwelling older adults . METHODS Thirty-eight participants were r and omly assigned to either a PEI or a TST intervention for 6 wk . Before r and om assignment and following training , participants completed measures of self-efficacy for upper and lower body strength as well as the desire to be able to lift specific amounts of weight . Both treatments involved two sessions per week of center-based training and one session per week of home-based training . The PEI condition also included a group-mediated intervention that was design ed to increase self-efficacy for physical strength and the desire for upper and lower body strength . RESULTS General linear models on difference scores revealed that the two groups experienced differential gains in the desire for upper body strength ( P = 0.023 , effect size ( ES ) = 0.79 ) and were marginally different in gains for upper body strength self-efficacy ( P = 0.065 , ES = 0.63 ) . On a four-point scale , the adjusted mean ( + /-SE ) differences for the PEI group on the desire for upper body strength was 0.71 ( + /-0.12 ) as compared to 0.27 ( + /-0.13 ) for the TST group , whereas the PEI group 's improvement in self-efficacy for upper body strength was 25.70 ( + /-3.02 ) as compared to 17.18 ( + /-3.19 ) for the TST group . CONCLUSIONS Empowerment-based exercise programs may be particularly motivating for older adults by creating a more meaningful physical activity experience for them", "We investigated if long-term resistance training would increase insulin-like growth factor-1 ( IGF-1 ) bioavailabilty at rest in older women ( 68+/-1 years ) with low bone mineral density . IGF-1 levels were significantly lower ( P insulin-like growth factor binding proteins -1 and -3 ( IGFBP-1 and IGFBP-3 ) significantly higher than an age-matched healthy normal group . Resistance training result ed in significant ( P repetition maximums across all exercises ( range 41 - 78 % ) . Resting IGF-1 levels were significantly ( P resistance training whereas no significant changes occurred in IGFBP-1 and IGFBP-3 levels . IGFBP-1/IGF-1 and IGFBP-3/IGF-1 ratios were significantly decreased ( approximately - 50 % ) as a result of resistance training ( P IGF-1 bioavailability was increased as a result of resistance training induced increases in IGF-1 levels in older women with low bone mineral density . These alterations in the IGF-1 system may be contributing to the significant strength gain observed with the resistance training in this population", "PURPOSE In patients with intermittent claudication ( IC ) a structured walking exercise program improves exercise performance . However , few studies have evaluated the effects of exercise training on functional status during daily activities . We hypothesized that a supervised exercise training program would improve functional status in patients with IC , with 24 weeks of training more beneficial than 12 weeks . A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status . METHODS Twenty-nine men with disabling IC were r and omized to 12 weeks of either supervised treadmill training ( 3 hr/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 hr/wk of resistive training of six muscle groups of each leg ) , or to a nonexercising control group . Functional status was assessed by question naires characterizing walking ability ( Walking Impairment Question naire , WIQ ) , habitual physical activity level ( Physical Activity Recall , PAR ) , and physical , social , and role functioning , well-being , and overall health ( Medical Outcomes Study SF-20 , MOS ) . Patients alos had their activity levels monitored with an activity monitor ( Vitalog ) . RESULTS After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk , the MOS physical functioning score by 24 percentage points , and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr ( all p WIQ scores . After 12 additional weeks of treadmill training improvements initially observed in the PAR , MOS , and Vitalog scores were maintained , and in addition the ability to walk distances ( WIQ ) improved by 31 percentage points , and the IC severity score had improved by 29 percentage points ( both p strength training patients improved their WIQ walking speed , stair climbing scores , and MOS well-being scores with no other changes in functional status . Subjects in the control group did not improve functional status by any measure . Twelve weeks of treadmill training after the strength training program maintained WIQ walking speed scores , and activity level defined by Vitalog improved . Twelve weeks of combined treadmill and strength training after the control period had no effect on functional status . CONCLUSIONS A supervised treadmill training program improved functional status during daily activities , with 24 weeks more effective than 12 . In addition , treadmill training alone was more effective in improving functional status in patients with IC than strength training or combinations of the training modalities", "Cardiac rehabilitation programs have not consistently been shown to improve the psychological well being of their patients . In our study of 38 cardiac patients ( 29 men and 9 women ) , a variety of quality -of-life parameters were assessed before and after they completed either 12 weeks of high-intensity strength training or flexibility training added to their outpatient cardiac rehabilitation aerobic exercise program . The strength-trained patients increased their self-efficacy scores for lifting ( 29 % vs 4 % , p Mood States dimensions : total mood disturbance ( 123 % vs 18 % , p depression/dejection ( 73 % vs 15 % , p fatigue/inertia ( 42 % vs 3 % p Medical Outcome Survey Short Form 36 role emotional health domain scores were significantly improved in the strength group when compared with the flexibility group ( 64 % vs 0 % , p role limitation scores improved in both groups . Increases in strength were associated with enhanced self efficacy and improved mood and well-being scores ( n = 34 , r = 0.30 to 0.53 , p High-intensity strength training added to a cardiac rehabilitation program of selected patients leads to improvements in quality -of-life parameters . These data , in conjunction with improvements in strength , strongly support the value of adding high-intensity strength training to cardiac rehabilitation programs", "Background and Purpose : Isotonic strength training can result in neuromuscular improvements evidence d in other forms of muscular effort , ie , isokinetic or isometric , especially in young subjects ; however , it is unclear if older muscle maintains this same adaptive ability . Additionally , it is not known if the benefits of resistance training can be augmented by creatine and protein supplementation in older men . Therefore , the purpose of this study was to assess changes in isokinetic parameters at varying speeds in men aged 48 to 72 years ( mean = 57 ± 2.1 ) following 16 weeks of isotonic resistance training and creatine and /or protein supplementation . Methods : Forty‐two male subjects were r and omly assigned to 1 of 4 training groups : ( 1 ) resistance training placebo ( n = 10 ) , ( 2 ) resistance trained creatine supplemented ( n = 10 ) , ( 3 ) resistance trained protein supplemented ( n = 11 ) , and ( 4 ) resistance trained creatine and protein supplemented ( n = 11 ) . The program consisted of progressive overload resistance training ( 3 d/wk ) and supplement consumption following the workout . Results : There were significant time effects ( P ≤ .05 ) for peak torque ( PT ) , time to PT , and average power for both the knee extensors and flexors at all velocities . However , no significant group or group by time interactions were noted , indicating that the supplementation protocol s had no added benefits . Conclusions : Men aged 48 to 72 years maintained their ability to improve isokinetic muscle function following isotonic training , however , supplementation did not enhance muscle adaptability ", "OBJECTIVE To evaluate the feasibility of a new functional tasks exercise program , design ed to improve functional performance of community-dwelling older women , by comparing it with a resistance exercise program . DESIGN A 12-week , r and omized , single-blind pilot study . SETTING A community leisure center . PARTICIPANTS Twenty-four community-dwelling , medically stable women ( mean age , 74.6+/-4.8 y ) were r and omized to the functional tasks exercises ( function group ) or the resistance exercises ( resistance group ) . Three participants withdrew from the study . INTERVENTIONS Exercises were given 3 times weekly for 12 weeks . The functional tasks exercise program aim ed to improve daily tasks in the domains first affected in older adults , whereas the resistance exercise program focused on strengthening the muscle groups that are important for functional performance . MAIN OUTCOME MEASURES Participant satisfaction with the exercises , Assessment of Daily Activity Performance ( ADAP ) , and , as a secondary outcome , muscle strength and power . RESULTS Exercise adherence was 81 % in the function group and 90 % in the resistance group . Participants reported greater satisfaction with the resistance exercises than with the functional exercises . The ADAP total score improved with time ( P = .001 ; mean change function group , 7.5 U ; 95 % confidence interval [ CI ] , 2.1 - 12.8 ; resistance group , 2.8 U , 95 % CI , -0.4 to 5.9 ) , as did isometric knee extensor strength ( P = .001 ; mean change function group , 6.4 % ; 95 % CI , -1.6 to 14.5 ; resistance group , 14.4 % ; 95 % CI , 6.4 - 22.2 ) . Testing for differences in outcomes between the 2 groups showed no statistically significant differences . CONCLUSIONS The functional tasks exercise program is feasible and shows promise of being more effective for functional performance than a resistance exercise program . A r and omized controlled trial with a larger sample size is needed to test the difference between the 2 programs", "Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density . However , the relationship between training dosage ( intensity , duration , frequency ) and the effect on bone density still is undergoing discussion . Furthermore , the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible . The aim of this investigation was to determine whether a clearly defined training of muscle strength , under defined safety aspects , performed only twice weekly , can counteract bone density loss in women with postmenopausal osteopenia . Data from 16 women in the training group ( age , 63.6 + /- 6.2 yr ) and 15 women in the control group ( age , 67.4 + /-9.7 yr ) , of comparable height and weight , were evaluated . Strength training was performed for 6 mo as continually adapted strength training , providing an intensity of about 70 % of each test person 's one repetition maximum . Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry . Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort . In addition , metabolic data were assessed . In the lumbar spine and femoral neck , the training group showed no significant changes , whereas the control group demonstrated a significant loss of bone mineral density , especially in the femoral neck ( P strength increase was highly significant in all exercised muscle groups , rising to about 70 % above the pretraining status ( P Heart rate and blood pressure data indicated a slight economization , metabolism was not significantly influenced . Based on these findings , we conclude that continually adapted strength training is an effective , safe , reproducible , and adaptable method of therapeutic strength training , following only two exercise sessions per week", "BACKGROUND Cardiovascular benefits of resistance training in cardiac patients have been suggested but not studied in a r and omized , controlled trial of circuit weight training ( CWT ) without an aerobic exercise component . The purpose of the current study was to examine the effects of 10 weeks of CWT on muscular strength , peak oxygen consumption ( peak VO2 ) , and myocardial oxygen dem and ( mVO2 ) in men after coronary artery bypass surgery . METHODS Twenty-six , post-coronary bypass male subjects ( mean 19 months after bypass ) , aged 60 + /- 8.5 years , were r and omly allocated to 10 weeks of CWT at 40 to 60 % of maximum voluntary contraction ( n = 12 ) or to a control group ( n = 14 ) . Muscular strength was assessed using a modified one repetition maximum technique . Peak VO2 was recorded during symptom-limited treadmill exercise . Rate pressure product , as an indirect measure of mVO2 , was measured during isometric , isodynamic , and dynamic exercise . RESULTS No ischemic symptoms nor electrocardiographic changes were recorded during testing or training . Strength increased by 18 % ( P peak VO2 . Rate pressure product during isometric and isodynamic exercise decreased from pre- to post-testing ( P Moderate intensity CWT is safe and can improve strength in selected low-risk patients after coronary artery bypass surgery . However , it does not significantly increase peak VO2 nor reduce mVO2 during isometric , isodynamic , and dynamic exercise", "Objective : To examine the effects of strength training on maximal force , cross‐sectional area ( CSA ) , and electromyographic ( EMG ) activity of muscles and serum hormone concentrations in elderly females with fibromyalgia ( FM ) . Methods : Twenty‐six patients with FM were r and omly assigned to a training ( FMT ; n = 13 ; mean age 60 years ) or a control ( FMC ; n = 13 ; 59 years ) group . FMT performed progressive strength training twice a week for 21 weeks . The measurements included maximal isometric and concentric leg extension forces , EMG activity of the vastus lateralis and medialis , CSA of the quadriceps femoris , and serum concentrations of testosterone ( T ) , free testosterone ( FT ) , growth hormone ( GH ) , insulin‐like growth factor‐1 ( IGF‐1 ) , dehydroepi and rosterone sulfate ( DHEAS ) , and cortisol . Subjectively perceived symptoms of FM were also assessed . Results : All patients were able to complete the training . In FMT strength training led to increases of 36 % ( p in maximal isometric and concentric forces , respectively . The CSA increased by 5 % ( p and the EMG activity in isometric action by 47 % ( p ) . Basal serum hormone concentrations remained unaltered during strength training . The subjective perceived symptoms showed a minor decreasing tendency ( ns ) . No statistically significant changes occurred in any of these parameters in FMC . Conclusion : Progressive strength training increases strength , CSA , and voluntary activation of the trained muscles in elderly women with FM , while the measured basal serum hormone concentrations remain unaltered . Strength training benefits the overall physical fitness of the patients without adverse effects or any exacerbation of symptoms and should be included in the rehabilitation programmes of elderly patients with FM", "OBJECTIVE To compare the effects of a hydrotherapy resistance exercise programme with a gym based resistance exercise programme on strength and function in the treatment of osteoarthritis ( OA ) . DESIGN Single blind , three arm , r and omised controlled trial . SUBJECTS 105 community living participants aged 50 years and over with clinical OA of the hip or knee . METHODS Participants were r and omised into one of three groups : hydrotherapy ( n = 35 ) , gym ( n = 35 ) , or control ( n = 35 ) . The two exercising groups had three exercise sessions a week for six weeks . At six weeks an independent physiotherapist unaware of the treatment allocation performed all outcome assessment s ( muscle strength dynamometry , six minute walk test , WOMAC OA Index , total drugs , SF-12 quality of life , Adelaide Activities Profile , and the Arthritis Self-Efficacy Scale ) . RESULTS In the gym group both left and right quadriceps significantly increased in strength compared with the control group , and right quadriceps strength was also significantly better than in the hydrotherapy group . The hydrotherapy group increased left quadriceps strength only at follow up , and this was significantly different from the control group . The hydrotherapy group was significantly different from the control group for distance walked and the physical component of the SF-12 . The gym group was significantly different from the control group for walk speed and self efficacy satisfaction . Compliance rates were similar for both exercise groups , with 84 % of hydrotherapy and 75 % of gym sessions attended . There were no differences in drug use between groups over the study period . CONCLUSION Functional gains were achieved with both exercise programmes compared with the control group", "Objective : To evaluate the additional effect of functional exercises on balance and lower extremity function among hostel-dwelling elderly people partaking in strength , training . Design : A r and omized two-group parallel controlled trial . Setting : A senior resident ’s hostel in Switzerl and . Participants : Thirty-two individuals r and omized to either strength or strength and functional exercise groups . Interventions : Both groups received machine-driven strength training for 45 min , twice weekly , for 12 weeks . The strength and functional exercises group received an additional 30 min of functional exercise training , once weekly . Main outcome measures : Tinetti test , balance tests and a physical performance test . Assessment s were performed before and after the intervention . Results : Improvements for the balance test depended on the type of training ( significant interaction effects [ F(1,20)= 6.7 ; P = 0.018 ] ) . This test improved from 11.3 ∓ 11.7 to 17 ∓ 11.2 ( P = 0.009 ) in the combined training group ( n = 12 ) and remained from 7.3 ∓ 9.5 to 6.9 ∓ 9.2 unchanged ( P = 0.821 ) in the strength training group ( n = 13 ) . A significant difference between groups following training was observed ( P = 0.031 ) . The Tinetti balance score and the chair st and test of the physical performance assessment improved from 14.3 ∓ 1.9 to 15.3 ∓ 1.1 ( P = 0.026 ) and 1.8 ∓ 1.2 to 2.8 ∓ 1.1 ( P = 0.012 ) respectively in the combined training group only . Conclusions : Our findings suggest that twice-weekly lower extremity strength training of 12 weeks ’ duration in hostel-dwelling elderly people only improves task-specific balance performance and lower extremity physical function when additional functional exercises are added", "BACKGROUND Systemic inflammation and protein-energy malnutrition may be associated with poor outcomes in kidney disease . METHODS We studied 26 adults ( age , 65 + /- 10 [ SD ] years ) with chronic kidney disease , not on dialysis therapy . Subjects were r and omly assigned to resistance training ( n = 14 ) or a control group ( n = 12 ) for 12 weeks , while counseled to consume a low-protein diet ( protein , approximately 0.6 g/kg/d ) . We determined whether resistance training reduces levels of inflammatory mediators ( serum C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) , in addition to previously reported improvements in nutritional and functional status in this same subject population . RESULTS Serum CRP levels were reduced in subjects undergoing resistance training ( -1.7 mg/L ) compared with controls ( 1.5 mg/L ; P = 0.05 ) . Similarly , IL-6 levels were reduced in the resistance-exercise group versus controls ( -4.2 versus 2.3 pg/mL ; P = 0.01 ) . Resistance training lead to skeletal muscle hypertrophy , shown by increases in type I ( 24 % + /- 31 % ) and type II ( 22 % + /- 41 % ) muscle fiber cross-sectional areas , compared with control subjects ( -14 % + /- 34 % and -13 % + /- 18 % , respectively ; P Muscle strength also improved with resistance training ( 28 % + /- 14 % ) compared with controls ( -13 % + /- 22 % ; P = 0.001 ) . CONCLUSION Resistance training reduced inflammation and improved nutritional status in individuals with moderate chronic kidney disease consuming a low-protein diet . These results need to be investigated further in larger cohorts of patients with varying stages of kidney disease to determine whether resistance training can improve disease outcomes long term", "Forty-seven elderly women ( 63 to 88 years of age , mean = 71 years ) were studied to determine the effect of a 25-week light resistance and aerobic exercise program upon arm and leg strength . Three groups were formed : nonexercising controls ( C , n = 12 ) , exercise ( EN , n = 18 ) and exercise with light weights on on the wrists and ankles ( EW , n = 17 ) . Exercise was performed for one hour , three times/week . Subjects were pretested and posttested for maximal isokinetic muscle strength ( angular velocity 60 degrees/sec ) for elbow flexion and extension , shoulder internal and external rotation , and knee flexion and extension . Dunn planned contrasts were used to compare C vs exercise groups combined ( EN + EW ) and EN vs EW . No significant differences were found among groups at baseline . EN + EW improved significantly ( p less than 0.05 ) more than C in elbow extension ( 17 % ) , shoulder internal rotation ( 14 % ) , shoulder external rotation ( 9 % ) , and knee flexion ( 20 % ) . No significant differences were found between EN and EW . These data indicate that elderly women can achieve substantial gains in the strength of arm and leg musculature as a result of regular light resistance and aerobic exercise , but that the use of light weights on the wrists and ankles for added resistance did not enhance this effect", "Krebs DE , Scarborough DM , McGibbon CA : Functional vs. strength training in disabled elderly out patients . Am J Phys Med Rehabil 2007;86:93–103 . Objective : To determine whether high-intensity functional training ( FT ) or strength training ( ST ) better enables impairment , disability , and functional gains among disabled community-dwelling elders . Design : R and omized , blinded , prospect i ve clinical trial in a large , tertiary care outpatient rehabilitation department . Fifteen elders ( 62–85 yrs old ) referred for physical therapy with one or more impairments , including lower-limb arthritis , participated in 6 wks of FT ( weekly outpatient and three to five times per week of home practice in rapid and correct execution of locomotor activities of daily living , including gait , stepping , and sit to st and ) or progressive resistive ST using elastic b and s with intensity , therapist contact , and home practice similar to those of FT . Results : Both groups significantly improved their combined lower-extremity strength ( hip abduction , ankle dorsiflexion , knee flexion , ankle plantarflexion , and knee extension ) ( P = 0.003 ) , but no statistical difference between the ST and FT group gains ( P = 0.203 ) was found . Subjects in both interventions improved their gait speed , but the FT group improved more than the ST group ( P = 0.001 ) . During chair rise , the FT group improved their maximum knee torque more than the ST group ( P = 0.033 ) , indicating that they employed a more controlled and efficient movement strategy . Conclusions : These data suggest that an intensive FT intervention results in strength improvements of comparable magnitude as those attained from ST and that FT also confers greater improvements in dynamic balance control and coordination while performing daily life tasks", "Aerobic exercise training is used for rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) , although it has little effect on muscle weakness and atrophy . Resistance training may be a useful addition to aerobic programs for these patients . The purpose of the present study was to investigate the effects of resistance training in addition to aerobic training on functional outcomes in patients with COPD . Seventeen COPD patients enrolled in an aerobic-based program that met twice a week were assigned to a 12-week control/aerobic [ CON : n=8 ; 63 ( 8) years ; mean ( SD ) ] or a resistance/aerobic group [ RES : n=9 ; 61 ( 7 ) years ] . RES trained an additional twice a week on 12 resistance machines , performing three sets of 8–12 repetitions at 32–64 % of their one-repetition maximum ( 1-RM ) lifts . RES ( P increased upper ( 36 % ) and lower ( 36 % ) body strength , as well as lean body mass ( 5 % ) , while CON showed little to no change . The 12-min walk distance increased ( P Measurements of three of the eight tasks of activities of daily living improved in RES ( P improved functional outcomes in COPD patients that were currently involved in an aerobic training program", "BACKGROUND Beneficial training outcomes have been reported in patients with chronic heart failure ( CHF ) following leg exercise training . However , data from more comprehensive training programs are limited . The aim of this study was to test the hypothesis that exercise training applying the concept of comprehensive local muscle training can improve aerobic and functional working capacity as well as quality of life in patients with CHF . METHODS Twenty-four men and women [ age 63+/-9 years ( mean+/-S.D. ) ] with stable , moderate chronic heart failure ( left ventricular ejection fraction 30+/-10 % ) , were investigated in a r and omized controlled study with a training group of 16 patients and a control group of 8 patients . The training was performed as an aerobic resistance training by activating all the main muscle groups , one at a time . The patients exercised for 1 h , three times per week for 8 weeks . RESULTS Patient groups did not differ at baseline . Peak oxygen uptake ( 8 % , P distance walked in a 6-min walking test ( 11 % , P health-related quality of life ( P plasma norepinephrine levels at rest ( 32 % , P peak oxygen uptake ( P quality of life scores ( P comprehensive physical training activating a minor muscle mass at a time markedly improves exercise capacity and quality of life and reduces catecholamine levels , it can be recommended for the rehabilitation of patients with CHF under supervision of a physical therapist", "BACKGROUND Age-related decline in muscle power may be an early indicator of balance deficits and fall risk , even in nonfrail adults . This study examined the dose-dependent effect of power training on balance performance in healthy older adults . METHODS One hundred twelve community-dwelling healthy older adults ( 69 + /- 6 years ) were r and omized to 8 - 12 weeks of power training at 20 % ( LOW ) , 50 % ( MED ) , or 80 % ( HIGH ) of maximal strength , or a nontraining control ( CON ) group . Participants trained twice weekly ( five exercises ; three sets of eight rapid concentric/slow eccentric repetitions ) using pneumatic resistance machines . Balance , muscle performance ( strength , power , endurance , contraction velocity ) , and body composition were measured . RESULTS Power training significantly improved balance performance ( p = .006 ) in participants who underwent power training compared to controls . Low intensity power training produced the greatest improvement in balance performance ( p = .048 ) . Average contraction velocity at low load ( 40 % one repetition maximum [ 1RM ] ) at baseline independently predicted improvement in balance following training ( r = -.29 , p = .004 ) . CONCLUSIONS Power training improves balance , particularly using a low load , high velocity regimen , in older adults with initial lower muscle power and slower contraction . Further studies are warranted to define the mechanisms underlying this adaptation , as well as the optimum power training intensity for a range of physiological and clinical outcomes in older adults with varying levels of health status and functional independence", "The purpose of this study was to determine whether a moderate to high intensity strengthening and aerobic exercise program can improve the strength , exercise capacity , gait and balance of deconditioned male nursing home residents . Ambulatory subjects who scored 30 or less on the modified Tinetti gait and balance assessment scale , who demonstrated less than 80 % of age-matched lower extremity strength on isokinetic muscle testing and who gave informed consent were enrolled . Subjects were r and omized to either an exercise ( n = 8) or a control ( n = 6 ) group . All participants underwent an exercise test to determine maximal oxygen uptake ( Vo2max ) and received quantitative gait and balance measurements . The subjects assigned to the exercise group then completed a 12-wk program of weight training for the lower extremities and stationary cycling . Both the exercise and control groups were then retested . Ten outcome variables were assessed : Tinetti mobility scores , Vo2max , isokinetic-tested lower extremity strength and endurance , stride length , gait velocity , stance time , gait duration , cadence and balance . The exercise group , after completion of the program , demonstrated significant improvements in Tinetti mobility scores ( P combined right and left quadricep muscle strength ( P right and left lower extremity muscular endurance ( P left stride length and gait velocity ( P control group revealed no changes of significance with the exception of improvement of the combined right and left hamstring muscle strength ( P < 0.05 ) . Nevertheless , for those outcome variables that had improved significantly in the exercise group , the changes amounted to only a 5 to 10 % increase over the baseline measurements . These findings showed that an appropriately design ed high intensity exercise program can result in significant although limited improvements for clinical mobility scores , strength , muscular endurance and certain gait parameters", "OBJECTIVE To compare 16 weeks of isometric versus dynamic resistance training versus a control on knee pain and functioning among patients with knee osteoarthritis ( OA ) . DESIGN R and omized clinical trial . SETTING Outpatient setting . PARTICIPANTS A total of 102 volunteer subjects with OA of the knee r and omized to isometric ( n=32 ) and dynamic ( n=35 ) resistance training groups or a control ( n=35 ) . INTERVENTIONS Strength exercises for the legs , 3 times weekly for 16 weeks . Dynamic group : exercises across a functional range of motion ; isometric : exercises at discrete joint angles . MAIN OUTCOME MEASURES The time to descend and ascend a flight of 27 stairs and to get down and up off of the floor . Knee pain was assessed immediately after each functional task . The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess perceived pain , stiffness , and functional ability . RESULTS In the isometric group , time to perform all 4 functional tasks decreased ( P time to descend and ascend stairs decreased by 13 % to 17 % . Both groups decreased knee pain while performing the functional tasks by 28 % to 58 % . Other measures of pain and functioning were significantly and favorably affected in the training groups . The improvements in the 2 training groups as a result of their respective therapies were not significantly different . The control group did not change over the duration of the study . CONCLUSION Dynamic or isometric resistance training improves functional ability and reduces knee joint pain of patients with knee OA", "PURPOSE And rogen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue , functional decline , increased body fatness , and loss of lean body tissue . These physical changes can negatively affect health-related quality of life . Resistance exercise may help to counter some of these side effects by reducing fatigue , elevating mood , building muscle mass , and reducing body fat . METHODS In a two-site study , 155 men with prostate cancer who were scheduled to receive and rogen deprivation therapy for at least 3 months after recruitment were r and omly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks ( 82 men ) or to a waiting list control group ( 73 men ) . The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported question naires after 12 weeks . Secondary outcomes were muscular fitness and body composition . RESULTS Men assigned to resistance exercise had less interference from fatigue on activities of daily living ( P = .002 ) and higher quality of life ( P = .001 ) than men in the control group . Men in the intervention group demonstrated higher levels of upper body ( P = .009 ) and lower body ( P muscular fitness than men in the control group . The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight , body mass index , waist circumference , or subcutaneous skinfolds . CONCLUSION Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving and rogen deprivation therapy . This form of exercise can be an important component of supportive care for these patients", "This study investigated the effects of heavy resistance training in elderly males with chronic obstructive pulmonary disease ( COPD ) . 18 Home-dwelling male patients ( age range : 65 - 80 years ) , with a mean forced expiratory volume in the first second ( FEV1 ) of 46 + /- 3.4 % of predicted value , were recruited . Baseline and post-training assessment s included : Cross-sectional area ( CSA ) of quadriceps assessed by MRI , isometric and isokinetic knee extension strength , isometric trunk strength , leg extension power , normal and maximal gait-speed on a 30 m track , stair climbing time , number of chair st and s in 30 s , lung function ( FEV1 ) and self-reported health . Subjects were r and omized to a resistance training group ( RE , n = 9 ) or a control group conducting breathing exercises ( CON , n = 9 ) . RE performed heavy progressive resistance training twice a week for 12 weeks . 6 RE and 7 CON completed the study . In RE the following improved ( P Quadriceps CSA : 4 % , isometric knee extension strength : 14 % , isokinetic knee extension strength at 60 degrees /s . : 18 % , leg extension power : 19 % , maximal gait speed : 14 % , stair climbing time : 17 % , isometric trunk flexion : 5 % and self-reported health . In CON no changes were found . In conclusion , 12 weeks of heavy resistance training twice a week result ed in significant improvements in muscle size , knee extension strength , leg extension power , functional performance and self-reported health in elderly male COPD patients", "The purpose of this study was to examine the effect of an intensity progressive strength training program on the performance of two tests related to fall risk : the Functional Reach Test ( FRT ) and the Timed Get‐Up‐ and ‐Go Test ( TUG ) . Twenty subjects were r and omly included in one experimental group ( age 73 ± 6 years old ) and one control group ( age 75 ± 5 years old ) . Subjects from the experimental group participated in a strength‐training program consisting of three sessions each week for a period of 14 consecutive weeks , from 50 % to 80 % of 1RM . A 2 ( group : experimental vs. control ) × 2 ( pre‐post : pre‐test vs. post‐test ) repeated measures ANOVA was carried out on subjects in TUG and FRT performance . Mean FRT results from the pre‐test were significantly lower than mean results from post‐test . The two main effects were qualified by a significant group × pre‐post interaction , F(1,18 ) = 39.23 , P markedly different performance profiles . Mean TUG results from the pre‐test were significantly lower than mean results from post‐test . The two main effects were qualified by a significant group × pre‐post interaction , F(1,18 ) = 50.74 , P markedly different performance profiles . Globally , the obtained results through our progressive strength‐training program showed important improvements in functional task performance and in preventing falls . Am . J. Hum . Biol . 17:746–751 , 2005 . © 2005 Wiley‐Liss ,", "OBJECTIVE To investigate the effects of a late-phase exercise program for patients who underwent total hip arthroplasty ( THA ) 4 to 12 months earlier . DESIGN A single-blind , r and omized controlled trial . SETTING Exercises were performed in subjects ' homes . Exercise instruction and measurements taken before and after the trial were performed in an outpatient research and treatment center . PARTICIPANTS Convenience sample of 34 adults 4 to 12 months post-THA r and omly allocated to experimental or control groups . Twenty-eight subjects completed the study . INTERVENTION An 8-week , hip-exercise intervention , during which the control group received basic isometric and active range of motion exercises ; the experimental group received strength and postural stability exercises . MAIN OUTCOME MEASURES Score on the 12-Item Hip Question naire ; fear of falling ; hip flexor , extensor , abductor , and knee extensor muscle torque ; and postural stability in single stance . RESULTS There was a statistically significant improvement in all measures of self-perceived function , muscle strength ( hip flexors , 24.4 % ; hip extensors , 47.8 % ; hip abductors , 41.2 % ; knee extensors , 23.4 % ) , and postural stability ( 36.8 % ) in the experimental group and no significant change in the control group . Neither group had statistically significant changes in fear of falling measures . CONCLUSIONS An exercise program emphasizing weight bearing and postural stability significantly improved muscle strength , postural stability , and self-perceived function in patients 4 to 12 months after THA", "PURPOSE To compare a weight training alone treatment ( WT ) to an innovative WT plus education treatment ( WT + ED ) about the use of strength-training gains when performing activities of daily living ( ADL ) with respect to their effects on ADL self-efficacy and performance . METHODS Twenty-three men and 41 women ( mean age = 74.4 + /- 3.7 yr ) were r and omly assigned to WT or WT + ED . Both groups performed 12 wk ( two sessions per week ) of WT targeting eight major muscle groups . WT + ED received behavioral training and associated written material s emphasizing the link between WT and ADL . WT received a placebo educational intervention . Baseline and posttest measures were collected for self-efficacy for performing eight lab-based ADL tasks and performance of the eight ADL tasks . A manipulation check compared participants ' knowledge of ADL that might be improved through WT . RESULTS The WT + ED treatment listed more ADL that could be improved with WT and had greater posttest self-efficacy for performing the ADL lab tasks than the WT treatment . Greater ADL self-efficacy did not translate into better ADL performance . CONCLUSIONS A targeted educational intervention can help older adults generalize the benefits and confidence obtained through WT to their performance of ADL . Further research is needed to determine the behavioral and psychosocial impact of enhanced ADL self-efficacy on older adults", "BACKGROUND Age-related declines in balance and muscle power are largely responsible for the changes in the various components of gait performance among elderly people . But these can often be remedied with strength training . People with cognitive impairment frequently demonstrate impaired gait , putting them at increased risks for falls and serious injury . OBJECTIVES This paper reports on the effects of a six-week pilot study of moderate intensity strength training on the gait of elderly individuals with dementia who attend a day-care center . METHODS Twenty-six adults ( 23 female , three male ) , age = 79.2 + /- 6.6 years , completed the study . Each subject completed a baseline assessment of lower extremity strength and gait . Gait was evaluated using free- and fast-gait speed over a 6-meter course , the Tinetti-Gait Assessment scale , the ' Timed-Up- and -Go ' , and the Gait Assessment Rating Scale ( GARS ) . The intervention consisted of moderate-intensity progressive resistance lower extremity exercise using Therab and , for two to three sessions per week over the six weeks . Post-intervention assessment of strength and gait was repeated at the completion of the sixth week . Multiple paired t-tests were calculated for each outcome measure . RESULTS The baseline assessment of gait suggests a high degree of frailty and risk for falls in the sample . Although post-intervention scores reflected improvement on all gait measures , the only statistically significant change observed was in fast-gait time . CONCLUSION A six-week resistance training program proved to be of insufficient duration , intensity or specificity to produce significant change in gait outcome measures , with the exception of fast speed gait", "BACKGROUND Resistance-training intervention studies have demonstrated meaningful health benefits in older adults ; however , most have used exercises performed at specific intensities on expensive equipment , which limit their widespread applicability . We tested whether two self-paced , less expensive exercise protocol s could be effective and safe for modifying neuromotor performance and functional capacity in community-dwelling adults 65 - 95 years of age . METHODS One hundred and thirty-one subjects were r and omized to a novel resistance training , walking , or control group . Subjects determined their level of resistance or walking intensity ( self-paced ) on a session-by-session basis . Muscle strength , balance , reaction time , stair climbing speed , and a timed pen pickup task were measured before and after the intervention period . Exercisers met three times per week for 10 months . RESULTS Significant improvements in t and em stance and single-legged stance with eyes open times and stair climbing speed were seen in both exercise groups . In addition , resistance trainers improved their muscle strength and ability to pick up an object from the floor and reduced the number of missteps taken during t and em walking , and walkers reduced t and em walking time . Controls showed no significant improvement in any variable . CONCLUSIONS The two self-paced exercise protocol s were effective at improving neuromotor performance and functional capacity in the study sample and show promise as a safe , effective , cost-efficient , acceptable exercise model for primary and secondary prevention in the general population of community-dwelling older adults", "OBJECTIVES Although deficits in skeletal muscle strength , gait , balance , and oxygen uptake are potentially reversible causes of frailty , the efficacy of exercise in reversing frailty in community-dwelling older adults has not been proven . The aim of this study was to determine the effects of intensive exercise training ( ET ) on measures of physical frailty in older community-dwelling men and women . DESIGN R and omized controlled trial . SETTING Medical school research center . PARTICIPANTS One hundred fifteen sedentary men and women ( mean age + /- st and ard deviation = 83 + /- 4 ) with mild to moderate physical frailty , as defined by two of the following three criteria : Modified Physical Performance Test ( modified PPT ) score between 18 and 32 , peak oxygen uptake ( VO2 peak ) between 10 and 18 mL/kg/min , and self-report of difficulty or assistance with one basic activity of daily living ( ADL ) , or two instrumental ADLs . INTERVENTION Participants were r and omly assigned to a control group that performed a 9-month low-intensity home exercise program ( control ) or an exercise-training program ( ET ) . The control intervention primarily consisted of flexibility exercises . ET began with 3 months of flexibility , light-resistance , and balance training . During the next 3 months , resistance training was added , and , during the next 3 months , endurance training was added . MEASUREMENTS Modified PPT score , VO2 peak , performance of ADLs as measured by the Older Americans Re sources and Services instrument , and the Functional Status Question naire ( FSQ ) . RESULTS ET result ed in significantly greater improvements than home exercise in three of the four primary outcome measures . Adjusted 95 % confidence bounds on the magnitude of improvement in the ET group compared with the control group were 1.0 to 5.2 points for the modified PPT score , 0.9 to 3.6 mL/kg/min for VO2 peak , and 1.6 to 4.9 points for the FSQ score . CONCLUSIONS Our results show that intensive ET can improve measures of physical function and pre clinical disability in older adults who have impairments in physical performance and oxygen uptake and are not taking hormone replacement therapy better than a low-intensity home exercise program", "The greater fluctuations in motor output that are often exhibited by old adults can be reduced with strength training . The purpose of the study was to determine the effect of strength and steadiness training by old adults on fluctuations in force and position during voluntary contractions with the quadriceps femoris muscle . Healthy old adults ( 65 - 80 yr ) completed 16 wk of heavy-load ( 80 % of maximum , n = 11 ) strength training , heavy-load steadiness training ( n = 6 ) , or no training ( n = 9 ) . Steadiness training required subjects to match the angular displacement about the knee joint to a constant-velocity template . The Heavy-Load group experienced a 5.5 % increase in muscle volume , a 25 % increase in maximal voluntary contraction force , and a 26 % increase in the one-repetition ( 1-RM ) load . The Heavy-Load Steady group experienced increases of 11.5 , 31 , and 36 % , respectively . The maximal electromyogram signal of quadriceps femoris increased by 51 % in the two training groups . The coefficient of variation ( CV ) for force during submaximal isometric contractions did not change with training for any group . Although both training groups also experienced a reduction in CV for force during anisometric contractions with a 50 % 1-RM load , the st and ard deviation of position did not change with time for any group . The Heavy-Load Steady group also experienced a reduction in CV for force during the training contractions performed with the 80 % 1-RM load . Thus strength training reduced the force fluctuations of the quadriceps femoris muscles during anisometric contractions but not during isometric contractions", "The effect of strength training for 14 weeks on patella tendon viscoelastic properties was investigated in a group of elderly individuals . Participants were assigned to training ( age [ mean + /- SD ] 73.6 + /- 3.4 years ; n = 7 ) or control ( age 66.4 + /- 1.7 years ; n = 7 ) groups . Training was performed three times per week and consisted of two series of 10 repetitions of leg-extension and leg-press exercises at 80 % of the 5-repetition maximum . Tendon elongation during an isometric knee-extension contraction-relaxation was measured using ultrasonography . Tendon stiffness was calculated from the gradient of the estimated force-elongation relationship and mechanical hysteresis was calculated as the area between loading-unloading curves . Knee-flexor coactivation , estimated from biceps femoris muscle electromyographic activity , was unaltered ( P > 0.05 ) after the training and control periods . No changes ( P > 0.05 ) were observed in stiffness or hysteresis after the control period . In contrast , tendon stiffness increased from 1376 + /- 811 to 2256 + /- 1476 N x mm(-1 ) ( P hysteresis decreased from 33 + /- 5 to 24 + /- 4 % ( P < 0.05 ) , after training . These training-induced adaptations have implication s for maximal muscle force , rate of force development , and metabolic cost of locomotion", "The purpose of the study was to compare the effects of three different types of group-based exercise programs ( resistance training , agility training and general stretching ) on back pain and health-related quality of life in older ( aged 75–85 years ) community-dwelling women with low bone mass ( i.e. , osteopenia or osteoporosis ) . The design was a 25-week r and omized controlled trial . Participating were 98 community-dwelling women with low bone mass between the ages of 75 to 85 years old . We assessed back pain and its related disability and health-related quality of life . All three types of group-based exercise programs significantly reduced back pain and its related disabilities , but only resistance and agility training significantly improved health-related quality of life in community-dwelling older women with low bone mass . Baseline physical activity level and class attendance were significant predictors of change in health-related quality of life . Change in back pain and its related disabilities after 25 weeks of exercise intervention was significantly correlated with change in health-related quality of life and changes in the domains of pain and physical function . Resistance and agility training significantly enhanced health-related quality of life and may have done so by increasing social interactions and support , enhancing self-efficacy of physical abilities and modifying the experience of back pain . These data provide valuable insight into the specifics of exercise prescription for older women with low bone mass . Future studies may wish to use individualized quality of life measures to further delineate the effects of different types of exercise on quality of life in older adults with low bone mass", "OBJECTIVE To assess the effects of 12 months ' dynamic strength training on muscle strength and bone mineral density ( BMD ) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis ( RA ) . METHODS Thirty-two subjects in the training group ( EG ) and 33 in the control group ( CG ) completed the study . EG carried out strength training 2 times a week with moderate loads of 50 - 70 % of repetition maximum . They were also encouraged to do recreational physical activities . CG performed recreational physical activities and range of motion exercises . Maximal strength of the knee extensors , trunk extensors and flexors , and grip strength were recorded with dynamometers . BMD was measured using dual x-ray absorptiometry . Modified Disease Activity Score , erythrocyte sedimentation rate , and pain were used for the estimation of disease activity , and Stanford Health Assessment Question naire to measure functional disability . RESULTS The 12 month resistance training in EG led to statistically significant mean increases of 22 - 35 % in all muscle groups examined . CG patients were also able to increase their strength to some degree ( 3 - 24 % ) , but at the end of the study strengths in CG were significantly lower than in EG . By the end of the study lumbar spine BMD had changed by + 0.19 % ( 4.24 ) in EG and by -1.14 % ( 4.36 ) in CG . The corresponding changes of femoral BMD were + 1.10 % ( 3.71 ) and -0.03 % ( 3.58 ) . The changes in BMD were minor and statistically not significant in both groups . However , femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids ( n = 15 , 3 subjects from EG and 12 from CG ) compared with changes in BMD among those not treated with systemic glucocorticoids ( n = 50 ) . CONCLUSION Minimally supervised strength training result ed in significant improvements in muscle strength without detrimental effects on disease activity . The detected annual changes in central BMD were minor and statistically insignificant in both groups . Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment", "This study compared the efficacy of 16 weeks of either resistance training , aerobic walking , or combined resistance training and aerobic walking on the performance of functional tasks among adults age 65 years and older with limited functional ability . One hundred thirty-one older adult individuals were r and omized into four groups : resistance training , aerobic walking , combined resistance and aerobic walking groups , or a nonexercise control group . Each of the exercise groups documented 70 % compliance with their respective exercise intervention , which included three weekly exercise sessions . At baseline , and 8 and 16 weeks following baseline , all participants completed six assessment s of their functional ability . Analysis of covariance indicated that all three exercise intervention groups significantly improved measures of functional ability , with the resistance group demonstrating the most consistent gains over the six measures . These findings indicate that older adults who are functionally limited can improve their functional ability through a variety of types of exercise", "Poor mobility has been associated with age-related deterioration in muscle strength . While previous work has examined the effects of improved strength on level walking , we have quantified the effects of a resistance-training program on obstructed gait tasks using biomechanical-dependent measures . Forty-five community-dwelling participants aged 62 years or older were r and omised to either a control ( n=16 ) or experimental group ( n=29 ) . The experimental subjects exercised for 24 weeks on a progressive resistance-training program design ed to improve lower body strength . Dynamic strength was assessed at weeks 0 and 24 as well as specific laboratory gait kinetics and kinematics during stepping over an obstacle and negotiation of a raised surface set at 10 , 20 and 30 % of each subject 's leg length . Significant strength improvements ( P strength gains in the experimental group were accompanied by significant increases in obstacle-crossing stride velocity ( range 5.5 - 15.5 % ) due to increases in stride length and decreases in stride duration for both gait tasks . Significant changes in the peak vertical and anterior-posterior ground reaction forces as well as in kinematic variables associated with a safe obstacle traverse such as vertical obstacle heel clearance , limb flexion at obstacle crossing , horizontal foot placement and vertical l and ing velocity result ed in an improved crossing strategy in the experimental subjects . These findings provide evidence of significant improvements in obstructed gait function of community-living older adults associated with a systematic resistance-training program", "It has been forwarded that strength training is the primary intervention for improving and maintaining functional independence of the elderly . The purpose of this study was to determine if a periodised strength-training program was superior to a fixed repetition protocol for enhancing strength in older adults . Previously untrained male and female participants ( 71.6+/-5.3 y ) were separated into three groups : fixed repetition ( FR : n= 18 ) , periodised ( PER : n= 21 ) and control ( C : n= 21 ) . FR and PER protocol s trained 2 days/week performing knee extensions , leg press , leg curl , biceps curl , triceps extension , lat pull downs , shoulder press and seated bench press . FR performed three sets of 9RM/exercise throughout the 18-week study . PER performed two sets of 15RM/exercise ( weeks 1 - 6 ) , three sets of 9RM/exercise ( weeks 7 - 12 ) and four sets of 6RM/exercise ( weeks 13 - 18 ) . Pre-post 1RM were collected for each exercise . The sum of 1RM for the eight exercises was considered indicative of total body strength and served as the dependent variable . An ANOVA with Bonferroni post hoc was utilised to analyse the data . FR ( p strength gains compared to C but were not different from each other . The results suggest that previously untrained older adults could expect similar strength gains from FR or PER strength-training protocol s of 18 weeks or less", "Chronic renal insufficiency , regardless of cause , generally progresses to end-stage renal disease ( 1 ) . Malnutrition and muscle wasting in chronic uremia often parallel the progression of renal failure ( 2 ) . They also contribute to excess morbidity and mortality in patients with renal disease ( 3 ) . Protein-restricted diets delay the progression of renal disease ( 4 , 5 ) and alleviate uremic symptoms ( 6 ) . Although nutritional status , as assessed by biochemical and anthropometric indicators , may be maintained during protein restriction ( 6 , 7 ) , studies have shown that deterioration of nutritional status is associated with low energy and protein intake in patients with chronic renal insufficiency ( 8) . Resistance training increases nitrogen retention ( 9 ) , protein synthesis ( 10 ) , and expression of insulin-like growth factor I in skeletal muscle ( 11 ) ; ameliorates losses of muscle mass and function ; and enhances quality of life ( 12 ) in both healthy and unwell persons . The anabolic potential of resistance training counteracts the catabolism of HIV infection ( 13 ) and myopathy secondary to corticosteroid use in cardiac transplantation ( 14 ) , the loss of lean tissue during energy restriction for obesity ( 15 ) , and the interleukin-mediated myopathy of chronic heart failure ( 16 ) . However , its utility as an adjunctive treatment off setting the catabolism of a low-protein diet in uremic patients is not known ( 17 ) . We conducted a r and omized , controlled trial to determine whether resistance training would preserve lean body mass , nutritional status , and muscle function through alterations in protein turnover ( synthesis and oxidation ) in patients with moderate chronic renal insufficiency who were consuming a low-protein diet to slow the progression of renal failure . Methods Study Design Patients older than 50 years of age with chronic renal insufficiency were r and omly assigned to a low-protein diet plus resistance training or a low-protein diet plus sham exercises ( referred to as low-protein diet alone ) . Patients were asked to follow a low-protein diet ( 0.6 g/kg of body weight per day ) for 2 to 8 weeks ( run-in period ) before r and omization . They continued the low-protein diet for an additional 12 weeks after r and omization ( intervention period ) ( Figure 1 ) . The Human Investigation Review Committee at Tufts University , Boston , Massachusetts , and collaborating hospitals approved the study , and written informed consent was obtained from all patients . Figure 1 . Flow of patients through the study . * The post office returned letters because addresses were incorrect or persons had relocated . No patients withdrew , experienced ineffective interventions , or were lost to follow-up . One patient in each group had incomplete postintervention measures because of health-related reasons . HNRCA = Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging . Study Sample Patients were recruited from the nephrology clinic at New Engl and Medical Center , Saint Elizabeth 's and Newton Wellesley Hospitals , and the Lahey Hitchcock Clinic , all in Boston , Massachusetts . Screening procedures took place at the Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging ( HNRCA ) at Tufts University . These procedures included sociodemographic and health history question naires ; physical examination ; electrocardiography ; blood hematology , chemistry , and urine analyses ; and a treadmill stress test . Eligibility criteria included serum creatinine concentrations between 133 and 442 mol/L ( 1.5 and 5.0 mg/dL ) and physician approval to follow a low-protein diet . A nephrologist confirmed renal diagnosis by review ing renal biochemistry results and clinical records . Exclusion criteria were myocardial infa rct ion ( within the past 6 months ) , any unstable chronic condition , dementia , alcoholism , dialysis or previous renal transplantation , current resistance training , recent involuntary weight change ( 2 kg ) , albumin level less than 30 g/L , proteinuria greater than 10 g/d , or abnormal stress test results at screening ( 18 ) . Reasons for early withdrawal from the study included loss of more than 25 % of initial body weight ; need for dialysis or transplantation ; development of any serious condition requiring hospitalization or precluding exercise ; and signs of malnutrition , such as a decrease in serum transferrin levels to less than 1.5 g/L or a 15 % decrease in hemoglobin or leukocyte count to below baseline levels . Diet Dietary intake of macronutrients and micronutrients and adherence to the low-protein diet were monitored twice per week during the run-in period and weekly during the intervention period by 3-day assisted dietary records ( including week and weekend days ) and regular meetings with the study dietitian , who was not blinded to group assignment . Dietary data were coded and analyzed by using Nutritionist-IV software ( N-Squared Computing , San Bruno , California ) . Patients collected one 24-hour urine specimen for every 3-day dietary record . Protein intake was also estimated by urea nitrogen levels ( 19 ) calculated from urine collection s and was used to assess adherence , which was defined as intake within 15 % of the prescribed low-protein intake ( 0.6 g/kg per day ) . Patients were counseled to reduce their habitual protein intake by eating food sources with less protein or by reducing portion sizes of higher-protein foods . Behavior modification strategies , including tips , recipes , food models , and self-monitoring tools for protein counts , were provided . These strategies were adapted from the Modification of Diet in Renal Disease Study ( 20 ) . Exercise Muscle strength was determined twice before r and omization and once after 12 weeks by measuring one repetition maximum ( 1 RM ) ( 21 ) using Keiser resistance training equipment ( Keiser Sports Health Equipment , Inc. , Fresno , California ) . One repetition maximum is the heaviest load that can be lifted once in good form through the full range of motion . Five machines ( chest and leg press , latissimus pull-down , knee extension , and knee flexion ) were used to include functionally large muscle groups . The better of the two baseline measurements of 1 RM was used in analyses and to set initial training loads for patients r and omly assigned to resistance training . All exercise sessions were performed at the HNRCA three times per week under the supervision of an exercise physiologist . Vital signs and body weight were recorded before each session . Patients who performed resistance training had monthly 1 RM testing on each machine . Workload during training was adjusted to reflect 80 % of the most recent 1 RM . In addition , patients ' workloads were progressively increased as appropriate according to the trainer 's objective perception of patients ' difficulty with workloads at each session . Patients performed three sets of eight repetitions on each machine per session , which lasted about 45 minutes ( 21 ) . Patients assigned to the low-protein diet alone performed five to eight sham exercises ( gentle movements while st and ing , sitting , and bending ) for the upper and lower body . These were design ed not to have a physiologic impact but to provide trainer contact time similar to that of the resistance training group . Study Measures All measures were taken before ( week 0 ) and 12 weeks after r and omization . Observers were blinded to study group assignment at all times , except during assessment s of postintervention muscle strength . Main Outcome Measures Total body potassium is the best single measure of body cell mass closely linked to functional status ( 22 ) , prognosis , and survival ( 23 ) . Body cell mass ( muscle and viscera ) comprises the metabolically active tissues where protein is targeted ( 24 ) . Potassium-40 represents approximately 0.0118 % of total body potassium . Loss of total body potassium occurs in patients following low-protein diets ( 25 ) and in patients with renal disease ( 26 ) , as well as in patients with many other wasting syndromes . Total body potassium was determined in the body composition laboratory at HNRCA , with a coefficient of variation of 5 % ( 24 ) . Regional body composition of the area involving the mid-thigh muscle was determined by computerized tomography of the nondominant thigh . A Siemens DR3 CT Scanner ( Somatom-Siemens , Erlangen , Germany ) was used to obtain an 8-mm scan at the midpoint between the inguinal crease and the proximal pole of the patella . Images were digitized and analyzed to the nearest 0.01 cm2 , as described elsewhere ( coefficient of variation , 0.5 % to 1.5 % ) ( 21 ) . Type I and type II muscle-fiber cross-sectional areas were determined from vastus lateralis muscle biopsies of the nondominant thigh , performed with a 5-mm Bergstrom needle ( 27 ) . Sections were stained with adenosine triphosphatase ( pH , 4.3 ) to visualize type I and type II fibers . A slide preparation was made for each biopsy specimen , and 50 to 150 fibers per patient were analyzed by light microscopy ( coefficient of variation , 3 % ) ( 11 , 27 ) . Anthropometry Body weights were measured to the nearest 0.1 kg on a Toledo Weight-Plate ( Bay State Scale & Systems , Inc. , Burlington , Massachusetts ) . Height was measured once to the nearest 0.25 cm , without shoes , by using a wall-mounted stadiometer . Body mass index was determined from body weight and height as kg/m2 . Biochemical Measures All measurements were collected in the fasting state in a blinded fashion at the nutrition evaluation laboratory at HNRCA ( coefficient of variation , 5 % to 10 % ) . Urea nitrogen and creatinine concentrations in serum and urine and levels of plasma insulin-like growth factor I were determined , as described elsewhere ( 25 , 27 ) . In addition , blood cell count ; hematocrit ; and levels of serum albumin , transferrin , and prealbumin were measured monthly to evaluate nutritional status . Glomerular Filtration Rate Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( Glofil , Cypros Pharmaceutical Corp. , Carlsbad , California ) , with a coefficient of", "OBJECTIVE Quadriceps weakness is a risk factor for incident knee osteoarthritis ( OA ) . We describe a r and omized controlled trial of effects of lower-extremity strength training on incidence and progression of knee OA . METHODS A total of 221 older adults ( mean age 69 years ) were stratified by sex , presence of radiographic knee OA , and severity of knee pain , and were r and omized to strength training ( ST ) or range-of-motion ( ROM ) exercises . Subjects exercised 3 times per week ( twice at a fitness facility , once at home ) for 12 weeks , followed by transition to home-based exercise after 12 months . Assessment s of isokinetic lower-extremity strength and highly st and ardized knee radiographs were obtained at baseline and 30 months . RESULTS Subjects in both groups lost lower-extremity strength over 30 months ; however , the rate of loss was slower with ST than with ROM . Compared with ROM , ST decreased the mean rate of joint space narrowing ( JSN ) in osteoarthritic knees by 26 % ( P = not significant ) . However , the difference between ST and ROM groups with respect to frequency of knee OA progression in JSN consensus ratings was marginally significant ( 18 % versus 28 % ; P = 0.094 ) . In knees that were radiographically normal at baseline , JSN > 0.50 mm was more common in ST than in ROM ( 34 % versus 19 % ; P = 0.038 ) . Incident JSN was unrelated to exercise adherence or changes in quadriceps strength or knee pain . CONCLUSION The ST group retained more strength and exhibited less frequent progressive JSN over 30 months than the ROM group . The increase in incident JSN > 0.50 mm in ST is unexplained and requires confirmation", "OBJECTIVE To determine the effect of a low load resistance exercise training program on muscle strength , functional outcome , and cardiovascular endurance . METHODS Forty-nine patients , 37 women and 12 men between the ages of 35 - 76 yrs ( mean 60.5 yrs ) , with definite rheumatoid arthritis ( RA ) functional class II and III ( mean disease duration of 10.5 yrs ) were r and omly assigned to exercise and control groups for a 12 wk resistive muscle training program . A circuit weight bearing form of training was incorporated using light loads with high repetitions . A video tape demonstrating the exercises was given to all exercising participants to enable them to continue the program at home at least 3 times per wk with a biweekly self-report evaluation . Baseline and post-intervention evaluations included joint activity , muscle strength , endurance , functional outcome , and self-report . Cardiovascular fitness measured by treadmill time , anaerobic threshold and peak oxygen consumption ( VO2 ) in this group were assessed at baseline and 12 wks . RESULTS A significant improvement at 12 wks was noted in the exercise group for self-reported joint count ( p = 0.02 ) , number of painful joints ( p = 0.004 ) , HAQ ( p = 0.012 ) , sit-to-st and time ( p = 0.02 ) , grip strength ( p = 0.05 ) knee extension 60 degrees ( p = 0.03 ) , Arthritis Impact Measurement Scales dexterity ( p = 0.02 ) , and time to anaerobic threshold ( p = 0.03 ) . Significant improvement in the exercise group compared to the control group was noted for self-reported joint count ( p = 0.02 ) , night time pain ( p = 0.05 ) , and sit-to-st and time ( p = 0.02 ) . Increase in treadmill time was not statistically significant nor was a change in peak oxygen consumption ( VO2 ) noted . Abnormalities on initial treadmill screening were detected in 2 of 49 asymptomatic patients . They were excluded from the study and subsequent workup revealed significant coronary artery disease . CONCLUSION Low load resistive muscle training increased functional capacity as reported by patients and is a clinical ly safe form of exercise in functional class II and III RA . Screening this population for dormant coronary artery disease is recommended", "Megestrol acetate ( MA ) ( Bristol-Myers Squibb Co. , Princeton , NJ ) increases weight gain in AIDS and cancer patients and in age-related cachexia ; however , the weight gain is predominately fat . We determined if adding resistance exercise and /or testosterone ( T ) replacement to MA administration would result in a more favorable body composition change than MA alone . Thirty older men ( aged 67.0 + /- 5.8 ) completed this 12-wk study . All subjects received MA and were r and omly assigned to one of the following groups : placebo ( P ) injections , resistance training ( RT ) and P ( RT + P ) , weekly injections of T ( 100 mg/wk ) or , RT and T ( RT + T ) . The mean increase in body weight for all groups combined was 3.8 kg ( P thigh muscle cross-sectional area ( P = 0.0006 ) . Thigh muscle cross-sectional area was significantly reduced from baseline by 5.20 [ 1.62 ] cm(2 ) ( P = 0.05 ) in P which was not prevented in T [ -4.44 ( 1.66 ) cm(2 ) from baseline ; P = 0.04 ] . RT prevented this decline [ + 0.61 ( 1.41 ) cm(2 ) from baseline ] . Muscle cross-sectional area increased 4.51 ( 1.69 ) cm(2 ) from baseline in RT + T ( P = 0.002 vs. P and P = 0.002 vs. T ) . Despite significant weight gain , MA appears to have an antianabolic effect on muscle size even when combined with T replacement . Resistance exercise attenuated this reduction in muscle mass and when combined with T had an anabolic effect on muscle mass", "This study was design ed to examine the psychological benefits of anaerobic exercise for older adults . Specifically , strength training was employed to examine the effects on mood and anxiety in a group of healthy but sedentary older women . 36 women ( mean age = 68.5 yr . ) were r and omly assigned to groups given high intensity or moderate intensity strength training or to a control group . Strength training was conducted three days a week for 12 weeks . After the training period , both high and moderate strength-training programs produced marked improvements in muscle strength and body composition compared to the control subjects . The average improvements in the high and moderate intensity strength-training groups for muscle strength were 40.5 and 35.5 % , respectively , and for percent body fat 1.52 and 2.50 % , respectively . As for psychological changes , both training groups significantly improved positive mood ( vigor ) , and the moderate intensity group significantly reduced trait anxiety compared to means of the control group . Also , both training groups showed some decrease in tension and state anxiety after the training period . These findings provide evidence for the effectiveness of anaerobic training to enhance perception of psychological well-being in older women . A moderate intensity rather than high intensity of training regimen may be more beneficial for sedentary older women to improve psychological health", "The study showed the effects of a 10-week resistance training program on flexibility of elderly women ( n = 11 ) between 62 and 78 years of age . The control group was composed of 8 women ( 62 to 73 years old ) who were physically inactive . Flexibility was evaluated through the sit- and -reach test , performed both before and after the training program . After an initial evaluation , individuals started a training program , which consisted of 8 exercises for the entire body , without the performance of any flexibility exercise . The training program result ed in significant increase ( p flexibility in elderly women ( 13 % ) . No significant differences were found in the control group . We conclude that weight training without performance stretching exercises does increase flexibility in elderly women", "OBJECTIVE To measure lumbar extensor strength in overweight ( OVW ) and nonoverweight ( NOVW ) elderly adults before and after resistance exercise training ( RX ) . DESIGN Descriptive , comparative study . SETTING University-based wellness center and research facility . PARTICIPANTS Eighty-four adults ( age range , 60 - 83 y ) were placed into 1 of 2 groups based on body mass index ( BMI ): control ( NOVW ; mean BMI , 22.5 kg/m(2 ) ) or OVW ( mean BMI , 29.2 kg/m(2 ) ) . Subjects were then r and omly assigned to either a resistance exercise ( RX ) or nonexercising group . INTERVENTION Six months of total body RX and isolated lumbar extension exercise . MAIN OUTCOME MEASURES Body composition , isometric lumbar extension strength , and 1-repetition maximum for each of the training exercises . RESULTS Upper-body strength increased by 18.3 % and 17.2 % for the NOVW-RX and OVW-RX groups , respectively . Lower-body strength increased by 12.7 % and 19.5 % for the NOVW-RX and OVW-RX groups , respectively . At baseline , the OVW participants had greater total lumbar extension strength ( 1067 Nm vs 714 Nm ) compared with the NOVW participants ( P total lumbar extension strength . After RX , lumbar extension strength increased by 58 % and 34 % for the NOVW-RX and OVW-RX groups , respectively ( P lumbar extension , upper- or lower-body strength were noted for the nontraining groups . CONCLUSIONS OVW subjects were found to have greater absolute and similar relative , upper-body , lower-body , and lumbar extension strength at baseline when compared with their NOVW counterparts . Also , isolated lumbar extension exercise was effective in improving lumbar extensor strength in OVW and NOVW persons", "Experimental evidence indicates that a lower synthesis rate of muscle contractile protein myosin heavy chain ( MHC ) occurs in age-related muscle wasting and weakness . To determine the molecular mechanism of this lower synthesis of MHC , we measured transcript levels of isoforms of MHC ( MHCI , MHCIIa , and MHCIIx ) in muscle biopsy sample s of 7 young ( 20 - 27 yr ) , 12 middle-aged ( 47 - 60 yr ) , and 14 older ( > 65 yr ) people . We further determined the effect of 3 mo of resistance exercise training ( exercise ) vs. nonintervention ( control ) on transcript levels of MHC isoforms on these subjects and the fractional synthesis rate ( FSR ) of MHC in 39 people aged 46 - 79 yr . MHCI mRNA levels did not significantly change with age , but MHCIIa decreased 38 % ( P MHCIIx decreased 84 % ( P FSR of MHC by 47 % ( P muscle protein by 56 % ( P Exercise training results in an increase ( 85 % ) in transcript levels of MHCI and a decrease in the transcript levels of MHCIIa and MHCIIx . In conclusion , an age-related lowering of the transcript levels of MHCIIa and MHCIIx is not reversed by exercise , whereas exercise results in a higher synthesis rate of MHC in association with an increase in MHCI isoform transcript levels", "Objective : To describe the independent and combined effects of oral nutrition supplementation and resistance training on health outcomes in nutritionally at risk older adults following lower limb fracture . Design : R and omized controlled trial with 12-week masked outcome assessment . Setting : Teaching hospital . Participants : One hundred nutritionally at risk older adults hospitalized following a fall-related lower limb fracture . Intervention : Commenced seven days after injury . Consisted of daily multinutrient energy-dense oral supplement ( 6.3 kJ/mL ) individually prescribed for six weeks ( n = 25 ) , tri-weekly resistance training for 12 weeks ( n = 25 ) , combined treatment ( n = 24 ) or attention control plus usual care and general nutrition and exercise advice ( n = 26 ) . Measurements : Weight change , quadriceps strength , gait speed , quality of life and health care utilization at completion of the 12-week intervention . Results : At 12 weeks , all groups lost weight : nutrition -6.2 % ( -8.4 , -4.0 ) ; resistance training -6.3 % ( -8.3 , -4.3 ) ; nutrition and resistance training -4.7 % ( -7.4 , -2.0 ) ; attention control -5.2 % ( -9.0 , -1.5 ) . Those receiving resistance training alone lost more weight than those receiving the combined treatment ( P = 0.029 ) . Significant weight loss was prevented if supplement was consumed for at least 35 days . Groups were no different at 12 weeks for any other outcome . Conclusion : Frail , undernourished older adults with a fall-related lower limb fracture experience clinical ly significant weight loss that is unable to be reversed with oral nutritional supplements . Those receiving a programme of resistance training without concurrent nutrition support are at increased risk of weight loss compared with those who receive a combined nutrition and resistance training intervention . In this high-risk patient group it is possible to prevent further decline in nutritional status using oral nutritional supplements if strategies are implemented to ensure prescription is adequate to meet energy requirements and levels of adherence are high", "The effects of 52 weeks resistance training at one of two exercise intensities on thigh muscle strength , fiber cross-sectional area ( CSA ) , and tissue composition were studied in healthy 65 - 79-year-old women . Subjects were assigned to either a control ( CO ) , high-intensity ( HI ) or low-intensity ( LO ) training group . Exercise regimens consisted of three sets of leg press , knee extension , and knee flexion exercises , 3 days/week , at either 80 % of one-repetition maximum ( 1-RM ) for seven repetitions ( HI ) or 40 % of 1-RM for 14 repetitions ( LO ) . Dynamic muscle strength was evaluated by 1-RM , thigh lean tissue mass ( LTM ) , fat mass , and bone mineral density ( BMD , g/cm2 ) by dual energy X-ray absorptiometry , and fiber CSA of vastus lateralis m. by histomorphometry . Muscle strength increased , on average ( + /- SEM ) , by 59.4 + /- 7.9 % and 41.5 + /- 7.9 % for HI and LO , respectively , compared to 1.3 + /- 4.8 % in CO ( P = 0.0001 ) . Type I fiber CSA increased over time ( P type II area ( HI , P = 0.06 ; LO , P = 0.11 ) . There was no significant effect of either exercise program on thigh tissue composition , except for BMD at the 1/3 site ( middle third of the femur ) , where LO and CO groups experienced a decline ( P thigh muscle strength , which were associated with fiber hypertrophy , although these did not translate into appreciable alterations in thigh tissue composition", "OBJECTIVE One of the factors that may promote deterioration in quality of life and body composition in elderly men is the relative decline in serum testosterone levels with aging . In this study , we assessed the effects of modest doses of testosterone and a home-based strengthening program on quality of life and body composition in elderly men with relative testosterone insufficiency . DESIGN Double-blind , placebo-controlled r and omized study ( testosterone ) , and additional r and omization to a resistance exercise program or no additional exercise for 12 weeks in men between ages of 65 and 85 years with relative testosterone insufficiency . METHODS Seventy sedentary , community dwelling men were r and omized to a 5 mg testoderm transdermal system applied daily vs placebo system , and additionally r and omized to a home-based resistance exercise program . Subjects were r and omized to Group 1 ( testosterone plus exercise ) , Group 2 ( testosterone plus no exercise ) , Group 3 ( placebo plus exercise ) , and Group 4 ( placebo plus no exercise ) . Endpoints included quality of life ( assessed by the short form-36 question naire ) and body composition ( measured by dual x-ray absorptiometry scan ) . RESULTS Serum testosterone increased by a mean of 10.0 + /- 1.9 , 6.6 + /- 1.6 , 0.52 + /- 0.6 , and 0.5 + /- 0.6 nmol/l in Groups 1 , 2 , 3 , and 4 respectively . There was a significant interaction of testosterone and exercise on quality of life in the domains of physical functioning ( P = 0.03 ) , role physical ( P = 0.01 ) , general health ( P = 0.049 ) , and social functioning ( P = 0.04 ) . There were no effects of testosterone or exercise on quality of life alone , nor in body composition parameters . CONCLUSIONS Modest testosterone supplementation to elderly men with relative testosterone insufficiency improved quality of life when accompanied by an exercise program . The combination of testosterone and exercise may be an important strategy in the elderly , though further studies are necessary to determine the long-term impact on body composition and function and for analysis of risk/benefit ratios as well", "This study determined the effects of endurance or resistance exercise training on maximal O2 consumption ( VO2max ) and the cardiovascular responses to exercise of 70- to 79-yr-old men and women . Healthy untrained subjects were r and omly assigned to a control group ( n = 12 ) or to an endurance ( n = 16 ) or resistance training group ( n = 19 ) . Training consisted of three sessions per week for 26 wk . Resistance training consisted of one set of 8 - 12 repetitions on 10 Nautilus machines . Endurance training consisted of 40 min at 50 - 70 % VO2max and at 75 - 85 % VO2max for the first and last 13 wk of training , respectively . The endurance training group increased its VO2max by 16 % during the first 13 wk of training and by a total of 22 % after 26 wk of training ; this group also increased its maximal O2 pulse , systolic blood pressure , and ventilation , and decreased its heart rate and perceived exertion during submaximal exercise . The resistance training group did not elicit significant changes in VO2max or in other maximal or submaximal cardiovascular responses despite eliciting 9 and 18 % increases in lower and upper body strength , respectively . Thus healthy men and women in their 70s can respond to prolonged endurance exercise training with adaptations similar to those of younger individuals . Resistance training in older individuals has no effect on cardiovascular responses to submaximal or maximal treadmill exercise", " Abstract The effects of a short-term strength training programme on resting lymphocyte subsets and stress hormone concentrations were analysed in 32 elderly sedentary subjects . Out of these 32 subjects , 8 women and 8 men [ mean age 70.1 ( SEM 1.0 ) years ] were r and omly assigned to a 8-week strength training programme which consisted of three sets of eight repetitions at 80 % of one repetition maximum , for leg press , bilateral leg extension and seated chest press , 3 days a week . The remaining 8 women and 8 men [ mean age 70.5 ( SEM 0.9 ) years ] served as controls . Absolute counts of lymphocyte subsets ( CD20 + , CD3 + , CD3+CD4 + , CD3+CD8 + , CD3−CD56+CD16 + ) were measured with a new technique combining fluorescent microspheres and flow cytometry . In the trained subjects , substantial increases in strength took place in one repetition maximum during the 8-week training period for leg press [ from means of 20.7 ( SEM 1.0 ) to 23.6 ( SEM 1.0 ) N · kg−1LBM ( lean body mass ) ] , chest press [ from means of 5.4 ( SEM 0.3 ) to 6.2 ( SEM 0.3 ) N · kg−1LBM ] and bilateral leg extension [ from means of 6.3 ( SEM 0.2 ) to 7.4 ( SEM 0.3 ) N · kg−1LBM ] movements . Baseline cortisol concentration ( P 0.01 ) , CD20 + cell count ( P 0.05 ) , CD3 + cell count ( P ) , and CD4 + cell count ( P strength training on resting adrenaline , noradrenaline and cortisol concentrations or distributions of lymphocyte subsets at rest was observed . The main finding of this study was to demonstrate that 8-week is too short a duration for a strength training programme to modify counts of lymphocyte subsets at rest in elderly sedentary adults", "Evidence indicates that leg weakness in older adults is associated with decreased control of balance . The gender-specific implication s of strength training on control of balance in older men and women remains unknown . This study examined the initial adaptations to 12 weeks of low-volume , single-set-to-failure strength training and its effect on quadriceps strength and control of multidirectional balance in previously untrained older men ( n = 11 ) and women ( n = 11 ) 59–83 years of age . Leg strength increased 23–30 % ( p effect on balance varied between genders . No significant changes were noted in the women , whereas 37 % ( p 0.014 ) more sway in the medial-lateral direction was noted in the men , with no change in the anterior-posterior direction . These results demonstrate that this training protocol may not be effective for improving balance and may lead to worsening of balance in older men", "PURPOSE Little is known concerning the effects of resistance-exercise training ( RT ) on older adult 's intra-abdominal adipose tissue ( IAAT ) . The purpose of this study was to determine the effects of RT on fat distribution in 12 women and 14 men , aged 61 - 77 yr . METHODS Computed tomography IAAT and abdominal subcutaneous adipose tissue ( SAT ) , densitometry-determined body composition , one-repetition maximum ( 1-RM ) , and isometric strength were measured before and after 25 wk of RT . Training consisted of two sets of 10 repetitions at 65 - 80 % of 1-RM , three times each week . RESULTS There were similar increases in strength for both the men and women . Women improved 22 % and 38 % in the isometric strength test and 1-RM test , respectively , whereas the men improved 21 % and 36 % , respectively . A significant increase in fat-free mass ( FFM ) was found for both men and women . However , there was a significant gender x time interaction , which indicated that men increased FFM more than women ( 2.8 kg vs 1.0 kg , respectively ) . Similar decreases in fat mass ( FM ) were found for the men ( 1.8 kg ) and women ( 1.7 kg ) . However , women lost a significant amount of IAAT ( 131 to 116 cm2 ) , whereas the men did not ( 143 to 152 cm2 ) . Similarly , women also lost a significant amount of SAT ( 254 to 239 cm2 ) , but men did not ( 165 to 165 cm2 ) . CONCLUSION Despite similar decreases in FM after a 25-wk RT program , older women lost significant amounts of IAAT and SAT , whereas the older men did not", "A r and omized , controlled , single-blinded 25-wk prospect i ve study was conducted to compare the effects of group-based resistance and agility training on bone , as measured by both dual-energy X-ray absorptiometry ( DXA ) and peripheral quantitative computed tomography ( pQCT ) , in older women with low bone mass . Ninety-eight community-dwelling women aged 75 - 85 yr were r and omized to one of three experimental groups : resistance training ( n = 32 ) , agility training ( n = 34 ) , or stretching ( sham exercise ) ( n = 32 ) . Total hip , femoral neck , and trochanteric bone mineral density ( BMD ) were measured by DXA . Peripheral QCT measurements were performed at the tibia and radius . The pQCT outcome measures at the shaft regions were cortical bone content , cortical bone cross-sectional area , cortical bone density , and density-weighted polar section modulus ( SSI ) . The pQCT outcome measures at the distal sites were total bone content , total bone cross-sectional area , and total bone density . At trial completion , the agility training group significantly increased cortical bone density by 0.5 + /- 0.2 % ( SE ) at the tibial shaft compared with a 0.4 + /- 0.3 % loss in the stretching group . The resistance training group significantly increased cortical bone density ( 1.4 + /- 0.6 % ) at the radial shaft compared , with a 0.4 + /- 0.5 % loss in the agility training group . No significant between-group differences were observed in the other bone outcome measures ( by DXA or pQCT ) . Future research is needed to determine the mechanism(s ) responsible for the observed adaptation of the cortical bone to mechanical loading", "OBJECTIVE Risk of falling increases as people age , and decreased leg strength and poor balance have been implicated as contributors . Our aims were to:1 ) assess the efficacy of a fall-prevention exercise program on balance and leg strength in women aged 65 to 89 years and 2 ) conduct a 1-year follow-up to determine the effect of exercise on fall rates . METHODS Forty women were classified by falling history and fear of falling and assigned to exercise and control groups using stratified r and omization . We used the Berg Balance Scale , Get-up and Go , Functional Reach , and Wall-Sit Tests to evaluate changes in balance and leg strength before and after a supervised 15-week exercise program ( 31-hr sessions/week ) . We conducted 1-year follow-up telephone interviews and compared the number of falls reported by exercise and control groups . The study used a 2 x 2 ( exercise/control by pretest/post-test ) factorial design with the testing times being a repeated factor , so we used analysis of variance ( ANOVA ) to evaluate differences between the 2 groups across testing times . Power analysis computed a priori with STPLAN software ( Version 4.2 ) showed that a sample size of 40 was necessary to determine statistical differences in balance and leg strength . RESULTS Exercise subjects showed significant improvement on 5 of 14 items ( 5.2 % , p Berg Balance Scale and on the total score ( 6.8 % , p Leg strength increased significantly ( p falls and exercise subjects no falls during the follow-up year , but this difference was not significant using Fischer 's exact test ( p=.106 ) . CONCLUSION The exercise program result ed in increased balance and leg strength , but did not result in a significant difference in falls during the follow-up period . Further research with a larger and possibly older sample is needed to more adequately investigate this question . Health care providers who work with older women should provide exercise programs in which balance and leg strength are emphasized", "OBJECTIVES To determine whether a functional-task exercise program and a resistance exercise program have different effects on the ability of community-living older people to perform daily tasks . DESIGN A r and omized , controlled , single-blind trial . SETTING Community leisure center in Utrecht , the Netherl and s. PARTICIPANTS Ninety-eight healthy women aged 70 and older were r and omly assigned to the functional-task exercise program ( function group , n=33 ) , a resistance exercise program ( resistance group , n=34 ) , or a control group ( n=31 ) . Participants attended exercise classes three times a week for 12 weeks . MEASUREMENTS Functional task performance ( Assessment of Daily Activity Performance ( ADAP ) ) , isometric knee extensor strength ( IKES ) , h and grip strength , isometric elbow flexor strength ( IEFS ) , and leg extension power were measured at baseline , at the end of training ( at 3 months ) , and 6 months after the end of training ( at 9 months ) . RESULTS The ADAP total score of the function group ( mean change 6.8 , 95 % confidence interval (CI)=5.2 - 8.4 ) increased significantly more than that of the resistance group ( 3.2 , 95 % CI=1.3 - 5.0 ; P=.007 ) or the control group ( 0.3 , 95 % CI=-1.3 - 1.9 ; P ADAP total score of the resistance group did not change significantly compared with that of the control group . In contrast , IKES and IEFS increased significantly in the resistance group ( 12.5 % , 95 % CI=3.8 - 21.3 and 8.6 % , 95 % CI=3.1 - 14.1 , respectively ) compared with the function group ( -2.1 % , 95 % CI=-5.4 - 1.3 ; P=.003 and 0.3 % , 95 % CI=-3.6 - 4.2 ; P=.03 , respectively ) and the control group ( -2.7 % , 95 % CI=-8.6 - 3.2 , P=.003 and 0.6 % , 95 % CI=-3.4 - 4.6 ; P=.04 , respectively ) . Six months after the end of training , the increase in ADAP scores was sustained in the function group ( P=.002 ) . CONCLUSION Functional-task exercises are more effective than resistance exercises at improving functional task performance in healthy elderly women and may have an important role in helping them maintain an independent lifestyle", "Sixty-two older adults ( 68.4+/-6 years ) were r and omized into a control group ( n=16 ) , low-intensity exercise group ( n=22 , LEX ; 50 % 1-repetition maximum ; 13 repetitions per exercise ) , or a high-intensity exercise group ( n=24 , HEX ; 80 % 1-repetition maximum ; eight repetitions per exercise ) group . Subjects trained for 24 weeks , performing 1 set for each of 13 exercises . Subjects performed a grade d exercise test ( GXT ) at baseline and after 24 weeks of strength training . Heart rate , systolic , and diastolic blood pressures were measured at rest , during the GXT and 1 , 3 , and 5-min post-GXT . Mean arterial pressure was also calculated . Post-training , time to peak systolic and diastolic blood pressures and heart rate was increased in the LEX and HEX groups by 22.9 % and 44.5 % , respectively ( p Diastolic blood pressure , heart rate , and mean arterial pressure during the GXT were significantly decreased ( p heart rate was lower in the HEX and LEX groups compared to control ( p peak cardiovascular responses , decreases the cardiovascular response to exertion , and improves recovery from maximal exertion", "Increased gait instability is common in older adults , even in the absence of overt disease . The goal of the present study was to quantitatively investigate the factors that contribute to gait instability and its potential reversibility in functionally impaired older adults . We studied 67 older men and women with functional impairment before and after they participated in a r and omized placebo-controlled , 6-mo multimodal exercise trial . We found that 1 ) gait instability is multifactorial ; 2 ) stride time variability is strongly associated with functional status and performance-based measures of function that have previously been shown to predict significant clinical outcomes such as morbidity and nursing home admission ; 3 ) neuropsychological status and health-related quality of life play important , independent roles in gait instability ; and 4 ) improvement in physiological capacity is associated with reduced gait instability . Although the etiology of gait instability in older persons with mild-moderate functional impairment is multifactorial , interventions design ed to reduce gait instability may be effective in bringing about a more consistent and more stable walking pattern", "BACKGROUND Although health-related benefits of fitness training in older men are well established , it is not clear yet which mode and intensity of a exercise program is most effective . This study addresses whether the combination of endurance ( ED ) and resistance training in older men have supplementary health-related benefits in addition to profits attained through endurance training alone . Additionally , effects of moderate- and low-intensity resistance training are compared . METHODS Men , 55 - 75 years of age , were r and omly assigned to a control group ( N = 13 ) or one of three exercise groups ( 20 weeks , two to three times per week ) : endurance plus moderate resistance ( MR ) training ( N = 22 ) , endurance plus low resistance ( LR ) training ( N = 22 ) and endurance training only ( N = 22 ) . Cardiovascular ( CV ) risk factors , muscular fitness and postural control were assessed before and after training . RESULTS All exercise groups revealed significant ( P resting heart rate , work capacity and recovery , waist girth , insulin response and knee-extensor strength with no differences among groups . Body composition , resting metabolic rate ( RMR ) , VO2peak and postural control did not change in exercise groups . CONCLUSION In older men , a fitness program consisting of 20 weeks endurance training combined with resistance training is equally effective as endurance training alone . Moderate vs. low resistance training added to endurance training yields similar health-related benefits", "Abstract The effects of 12 weeks of a low-intensity general conditioning programme on maximal instantaneous peak power ( W˙peak ) and maximal oxygen uptake ( V˙O2max ) were examined in 20 elderly women . After medical , familiarisation , and ethical procedures , the subjects were r and omly divided into either a training and or a control group . The training group [ n = 11 ; mean ( SD ) age 63.0 ( 3.1 ) years ] agreed to take part in a 12-week training programme at an exercise intensity kept under 60 % of the heart rate reserve for about 60 min , 3 times a week . The control group [ n = 9 ; mean ( SD ) age 63.5 ( 3.3 ) years ] did not perform any particular physical training . Before and after the training period , all participants underwent anthropometric measures and a maximal cycling test to exhaustion to measure their V˙O2max . In addition , W˙peak was determined 1 week later by the subjects performing a vertical jump from a squatting position on a force platform . Following training , neither the anthropometric characteristics nor the V˙O2max changed in either of the groups . In contrast , W˙peak increased significantly ( P an improved level of neuromuscular activation . Furthermore , it shows that although muscle power declines with age at a faster rate than does aerobic power , its sensitivity to training seems to be higher than that of the aerobic system", "BACKGROUND The performance of daily tasks , such as stair climbing or lifting an object , requires both muscle strength and power . Age-associated reductions in strength and power can affect an older adult 's ability to complete daily tasks such as stair climbing and lifting a child . METHODS The purpose s of this study were to determine whether power training was more efficacious than strength training for improving whole-body physical function in older adults and to examine the relationship between changes in anaerobic power and muscle strength and changes in physical function . Thirty-nine men and women ( mean age + /- SD = 72.5 + /- 6.3 years ) with below-average leg extensor power were r and omly assigned to control ( C , n = 15 ) , strength-training ( ST , n = 13 ) or power-training ( PT , n = 11 ) groups . The ST and PT groups met 3 days per week for 16 weeks ; the C group maintained usual activity and attended three lectures during the course of the study . Primary outcome measures included the Continuous Scale Physical Functional Performance test , maximal strength , and anaerobic power . RESULTS After baseline was controlled for , the Continuous Scale Physical Functional Performance test total score was significantly greater for the PT group than for the ST ( p = .033 ) and C ( p = .016 ) groups . Maximal strength was significantly greater for the ST group than for the C group ( p = .015 ) after the intervention . There was no significant difference between groups for peak anaerobic power . CONCLUSIONS Power training was more effective than strength training for improving physical function in community-dwelling older adults", "OBJECTIVE To evaluate the effectiveness of 2 rehabilitative approaches for improving paretic limb reaching by chronic stroke subjects . DESIGN Pre- and posttest reaching to targets ipsilateral , midline , and contralateral to the impaired side . SETTING Training in subjects ' homes ; testing in a laboratory setting . PARTICIPANTS Twelve poststroke volunteers were matched using the Motor Assessment Scale ( MAS ) and then were r and omly assigned to 1 of 2 training conditions . Subjects were subsequently categorized as at a high or low functional level , using the reaching pretest movement time scores . INTERVENTIONS Training ( trunk unrestrained ) using the paretic limb was 4 weeks ( 12 sessions ) . Task-related training ( TRT ) involved reaching to objects placed across the workspace . Progressive resistive exercise ( PRE ) involved whole-arm pulling against resistive therapeutic tubing in planes and distances similar to that in TRT . Main outcome measures Kinematic analysis of arm trajectory and trunk motion using the Peak Performance System , as well as scores on the MAS and the Rivermead Motor Assessment ( RMA ) . RESULTS For low-level groups , TRT result ed in increased substitutive trunk use at the target ipsilateral to the moving arm , and for midline and contralateral targets after PRE . Only low-level , TRT subjects straightened h and paths , which suggested better coordination of elbow-shoulder motion , and improved on the RMA . High-level subjects decreased trunk use at ipsilateral target after PRE , which was not observed after TRT . No significant differences between training conditions were found for other kinematic variables . CONCLUSIONS Training benefits appear to depend on initial level of functioning . Although compensatory trunk use was evident , low-level subjects seemed to benefit most from TRT . High-level subjects , whose kinematics showed fairly normal movement organization , demonstrated less compensatory movement after PRE", "OBJECTIVES To determine whether variation in resistance exercise volume affects muscle function and physical performance response in older adults . DESIGN A r and omized trial with subjects assigned to a single-set ( 1-SET ) or three-set ( 3-SET ) exercise group . SETTING An exercise facility at the University of Queensl and . PARTICIPANTS Twenty-eight community-dwelling men and women aged 65 to 78 . INTERVENTION Progressive resistance training consisting of seven exercises targeting the major muscle groups of the upper and lower body performed on exercise machines twice weekly for 20 weeks at eight-repetition maximum ( RM ) intensity . MEASUREMENTS Muscle function included isotonic muscle strength ( 1-RM ) of the seven exercises , isokinetic and isometric knee extensor strength , and muscle endurance for the chest press and leg press exercises . Physical performance included timed chair rise , usual and fast 6-m walk , 6-m backwards walk , 400-m walk , floor rise to st and ing , and stair climbing ability . In addition , body composition was determined using dual energy x-ray absorptiometry . RESULTS Isotonic muscle strength increased in both exercise groups for all seven exercises ( P seated row , triceps extension , and knee extension ( analysis of covariance ) . Similarly , muscle endurance gains were greater for the 3-SET than the 1-SET group ( P isokinetic and isometric knee extensor strength . Both groups improved ( P chair rise ( 1-SET , 10.1 % ; 3-SET , 13.6 % ) , 6-m backwards walk ( 1-SET , 14.3 % ; 3-SET , 14.8 % ) , 400-m walk ( 1-SET , 3.8 % ; 3-SET , 7.4 % ) , and stair climbing test ( 1-SET , 7.7 % ; 3-SET , 6.4 % ) , with the only difference between groups for the 400-m walk ( P body composition . CONCLUSION Resistance training consisting of only single-set exercises is sufficient to significantly enhance muscle function and physical performance , although muscle strength and endurance gains are greater with higher-volume work . These findings have application in design ing time-efficient exercise regimens to enhance neuromuscular function in older adults", "Knee extension strength , walking speed , quadriceps muscle mass and composition of the muscle compartment were studied in 66 to 85-year-old female athletes and controls . Maximal voluntary knee extension force , force/body mass , extension torque , torque/body mass and walking speed were higher for the athletes than the controls . A muscle index indicating intramuscular fat and connective tissue measured using ultrasonography was lower for the athletes than the controls . There were no differences between the study groups in knee extension force related either to cross-sectional area ( CSA ) or lean tissue area ( CSAL ) of the quadriceps . Within the subgroups , there was no significant correlation between knee extension torque and CSA or CSAL of the same muscle . In the athletes high knee extension torque/body mass was related to a low muscle index and high walking speed to a low relative proportion of fat in the muscle . The muscle index was lower the more kilometers trained during the preceding year . In the controls high knee extension torque/body mass and high walking speed were related to a low relative proportion of fat . Knee extension torque and walking speed were higher the more kilometers walked during the preceding year . The results indicate that elderly female athletes have superior muscle performance compared to their age-peers . Performance in a maximal isometric strength test in elderly women is not clearly related to muscle mass . However , to some extent it is related to the composition of the same muscle , especially the degree to which fat is infiltrated into the muscle", "Objective : To determine whether systematic progressive high-intensity quadriceps training increases leg extensor power and reduces disability in patients rehabilitating after proximal femoral fracture . Design : Open parallel group r and omized controlled trial comparing the addition of six weeks quadriceps training ( 40 patients ) with st and ard physiotherapy alone ( 40 patients ) . The training group exercised twice weekly , with six sets of 12 repetitions of knee extension ( both legs ) , progressing up to 80 % of their one-repetition maximum . Setting : Orthogeriatric unit , and community follow-up . Subjects : Eighty patients rehabilitating after proximal femoral fracture . Main outcome measures : Measurements of leg extensor power ( Nottingham Power Rig ) , functional mobility ( elderly mobility score ) , disability ( Barthel Index ) and quality of life ( Nottingham Health Profile ) were made at baseline , after six weeks ( at the end of the intervention ) and at 16 weeks . Results : Leg extensor power increased significantly in the quadriceps training group ( fractured leg mean improvement at six weeks 157 % ( st and ard error 16 ) , nonfractured leg 80 % ( 12 ) ) compared with the control group ( 63 % ( 11 ) and 26 % ( 8) respectively , unpaired Student 's t-test p = 0.007 and p = 0.01 for between-group comparisons ) . Significant benefits were maintained at 16 weeks . Quadriceps training result ed in a greater increase in elderly mobility scale score compared with st and ard rehabilitation ( between-group difference of 2.5 ( 95 % CI 1.1,3.8 ) at week 6 and 1.9 ( 0.4,3.4 ) at week 16 ) . Barthel score increased significantly from week 0 to 6 in the quadriceps training group compared with controls ( Mann – Whitney U-test p = 0.05 ) . Patients in the quadriceps training group scored significantly better in the energy subscore of the Nottingham Health Profile at the end of follow-up ( Mann – Whitney U-test p = 0.0185 ) . Conclusions : Progressive high-intensity quadriceps training in elderly proximal femoral fracture patients increased leg extensor power and reduced disability . This was accompanied by an increase in energy as measured by the Nottingham Health Profile . This intervention may provide a simple practical way of improving outcome in these patients", "OBJECTIVE To determine the effects of resistance training on muscular strength , body composition ( percent fat and lean tissue mass ) , and program adherence in active women over 60 years of age . DESIGN This study was design ed as a stratified , r and omized , non-blinded trial . Subjects were stratified into rank-ordered pairs by level of physical activity according to the Blair Seven-Day Recall , then r and omly assigned into either a weight-training ( WT , n = 18 ) or control ( CON , n = 18 ) group . PARTICIPANTS AND SETTING Thirty-six women over the age of 60 ( 67.1 + /- 1.5 , chi + /- SE ) were recruited from the San Diego community . All subjects had to be engaging in some form of aerobic exercise at least 3 days each week for a minimum of 6 months . MEASUREMENTS AND INTERVENTION : Subjects engaged in isotonic training 3 days/week on Polaris machines at a target intensity of 80 % of the 1 repetition maximum ( 1 RM ) for three sets of seven exercises selected to train major muscle groups of the trunk and upper and lower body . The 1 RM was re-tested every 6 weeks in WT and the workload adjusted to maintain target intensity . The 1 RM was tested at 0 , 12 , and 24 weeks in CON . Body fatness and lean tissue mass , excluding skeletal mass , were assessed at 0 and 24 weeks by dual energy radiography using a total body scan . RESULTS Increases in muscle strength of the weight trainers were significant for all seven exercises ( 5%-65 % ) , with the greatest gains in the shoulder and trunk muscles . Percent body fat of weight trainers decreased significantly ( from 38.8 % to 37.9 % , P lean tissue mass increased by 1.5 kg ( P body composition were observed in control subjects . Overall program adherence was 83 % ( 15 weight trainers and 15 control women completed the study ) . Monthly attendance averaged 86.8 + /- 3.3 % , with no incidence of injury during the training sessions . CONCLUSIONS These data indicate that heavy-resistance weight training is safe and enjoyable for older women and that meaningful gains in muscular strength and body composition can be made even in women who are already highly active", "Patients with heart failure ( HF ) often have profound activity limitations and diminished quality of life ( QOL ) due to symptoms of dyspnea and fatigue . Although recent studies demonstrate positive physiologic and psychological benefits of low to moderate intensity , supervised , aerobic exercise training performed 3 to 5 days/ week for 20 to 40 minutes ' duration , in a monitored setting , the efficacy of a home-based exercise program combining endurance and resistance exercise on symptoms and QOL , are unknown . This r and omized controlled study examined the efficacy , safety , and adherence rates of a 3-month home-based combined walking and resistance exercise program on symptoms and QOL in 40 women and men aged 30 to 76 years with New York Heart Association class II to III HF . Baseline and 3-month evaluations consisted of a chronic HF question naire to assess symptoms and QOL and exercise capacity by symptom-limited treadmill exercise test with respiratory gas analysis . The exercise intervention improved fatigue ( p = 0.02 ) , emotional function ( p = 0.01 ) , and mastery ( p = 0.04 ) . Overall exercise adherence was excellent ( 90 % ) and there were no reported adverse events . A moderate intensity home-based combined walking and resistance program for patients with class II to III HF is safe and effective in reducing symptoms and improving QOL", "PURPOSE We present final outcomes from the multiple-component Fit and Strong ! intervention for older adults with lower extremity osteoarthritis . DESIGN AND METHODS A r and omized controlled trial compared the effects of this exercise and behavior-change program followed by home-based reinforcement ( n=115 ) with a wait list control ( n=100 ) at 2 , 6 , and 12 months . Fit and Strong ! combined flexibility , aerobic walking , and resistance training with education and group problem solving to enhance self-efficacy for exercise and maintenance of physical activity . All participants developed individualized plans for long-term maintenance . RESULTS Relative to controls , treatment participants experienced statistically significant improvements in self-efficacy for exercise ( p=.001 ) , minutes of exercise per week ( p=.000 ) , and lower extremity stiffness ( p=.018 ) at 2 months . These benefits were maintained at 6 months and were accompanied by increased self-efficacy for adherence to exercise over time ( p=.001 ) , reduced pain ( p=.040 ) , and a marginally significant increase in self-efficacy for arthritis pain management ( p=.052 ) . Despite a substantially smaller sample size at 12 months , significant treatment-group effects were maintained on self-efficacy for exercise ( p=.006 ) and minutes of exercise per week ( p=.001 ) , accompanied by marginally significant reductions in lower extremity stiffness ( p=.056 ) and pain ( p=.066 ) . No adverse health effects were seen . Effect sizes for self-efficacy for exercise and for maintenance of physical activity were 0.798 and 0.713 , and 0.905 and 0.669 , respectively , in the treatment group at 6 and 12 months . IMPLICATION S This consistent pattern of benefits indicates that this low-cost intervention is efficacious for older adults with lower extremity osteoarthritis", "The authors previously found that creatine ( Cr ) combined with 12 weeks of resistance training enhanced muscle strength and endurance and lean tissue mass ( LTM ) in older men . Their purpose in this study was to assess these variables with cessation of Cr combined with 12 weeks of reduced training ( 33 % lower volume ) in a subgroup of these men ( n = 8 , 73 years old ) compared with 5 men ( 69 years old ) who did not receive Cr . Strength ( 1-repetition maximum [ 1-RM ] ) , endurance ( maximum number of repetitions over 3 sets at 70 - 80 % 1-RM ) , and LTM ( dual-energy X-ray absorptiometry ) were assessed before and after 12 weeks of Cr cessation combined with reduced-volume training . No changes in strength or LTM occurred . Muscle endurance was significantly reduced ( 7 - 21 % ; p Cr had no effect on the rate of strength , endurance , and loss of lean tissue mass with 12 weeks of reduced-volume training", "OBJECTIVE To examine the effect of 6 months of high- or low-intensity resistance exercise on aerobic capacity and treadmill time to exhaustion in adults aged 60 to 83 years . METHODS Sixty-two men and women completed the study protocol . Subjects were matched for strength and r and omly assigned to a control ( n = 16 ) , low-intensity exercise ( LEX , n = 24 ) , or high-intensity exercise ( HEX , n = 22 ) group . Subjects trained at either 50 % of their one repetition maximum ( 1-RM ) for 13 repetitions ( LEX ) or 80 % of 1-RM for 8 repetitions ( HEX ) 3 times per week for 24 weeks . One set each of 12 exercises was performed . Strength was measured for the leg press , chest press , leg curl , leg extension , overhead press , biceps curl , seated row , and triceps dip . Muscular endurance was measured for the leg press and chest press . Aerobic capacity ( peak oxygen consumption [ VO(2)peak ] ) was measured during an incremental treadmill test ( Naughton ) . Treadmill time to exhaustion was measured as the time to exhaustion during the incremental exercise test . RESULTS The 1-RM significantly increased ( P Aerobic capacity increased ( P Treadmill time increased ( P aerobic capacity and treadmill time to exhaustion can be obtained in older adults as a consequence of either high- or low-intensity resistance exercise . These findings suggest that increased strength , as a consequence of resistance exercise training , may allow older adults to reach and /or improve their aerobic capacity", "The quadriceps strength of a group of residents homes for the elderly ( mean age 83 years ) was assessed in a r and omized controlled trial of seated group exercise versus group reminiscence therapy . Fifty-five of 65 volunteers completed the 6-month study , with 4 dropouts from the exercise group , and 6 dropouts from the reminiscence group . There were no adverse effects . Average of attendance at the exercise sessions was 72 % ( range , 18 % to 98 % ) and 62 % ( range , 29 % to 100 % ) at the reminiscence sessions . The reminiscence sessions comprised group interaction and discussion prompted by the use of reminiscence aids . By the end of the study , the change observed in the exercise group was significantly different from the reminiscence group in terms of quadriceps strength ( p ability to climb up steps , but neither cognitive function ( Mini-Mental State Examination ) nor reaction time altered significantly ", "BACKGROUND Age-related loss in physiologic capacities contributes to the decline in physical function in the elderly population . Despite the beneficial effects of exercise interventions on maximal physiologic capacity measures , the functional benefits have not been shown in independently living older adults . The objective of this study was to evaluate exercise in independent older adults for significant and meaningful improvements in physical function , not detected by commonly used measures of physical function . METHODS In a r and omized controlled study , 49 independently living men and women were assigned to either a nonexercise control group ( Control ; n = 26 ) or an exercise training group ( Exercise ; n = 23 ) . Participants ( age = 76+/-4 ) in good general health were recruited from retirement communities or apartments . The combined endurance and strength training was performed at 75 % to 80 % intensity ; the groups met 3 times/week for 6 months of supervised sessions . Outcome measures included physical capacity , health status , and physical function using a newly developed performance test -- the Continuous Scale-Physical Functional Performance test ( CS-PFP ) . RESULTS Compared to the Control group , the Exercise group showed significant increases in maximal oxygen consumption ( 11 % ) and muscle strength ( 33 % ) . No significant differences were found between groups for changes in the Sickness Impact Profile , SF-36 scales , or the 6-minute walk . However , the CS-PFP score improved significantly in the Exercise group ( 14 % , effect size 0.80 ) . CONCLUSIONS Independent older adults gain meaningful functional benefits from several months of exercise training . The public health importance of physical activity may relate not just to its role in preventing decline , but also to its role in enhancing physical function", "Thirty-nine healthy women ( 59.5 + /- 0.9 yr ) were r and omized to either a control group ( CON ) or a progressive resistance training group ( PRT ) that trained twice weekly for 12 months . PRT trained at 80 % or more ( average of 84 % ) of their most recent one repetition maximum ( 1RM ) on the lateral pull-down ( LPD ) , knee extensor ( KE ) , and double leg press ( DLP ) apparatus . One RM was measured for each exercise once monthly in PRT and at baseline , mid study , and end of study in CON . One RM significantly increased in PRT for all muscle groups trained compared to CON ( P KE , DLP , and LPD in PRT and 12.7 % + /- 8 % , 3.7 % + /- 3 % , and 18.4 % + /- 4 % , respectively , in CON were observed . Approximately 50 % of the gains in KE and LPD and 40 % in the DLP were seen in the first 3 months of the study . In all three exercises , strength gains in PRT continued over the entire 12-month period . These data indicate that high-intensity strength training results in substantial , continual increases in strength in postmenopausal women for at least 12 months , with the greatest gains seen in the first 3 months of training", "In order to examine the relative contribution of neural- and muscle-based adaptation to strength training , we studied early ( 2 weeks ) and later ( 12 weeks ) effects of strength training on muscle size and strength and type I single-fiber size and contractility in 14 elderly women ( aged 68 - 79 years ) and seven young controls . Older subjects were r and omized to training ( n = 7 ) or control ( n = 7 ) groups . Strength did not change , but whole muscle size increased significantly after 2 weeks . After 12 weeks , strength , whole muscle size , and specific force all increased . No changes occurred in the control group . In single fibers , no changes in size and contractility were noted after 2 weeks , but specific force was higher in the training group after 12 weeks . Early adaptations to strength training in elderly women can not be attributed to changes at the cellular level and therefore occur primarily in the central nervous system . Later , cellular adaptations in specific force track closely whole muscle changes", "OBJECTIVE Reduced muscle mass and strength are characteristic findings of growth hormone deficiency ( GHD ) and aging . We evaluated measures of muscle strength , muscle fiber type , and cross sectional area in response to treatment with recombinant human growth hormone ( rhGH ) with or without a structured resistance exercise program in frail older subjects . DESIGN Placebo-controlled , r and omized , double blind trial . SETTING Outpatient clinical research center at an urban university-affiliated teaching hospital . PARTICIPANTS Thirty-one consenting older subjects ( mean age 71.3 + /- 4.5 years ) recruited as a subset of a larger project evaluating rhGH and exercise in older people , who underwent 62 quadricep-muscle biopsies . INTERVENTION R and om assignment to a 6-month course of one of four protocol s : rhGH administered subcutaneously daily at bedtime , rhGH and a structured resistance exercise program , structured resistance exercise with placebo injections , or placebo injections only . MEASUREMENTS Muscle biopsy specimens were obtained from the vastus lateralis muscle . Isokinetic dynamometry strength tests were used to monitor individual progress and to adjust the weights used in the exercise program . Serum insulin-like growth factor-I ( IGF-I ) was measured and body composition was measured using a Hologic QDR 1000W dual X-ray densitometer . RESULTS The administration of rhGH result ed in significant increase in circulating IGF-I levels in the individuals receiving rhGH treatment . Muscle strength increased significantly in both the rhGH/exercise ( + 55.6 % , P = .0004 ) as well as the exercise alone ( + 47.8 % , P = .0005 ) groups . There was a significant increase in the proportion of type 2 fibers between baseline and six months in the combined rhGH treated subjects versus those not receiving rhGH ( P = .027 ) . CONCLUSIONS Our results are encouraging in that they suggest an effect of growth hormone on a specific aging-correlated deficit . IGF-I was increased by administrating rhGH and muscle strength was increased by exercise . The administration of rhGH to frail older individuals in this study result ed in significant changes in the proportions of fiber types . Whether changes in fiber cross-sectional area or absolute number occur with long-term growth hormone administration requires further study", "The purpose of this study was to investigate the effects of a progressive resistance training program on myosin heavy chain isoform expression , fiber type , and capillarization in patients with symptomatic peripheral arterial disease . Patients were r and omized to either a training group ( n = 11 , mean + /- SD , 70 + /- 6 years , 4 men , 7 women ) or a control group ( n = 9 , 66 + /- 6 years , 5 men , 4 women ) . The training sessions were completed 3 times/week , using 2 sets of various exercises , each performed for 8 - 15 repetitions . Muscle biopsies were obtained before and after 24 weeks from the medial gastrocnemius . Following the 24-week training program , the training group had significantly decreased the percentage of myosin heavy chain type IIB . The proportion of type IIB/AB fibers as measured by using myosin adenosine triphosphatase histochemistry decreased significantly in the training group . There were significant increases in type I and type II fiber areas , and capillary density also increased significantly in the training group . There were significant increases in 10 repetition maximum leg press and calf press strengths in the trained subjects . There were no significant changes in any of the measurements in the control group . It is concluded that progressive resistance training results in significant increases in muscle strength and alters skeletal muscle composition of subjects with peripheral arterial disease", "OBJECTIVE To examine whether improvements in glycemic control and body composition result ing from 6 months of supervised high-intensity progressive resistance training could be maintained after an additional 6 months of home-based resistance training . RESEARCH DESIGN AND METHODS We performed a 12-month r and omized controlled trial in 36 sedentary , overweight men and women with type 2 diabetes ( aged 60 - 80 years ) who were r and omly assigned to moderate weight loss plus high-intensity progressive resistance training ( RT&WL group ) or moderate weight loss plus a control program ( WL group ) . Supervised gymnasium-based training for 6 months was followed by an additional 6 months of home-based training . Glycemic control ( HbA1c ) , body composition , muscle strength , and metabolic syndrome abnormalities were assessed at 0 , 3 , 6 , 9 , and 12 months . RESULTS Compared with the WL group , HbA1c decreased significantly more in the RT&WL group ( -0.8 % ) during 6 months of supervised gymnasium-based training ; however , this effect was not maintained after an additional 6 months of home-based training . In contrast , the greater increase in lean body mass ( LBM ) observed in the RT&WL group compared with the WL group ( 0.9 kg , P upper body and lower body muscle strength in the RT&WL group were maintained over the 12 months ( P body weight , fat mass , fasting glucose , or insulin at 6 or 12 months . CONCLUSIONS In older adults with type 2 diabetes , home-based progressive resistance training was effective for maintaining the gymnasium-based improvements in muscle strength and LBM but not glycemic control . Reductions in adherence and exercise training volume and intensity seem to impede the effectiveness of home-based training for maintaining improved glycemic control", "OBJECTIVE The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility ( LTC ) residents would result in improved function . DESIGN A prospect i ve , r and omized , controlled , semicrossover trial was design ed with participants assigned either to group exercise ( EX ) or recreational therapy ( C ) . In the EX group , the intervention continued for 1 year . In the C group , recreation continued for 6 months ; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months . Functional outcomes were measured at baseline and 3 , 6 , 9 , and 12 months for both groups . SETTING A LTC facility , which included both assisted living ( AL ) and nursing home ( NH ) residents . PARTICIPANTS Twenty frail residents ( 5 from NH , 15 from AL ) aged 75 to 99 years at one LTC facility . INTERVENTION After r and om group assignment , the EX group met 1 hour three times per week . An exercise physiologist and LTC staff conducted sessions which included seated range of motion ( ROM ) exercises and strength training using simple equipment such as elastic resistance b and s ( therab and s ) and soft weights . The C group met three times per week and participated in activities such as painting during the first 6 months , before crossing over to exercise . MEASUREMENTS AND METHODS Objective measures of physical and cognitive function were obtained at baseline and 3 , 6 , 9 , and 12 months using the timed get-up- and -go test ( TUG ) , Berg balance scale , physical performance test ( PPT ) , and mini-mental status exam ( MMSE ) . Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate , a global hypothesis test was used . RESULTS There was a significant overall impact across the four measures of the exercise intervention ( P = 0.013 ) . Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds , which represents an effect size ( in st and ard deviation units ) of 0.50 , increased PPT scores by 1.3 , with effect size = 0.40 , increased Berg scores by 4.8 , with effect size of 0.32 , and increased MMSE by 3.1 , with effect size = 0.54 . Except for the Berg , 90 % confidence intervals on these exercise effects excluded 0 . CONCLUSION Frail elderly in a LTC facility were able to participate and benefit from a strength training program . The program was delivered with low-cost equipment by an exercise physiologist and LTC staff . The advantage of such a program is that it provides recreational and therapeutic benefits ", "Objectives : To investigate whether a 12-week home-based programme of trunk-strengthening exercise could benefit spinal mobility , function and quality of life for osteoporotic and osteopenic postmenopausal women without fracture . Design s : R and omized controlled clinical trial . Setting : Department of Physical Therapy in National Taiwan University Hospital . Subjects : Twenty-eight postmenopausal women ( mean age 60.39=9.3 years ) diagnosed with osteoporosis or osteopenia without fracture history were recruited for this study . Subjects were r and omly assigned into exercise or control groups , each consisting of 14 subjects . Interventions : The 12-week exercise programme included strengthening routines for the trunk extensor and flexor muscles . The subjects performed three sets of 10 repetitions for each of the exercises , with programmes carried out three times per day at home . Main outcome measurements : Muscular strength , spinal range of motion ( ROM ) and motion velocity , Oswestry Disability Question naire ( ODQ ) and quality of life ( QOL ) were measured before the start and after completion of the exercise programme . Results : Statistically significant improvements were demonstrated in spinal ROM and motion velocity in the sagittal and frontal planes for the exercise group ( pB=0.05 ) . Further , the strength of the trunk flexors and extensors increased after exercise training ( pB=0.05 ) . ODQ measure was significantly reduced in the exercise group ( pB=0.05 ) , while the controls showed no significant change . Subjects in the exercise group showed better satisfaction in some domains of the Short-Form-36 Health Survey quality of life question naire ( pB=0.05 ) . Conclusions : This 12-week home-based trunk-strengthening exercise programme could improve trunk mobility and strength , and enhance QOL in osteoporotic and osteopenic postmenopausal women without vertebral fracture . Future study should recruit more cases or more severe subjects to verify the results", "Elderly participants experiencing difficulty in chair rising and with a maximum knee-extensor torque below 87.5 N . m were r and omized to different versions of a strength-training program for the knee-extensors : to a high-guidance group ( HG ; two group sessions supervised by a physical therapist and one unsupervised home session per week , n = 17 ) , a medium-guidance group ( MG ; one supervised group session and two unsupervised home sessions per week , n = 16 ) , or a control group ( C ; no exercise , n = 16 ) . Maximal isometric knee strength increased more in HG than in C ( p = .03 ) and with increasing guidance ( p = .03 ) . The effect was mainly the result of participants with low initial strength . Walking speed increased more for HG than for C ( p = .02 ) and than for MG ( p = .06 ) . No statistically significant improvements were seen on other functional tests . In summary , the study shows a trend toward better results with more supervision , but more and larger studies are needed to confirm this", "We conducted a 2-year ( 42 weeks of consecutive training in each year , separated by 10 weeks of testing and vacation time ) r and omized , controlled trial of weight training in 142 healthy male and female subjects , aged 60 to 80 years . Measurements included dynamic strength , symptom-limited endurance in cycling , treadmill walking and stair climbing , muscle size , and bone mineral density and content of the lumbar spine and whole body . One hundred and thirteen subjects completed the study ( 57 exercise , 56 control ) , with a mean attendance of 85 % among the exercisers . Muscle strength was unchanged in the control subjects but increased ( collapsed across age and gender ) from 32 % ( leg press ) to 90 % ( military press ) in the exercisers . Symptom-limited endurance in cycling , treadmill walking , and stair climbing increased in the exercisers by ( mean + /- SE ) 6.2 + /- 0.8 % , 29.2 + /- 7.3 % , and 57 + /- 12 % , respectively ; the only change in the controls was an unanticipated 33 % increase in stair climbing performance during the first year . These values were unchanged in the controls . Cross-sectional area of the knee extensors increased by 8.7 + /- 0.9 % in the trained subjects and was unchanged in controls . Measures of whole body , lumbar spine bone mineral density , and lumbar spine bone mineral content were unchanged in the exercisers , but whole body bone mineral content decreased by 1 % . In contrast , there were small increases ( bone mineral density among the controls . Long-term weight training proved to be a safe and well-tolerated mode of exercise for the elderly . Increased strength was associated with muscle hypertrophy in each year , and with increased endurance in cycling , walking , and stair climbing . There were no changes in bone mineral density but a small reduction in whole body bone mineral content", "Sayers SP , Bean J , Cuoco A , LeBrasseur NK , Jette A , Fielding RA : Changes in function and disability after resistance training : Does velocity matter ? A pilot study . Am J Phys Med Rehabil 2003;82:605–613 . Objective To compare the effects of high- and low-velocity resistance training on functional performance and disability outcomes in physically limited older women . Design A total of 16 wk of high-velocity resistance training or traditional low-velocity resistance training consisting of knee extension and leg press exercises was performed three times per week by 30 women with self-reported disability to compare their effect on functional performance and disability . Tests of dynamic balance , stair-climb time , chair-rise time , and gait velocity were used to assess changes in functional performance . Changes in disability were assessed using the Medical Outcomes Study Short Form . Results Dynamic balance and stair-climb time improved 8 % and 10 % , respectively , with training . Self-reported disability , physical functioning , role physical , and mental health improved 11 , 9 , and 5 % with training , respectively . There were no significant differences between high- and low-velocity training groups . Conclusions High- and low-velocity training achieved similar improvements in functional performance and disability . Improvements in functional performance and disability were modest compared with robust increases in strength and power . Specific modes of training or behavioral strategies may be necessary to optimize improvements in these outcomes", "Previous studies concerning psychological benefits of exercise among the elderly has focused predominantly on the effects of aerobic exercise . In the present study , psychological and behavioral adaptations in response to 12-weeks of strength training were examined in medically healthy but sedentary 42 older adults ( mean age = 68 years ) . The purpose of this study was to evaluate the effects of high and low intensity resistance training intensity on a ) muscular fitness , b ) psychological affect , and c ) neurocognitive functioning . Subjects were r and omly assigned to high intensity/low volume ( EXH : 2 sets of 8 to 10 repetitions for 75 to 85 % of 1 RM ) , low intensity/high volume ( EXL : 2 sets of 14 to 16 repetitions for 55 to 65 % of 1 RM ) , or no exercise control programs . Prior to and following the 12-week program , subjects underwent comprehensive physiological and psychological evaluations . Physiological assessment included measurements of blood pressure , heart rate , arm and leg muscle strength , body composition , and oxygen consumption ( VO2max ) . Psychological measures included evaluations of mood , anxiety , and physical self-efficacy as well as cognitive functioning . The results of this study indicated that both high and low intensity strength programs were associated with marked improvements in physiological fitness and psychological functioning . Specifically , subjects in the strength training programs increased overall muscle strength by 38.6 % and reduced percent body fat by 3.0 % . Favorable psychological changes in the strength-trained subjects included improvements in positive and negative mood , trait anxiety , and perceived confidence for physical capability . The treatment effects of neurocognitive functioning were not significant . In summary , this study demonstrated that participation in 12-weeks of high or low intensity strength training can improve overall physical fitness , mood , and physical self-efficacy in older adults while cognitive functioning remains constant", "Underst and ing the stress/strain relationship between exercise and bone is critical to underst and ing the potential benefit of exercise in preventing postmenopausal bone loss . This study examined the effect of a 2-year exercise intervention and calcium supplementation ( 600 mg ) on bone mineral density ( BMD ) in 126 postmenopausal women ( mean age , 60 + /- 5 years ) . Assignment was by block r and omization to one of three groups : strength ( S ) , fitness ( F ) , or nonexercise control ( C ) . The two exercise groups completed three sets of the same nine exercises , three times a week . The S group increased the loading , while the F group had additional stationary bicycle riding with minimal increase in loading . Retention at 2 years was 71 % ( 59 % in the S group , 69 % in the F group , and 83 % in the C group ) , while the exercise compliance did not differ between the exercise groups ( S group , 74 + /- 13 % ; F group , 77 + /- 14 % ) . BMD was measured at the hip , lumbar spine , and forearm sites every 6 months using a Hologic 4500 . Whole body BMD also was measured every 6 months on a Hologic 2000 . There was no difference between the groups at the forearm , lumbar spine , or whole body sites . There was a significant effect of the strength program at the total ( 0.9 + /- 2.6 % ; p intertrochanter hip site ( 1.1 + /- 3.0 % ; p strength program in increasing bone density at the clinical ly important hip site . We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies", "& NA ; Phillips , W.T. , and J.R. Ziuraitis . Energy cost of single‐set resistance training in older adults . J. Strength Cond . Res . 18(3):606–609 . 2004.—The purpose of this study was ( a ) to assess the intensity and energy cost of a single‐set resistance training ( RT ) protocol as recommended by the recent American College of Sports Medicine ( ACSM ) guidelines for older adults and ( b ) to compare obtained values to those recently reported as eliciting health benefits via endurance‐based physical activity ( PA ) . Five males and 5 females ( 73.1 ± 5.5 years ) performed 1 set of 15 repetitions of 8 RT exercises while connected to a portable metabolic unit ( CosMed K4b2 ) . The RT intensity ( metabolic equivalents [ METs ] ) was 3.3 ± 0.7 ( males ) and 3.0 ± 0.6 ( females ) . Energy cost ( kcal ) was 84.2 ± 14.6 ( males ) and 69.7 ± 17.4 ( females ) . We conclude that a single‐set 8‐exercise RT protocol may be a feasible alternative for achieving moderate intensity ( 3–6 METs ) for older adults but that additional sets and /or repetitions appear to be necessary to accumulate moderate amounts ( 150–200 kcal ) of PA", "OBJECTIVE . A Phase II trial was performed as a preliminary test of the efficacy and safety of progressive resistance training ( PRT ) as adjunct treatment for rheumatoid cachexia . METHODS Ten mildly disabled patients with well-controlled rheumatoid arthritis ( RA ) trained , on average , 2.5 times per week for 12 weeks . Ten age and sex matched RA patients with similar disease characteristics were non-r and omly assigned to a control group . Body composition , physical function , and disease activity were assessed pre and post intervention period . RESULTS Between group comparisons at followup by ANCOVA using baseline scores as covariate showed significant increases in fat-free mass ( + 1253 g , p = 0.004 ) , total body protein ( + 1063 g , p = 0.044 ) , and arm ( + 280 g , p = 0.005 ) and leg ( + 839 g , p = 0.001 ) lean mass ( a proxy measure of total body skeletal muscle mass ) in response to PRT with no exacerbation of disease activity . There was also a trend for loss of fat mass in the trunk ( -752 g , p = 0.084 ) and a significant reduction in percent body fat ( -1.1 % , p = 0.047 ) . Changes in body composition were associated with improvements in various measures of physical function . CONCLUSION Intense PRT with adequate volume seems to be an effective and safe intervention for stimulating muscle growth in patients with RA . Pending confirmation of these results in a larger r and omized controlled trial that includes patients with more active and severe disease , a similar PRT program should be included in the management of RA as adjunct treatment for cachexia", "The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients . Myopathy , engendered by both heart failure and immunosuppression with glucocorticoids , is a post-transplant complication . The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability . We r and omly assigned patients to either 6 months of resistance exercise ( training group ; n = 8) or a control ( control group ; n = 7 ) group . Exercise was initiated at 2 months after transplant . Biopsy of the right vastus lateralis was performed before and after the 6-month intervention . Myosin heavy chain ( MHC ) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Biochemical assays were performed to determine citrate synthase , 3-hydroxyacyl-CoA-dehydrogenase , and lactate dehydrogenase activity . There were no group differences ( p > or=0.05 ) in MHC composition and enzymatic reserve at baseline . Improvements in the training group for citrate cynthase ( + 40 % ) , 3-hydroxyacyl-CoA-dehydrogenase ( + 10 % ) , and lactate dehydrogenase activity ( + 48 % ) were significantly greater ( p Oxidative type 1 MHC isoform concentration increased significantly in the training group ( + 73 % , p Glycolytic type 2x MHC isoform increased significantly ( 17 % ; p training elicits myofibrillar shifts from less oxidative type II fibers to more oxidative fatigue-resistant type I fibers in heart transplant recipients . Resistance exercise initiated early in the post-transplant period is efficacious in changing skeletal muscle phenotype through increases in enzymatic reserve and shifts in fiber morphology", "The effects of a 16-wk strength-training program on total and regional body composition were assessed by dual-energy X-ray absorptiometry ( DEXA ) , magnetic resonance imaging ( MRI ) , and hydrodensitometry in 13 untrained healthy men [ 60 + /- 4 ( SD ) yr ] . Nine additional men ( 62 + /- 6 yr ) served as inactive controls . The strength-training program result ed in substantial increases in both upper ( 39 + /- 8 % ; P lower ( 42 + /- 14 % ; P body strength . Total fat-free mass ( FFM ) increased by 2 kg ( 62.0 + /- 7.1 to 64.0 + /- 7.2 kg ; P total fat mass decreased by the same amount ( 23.8 + /- 6.7 to 21.8 + /- 6.0 kg ; P FFM ( 61.3 + /- 7.8 to 63.0 + /- 7.6 kg ; P fat mass ( 23.8 + /- 7.9 to 22.1 + /- 7.7 kg ; P FFM was increased in the arms ( 6.045 + /- 0.860 to 6.418 + /- 0.803 kg ; P fat mass was reduced in the arms ( 2.383 + /- 0.830 to 2.128 + /- 0.714 kg ; P < 0.01 ) , legs ( 7.583 + /- 1.675 to 6.945 + /- 1.551 kg ; P < 0.001 ) , and trunk ( 12.216 + /- 4.143 to 11.281 + /- 3.653 kg ; P < 0.01 ) as a result of training . ( ABSTRACT TRUNCATED AT 250 WORDS", "QUESTIONS Does a 12-week , predominantly home-based program of progressive resistance exercises reduce impairments , activity limitations , and participation restrictions in people with chronic obstructive pulmonary disease ? Are any gains maintained 12 weeks after the cessation of the program ? DESIGN R and omised controlled trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 54 people with moderately severe chronic obstructive pulmonary disease not undergoing pulmonary rehabilitation . INTERVENTION The experimental group performed six progressive resistance exercises three times per week ( once a week hospital-based , twice a week home-based ) for 12 weeks . Exercise intensity was three sets of 8 to 12 repetition maximum progressed against elasticised b and s of increasing resistance . The control group received no intervention . OUTCOME MEASURES Primary outcomes were strength ( knee extensor , hip abductor , shoulder horizontal flexor , shoulder flexor ) measured using h and -held dynamometry , and walking capacity measured by the 6-minute Walk Test performed before and after intervention and again at 12 weeks after the cessation of intervention . RESULTS The experimental group increased their knee extensor strength by 4.9 kg ( 95 % CI 1.1 to 8.7 ) more than the control group by Week 12 . However , this gain was not maintained at Week 24 . No difference between the groups was found for any of the other primary outcomes . CONCLUSIONS A predominantly home-based progressive resistance exercise program led to modest improvements in knee extensor strength in people with chronic obstructive pulmonary disease . However , 44 % of the experimental group were unable to complete the exercise program , highlighting the need to underst and factors influencing adherence to exercise in this population", "Background and aims : Physical exercise is associated with a lower risk of disability . The impact of comorbidity on the benefits from physical exercise has not been clearly investigated . Elders with comorbidity may benefit from physical exercise to preserve physical function . Methods : Data are from 435 participants with knee osteoarthritis aged ≥60 years enrolled in the Fitness and Arthritis in Seniors Trial ( FAST ) , who were r and omly assigned to 18-month health educational ( HE ) , weight training ( WT ) , or aerobic exercise ( AE ) interventions . Comorbidity was defined as the presence of osteoarthritis and ≥2 clinical conditions . Percent changes in the 6-minute walk test , self-reported disability and knee pain from baseline to 3- , 9- , and 18-month follow-up visits were analyzed according to comorbidity , using analysis of variance . Significance s were adjusted using the Bonferroni method . Results : Mean age of the sample was 68.7 years . In participants with comorbidity ( n=197 ) , those in the AE intervention showed significant improvement in walking speed , compared to WT and HE groups , since the beginning of follow-up . Subjects with comorbidity in AE and WT groups showed improvement of the disability score at the 3-month follow-up visit compared to those in the HE group . This improvement was maintained at the end of the follow-up by the only AE group compared to the HE one ( p=0.06 ) . In participants with comorbidity , the pain score was improved by the AE intervention . Conclusions : AE and WT interventions improve physical function in individuals with comorbidity . AE improves physical function and knee pain independently of the presence of comorbidity", "OBJECTIVE The aim of this study was to evaluate the effect of a 10-week , high-intensity strength-training program targeting key lower extremity muscles for the purpose of improving postural control in balance-impaired older adults . METHODS A quasi-experimental , delayed entry controlled design was used to evaluate balance ability in balance-impaired older adults after participation in 10 weeks of high-intensity strength training focused on the quadriceps , hamstrings , tibialis anterior , and gastrocnemius muscles . Participants were evaluated using vali date d clinical measures of functional balance ability : the Berg Balance Scale , the Timed Up and Go , and the Activities-Specific Balance Confidence Scale . RESULTS After strength training , the exercisers were significantly stronger than the control subjects . They improved significantly on the Berg Balance Scale ( P = .030 ) from a mean score of 48.8 + /- 2.4 of 56 before training to 51.2 + /- 4.3 of 56 after training . The Timed Up and Go ( P = .045 ) and the Activities-Specific Balance Confidence Scale ( P = .038 ) also improved significantly in the experimental group . These changes are associated with a decrease in fall risk . CONCLUSIONS High-intensity strength training can safely and effectively strengthen lower extremity muscles in balance-impaired older adults , result ing in significant improvements in functional balance ability and decreased fall risk", "This study was design ed to assess the effects of 18 months of resistance exercise on regional and total bone mineral density ( BMD ) and soft tissue lean mass ( STL ) in premenopausal women aged 28 - 39 r and omly assigned to an exercise or control group . Twenty-two exercise and 34 control subjects completed the 18-month training study . All subjects were previously inactive and untrained women . Initial , 5- , 12- and 18-month assessment s were made of total and regional BMD and total and regional STL using dual energy X-ray absorptiometry . All subjects consumed a 500 mg/day elemental calcium supplement throughout the study . Initial Ca intake without supplement averaged 1,023 mg/day in total sample . Serum levels of bone osteocalcin and dietary assessment s using 12 r and omly assigned days of diet records were also completed . Muscular strength was assessed from both 1 repetition maximum ( RM ) testing of 10 weightlifting exercises and by peak torque for hip abduction/adduction and knee extension/flexion . Training increased strength by 58.1 % based on 1 RM testing and by 33.8 % based on isokinetic testing at 18 months versus baseline . BMD increased significantly above baseline at the lumbar spine for the exercise group at 5 months ( 2.8 % ) , 12 months ( 2.3 % ) , and 18 months ( 1.9 % ) as compared with controls . Femur trochanter BMD increased significantly ( p total BMD , arm BMD , or leg BMD were found . There was a 20 % increase in BGP in the exercise group as compared with controls at 5 months and this difference was maintained throughout the study . For STL , significant increases for total , arm , and leg were found at 5 , 12 , and 18 months for the exercise group versus control ranging from 1 - 6 % over baseline . These results support the use of strength training for increasing STL and muscular strength with smaller but significant regional increases in BMD in the premenopausal population", "OBJECTIVES Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment and a strong predictor of functional performance . We tested the hypothesis that a high-velocity resistance-training program ( HI ) would increase muscle power more than a traditional low-velocity resistance-training program ( LO ) . DESIGN R and omized controlled trial . SETTING University-based human physiology laboratory . PARTICIPANTS Thirty women with self-reported dis-ability ( aged 73 + 1 , body mass index 30.1 + 1.1 kg/mn ) . INTERVENTION We conducted a r and omized trial comparing changes in skeletal muscle power and strength after 16 weeks of HI or LO . Training was performed three times per week , and subjects completed three sets ( 8 - 10 repetitions ) of leg press ( LP ) and knee extension ( KE ) exercises at 70 % of the one-repetition maximum ( IRM ) . MEASUREMENTS One-repetition maximum ( 1 RM ) and peak power for KE and LP . RESULTS LP and KE relative training force and total work were similar between groups ( P > .05 ) . However , HI generated significantly higher power during training sessions than LO for LP ( 3.7-fold greater , P LP and KE 1RM muscle strength increased similarly in both groups asa result of the training ( P LP peak power increased significantly more in HI than in LO ( 267 W vs 139 W , P improvement in LP power at 40 % , 50 % , 60%,70 % , 80 % , and 90 % of the 1 RM than did LO ( P 1RM strength similarly and was more effective in improving peak power than was traditional LO in older women . Improvements in lower extremity peak power may exert a greater influence on age-associated reductions in physical functioning than other exercise interventions", "The present investigation attempted to determine whether resistance exercise intensity affects flexibility and strength performance in the elderly following a 6-month resistance training and detraining period . Fifty-eight healthy , inactive older men ( 65–78 yrs ) were r and omly assigned to 1 of 4 groups : a control group ( C , n = 10 ) , a low-intensity resistance training group ( LI , n = 14 , 40 % of 1 repetition maximum [ 1RM ] ) , a moderate-intensity resistance training group ( MI , n = 12 , 60 % of 1RM ) , or a high-intensity resistance training group ( HI , n = 14 , 80 % of 1RM ) . Subjects in exercise groups followed a 3 days per week , whole-body ( 10 exercises , 3 sets per exercise ) protocol for 24 weeks . Training was immediately followed by a 24-week detraining period . Strength ( bench and leg press 1RM ) and range of motion in trunk , elbow , knee , shoulder , and hip joints were measured at baseline and during training and detraining . Resistance training increased upper-(34 % in LI , 48 % in MI , and 75 % in HI ) and lower-body strength ( 38 % in LI , 53 % in MI , and 63 % in HI ) in an intensity-dependent manner . Flexibility demonstrated an intensity-dependent enhancement ( 3–12 % in LI , 6–22 % in MI , and 8–28 % in HI ) . Detraining caused significant losses in strength ( 70–98 % in LI , 44–50 % in MI , and 27–29 % in HI ) and flexibility ( 90–110 % in LI , 30–71 % in MI , and 23–51 % in HI ) in an intensity-dependent manner . Results indicate that resistance training by itself improves flexibility in the aged . However , intensities greater than 60 % of 1RM are more effective in producing flexibility gains , and strength improvement with resistance training is also intensity-dependent . Detraining seems to reverse training strength and flexibility gains in the elderly in an intensity-dependent manner", "The present study was design ed to identify prospect ively the individual chronic characteristics associated with falling among elderly persons and to test the hypothesis that risk of falling increases as the number of chronic disabilities increases . Seventy-nine consecutive admissions to three intermediate care facilities were evaluated . Twenty-five of the subjects became recurrent fallers . The nine risk factors included in the fall risk index were mobility score , morale score , mental status score , distant vision , hearing , postural blood pressure , results of back examination , postadmission medications , and admission activities of daily living score . A subject 's fall risk score was the number of index factors present . The proportions of recurrent fallers increased from 0 percent ( 0 of 30 ) in those with 0 to three risk factors , to 31 percent ( 11 of 35 ) in those with four to six factors , to 100 percent ( 14 of 14 ) in those with seven or more factors . Falling , at least among some elderly persons , appears to result from the accumulated effect of multiple specific disabilities . Some of these disabilities may be remediable . The mobility test , the best single predictor of recurrent falling , may be useful clinical ly because it is simple , recreates fall situations , and provides a dynamic , integrated assessment of mobility", "Objectives —There is a paucity of long term studies on exercise training in elderly women . The purpose of this study was to investigate the effects of one year of progressive resistance exercise ( PRE ) on dynamic muscular strength and the relations to bone mineral density ( BMD ) in elderly women . Methods —Forty four healthy sedentary women ( mean age 68.8 years ) volunteered for this study and were r and omly assigned to either an exercise group or a control group . The exercise group were involved in three one hour sessions a week for 52 weeks of supervised PRE to strengthen the large muscle groups of the body , while the control group were instructed to continue their normal lifestyle . The exercise circuit included three sets of eight repetitions at 75 % of one repetition maximum focused on the large muscle groups . BMD was measured by dual energy x ray absoptiometry ( Lunar DPX ) at the lumbar spine and at three sites in the proximal femur . Other selected parameters of physical fitness were also measured . Results —Statistical analyses ( analysis of covariance ) showed significant strength gains ( p bilateral bench press ( > 29 % ) , bilateral leg press ( > 19 % ) , and unilateral biceps curl ( > 20 % ) . No significant difference between groups was evident in body weight , grip strength , flexibility , waist to hip ratio , or the sum of eight skinfolds . Significant relations ( p dynamic leg strength and the BMD of the femoral neck , Ward 's triangle , and the lumbar spine . Conclusions —Significant strength changes , after one year of PRE , were evident in elderly women , and the muscle increases may parallel changes in BMD ; however , correlation coefficients were moderate", "The purpose of this study was to evaluate the effects of a 24-month moderate-intensity resistive-training intervention on strength and function in older adults . A repeated- measures experimental research design was employed as a sample of 55 apparently healthy , older , community-dwelling volunteers ( 30 exercisers- 25 women and 5 men ; 25 comparisons- 16 women and 9 men ) were evaluated for strength of 5 muscle groups that influence lower extremity movement and physical function . Strength and function were evaluated at 6-month intervals . The findings from this study indicate that a moderate-intensity resistive-training program increases strength in older adults and that the strength benefits are retained for the duration of the intervention . Furthermore , a long-term strength-training program can increase independent-function skills in older adults and might therefore aid in prolonging functional independence", "PURPOSE The purpose of this study was to determine , in a r and omized clinical trial of 439 individuals with knee osteoarthritis , the incremental cost-effectiveness of aerobic versus weight resistance training , compared with an education control intervention . METHODS Cost estimates of the intervention were based upon the cost of purchasing from the community similar services to provide exercise or health education . Effect at 18 months was measured using several variables , including : self-reported disability score , 6-min walking distance , stair climb , lifting and carrying task , car task , and measures of pain frequency and pain intensity on ambulation and transfer . RESULTS The total cost of the educational intervention was $ 343.98 per participant . The aerobic exercise intervention cost $ 323.55 per participant , and the resistance training intervention cost $ 325.20 per participant . On all but two of the outcome variables , the incremental savings per incremental effect for the resistance exercise group was greater than for the aerobic exercise group . CONCLUSION The data obtained from this study suggest that , compared with an education control , resistance training for seniors with knee osteoarthritis is more economically efficient than aerobic exercise in improving physical function . However , the magnitude of the difference in efficiency between the two approaches is small", "BACKGROUND Pharmacological treatment of depression in geriatric patients is often difficult . Although unsupervised exercise has been shown to benefit younger depressed patients , there is no evidence that unsupervised exercise can be used as a maintenance treatment for depression in elderly patients . Our aim was to test the feasibility and efficacy of unsupervised exercise as a long-term treatment for clinical depression in elderly patients . METHODS We studied 32 subjects ( 71.3 + /- 1.2 years of age , mean + /- SE ) in a 20-week , r and omized , controlled trial , with follow-up at 26 months . Subjects were community-dwelling patients with major or minor depression or dysthymia . Exercisers engaged in 10 weeks of supervised weight-lifting exercise followed by 10 weeks of unsupervised exercise . Controls attended lectures for 10 weeks . No contact was made with either group after 20 weeks until final follow-up . Blinded assessment was made with the Beck Depression Inventory ( BDI ) , the Philadelphia Geriatric Morale Scale , and Ewart 's Self Efficacy Scale at 20 weeks and with the BDI and physical activity question naire at 26 months . RESULTS Patients r and omized to the exercise condition completed 18 + /- 2 sessions of unsupervised exercise during Weeks 10 to 20 . The BDI was significantly reduced at both 20 weeks and 26 months of follow-up in exercisers compared with controls ( p weight lifting , versus 0 % of controls ( p Unsupervised weight-lifting exercise maintains its antidepressant effectiveness at 20 weeks in depressed elderly patients . Long-term changes in exercise behavior are possible in some patients even without supervision", "OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people", "OBJECTIVE To compare the effects of concentric and coupled concentric-eccentric isokinetic resistance training on functional capacity and symptoms of patients with osteoarthrosis ( OA ) of both knees . DESIGN Repeated measures . SETTING A university exercise physiology laboratory . PARTICIPANTS Twenty-three volunteers , ages 41 to 75 years . Patients were r and omly assigned to 3 groups : concentric ( CON , n = 9 ) , concentric-eccentric ( CON-ECC , n = 8) , and nontreatment ( NONTX , n = 6 ) . INTERVENTIONS The CON group performed 12 concentric contractions of each knee extensor and flexor muscles ; the CON-ECC group performed 6 concentric and 6 eccentric contractions of each knee muscle group by using a spectrum of angular velocities ranging from 30 degrees/s to 180 degrees/s with 30 degrees/s intervals , for both sides , 3 days a week for 8 weeks . MAIN OUTCOME MEASURES Functional capacity ( rising from a chair , walking , stair climbing and descending ) and pain during rest and activities , peak torque , and cross-sectional area ( CSA ) of knee muscle groups of subjects were tested before and after training . RESULTS Both training groups showed marked decreases ( P pain scores and increases ( P functional capacity together with increases ( P peak torque and CSA of knee muscles . However , the NONTX group did not display these marked changes after the 8-week period . The results also indicated that concentric-eccentric training has a greater influence on functional capacity , especially stair climbing and descending , than that of concentric training when compared with NONTX group ; however , the improvements in pain measurements were better in the CON group compared with the CON-ECC group after the training . CONCLUSIONS The results suggest that with the isokinetic resistance training used in this study , it is possible to improve functional capacity and decrease pain in patients with OA of the knee . The results also showed that extensive training involving a high number of repetitions and eccentric contractions was safe , effective , and well tolerated for the patients with knee OA", "OBJECTIVES This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities . METHODS A r and omized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group . Assessment s were conducted at baseline and at 3 and 6 months following r and omization . The program consisted of videotaped exercise routines performed with elastic b and s of varying thickness . RESULTS High rates of exercise adherence were achieved , with 89 % of the recommended exercise sessions performed over 6 months . Relative to controls , subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6 % to 12 % , a 20 % improvement in t and em gait , and a 15 % to 18 % reduction in physical and overall disability at the 6-month follow-up . No adverse health effects were encountered . CONCLUSIONS These findings provide important evidence that home-based resistance exercise programs design ed for older persons with disabilities hold promise as an effective public health strategy", "Most studies that assess the effects of exercise in the elderly involve subjects who are in good health . The objective of this prospect i ve longitudinal study was to examine the impact of exercise on cardiovascular fitness , flexibility , and strength in an elderly population that included chronically ill individuals . Patients were recruited initially from a population of veterans over 64 years of age who use a VA outpatient clinic as their regular source of care . The exercise intervention consisted of 90 minutes of exercise 3 days per week at 70 % of the patient 's maximal capacity . Activities included stationary cycling , stretching , weight training , and walking . Of 69 patients who began the program , 49 ( 71 % ) reached 4-month follow-up . Most patients completing follow-up ( 76 % ) had at least one chronic disease , such as arthritis , hypertension , or heart disease . Patients who dropped out were more likely to have multiple chronic illnesses than those who remained in the program . Average weekly attendance was 65 % and was stable over time . Improvements in cardiovascular fitness at 4-month follow-up were significant : Metabolic equivalents increased from 7.1 + /- 2.3 to 8.3 + /- 2.6 ( P less than .001 ) , treadmill time increased from 8.5 + /- 3.8 to 11.2 + /- 4.2 minutes ( P less than .001 ) , submaximal heart rate decreased from 123.7 + /- 18.8 to 118.8 + /- 19.4 beats per minute ( P less than .001 ) and resting heart rate decreased from 68.1 + /- 10.6 to 63.3 + /- 11.6 beats per minute ( P = .005 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "Skeletal muscle adaptations to high intensity knee extensor strength and /or endurance training in patients with chronic heart failure were investigated . Eleven patients with chronic heart failure were r and omized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks . After training , the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 ( 32 ) to 114 ( 40 ) watts ( W , P Peak dynamic knee extensor work rate showed the greatest increase after endurance training ( 40 % , P Maximal dynamic and isometric strength were elevated by 40 - 45 % ( P strength training . The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs ( 9 % , P capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58 % in the endurance-trained legs ( P oxidative enzyme activity in m. vastus lateralis was significantly raised above 50 % after endurance training , whereas glycolytic enzyme activity was unaltered . The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training . This results in a marked rise in local , and a small rise in total work capacity , indicating maintained plasticity of skeletal muscle in chronic heart failure patients", "OBJECTIVES This investigation examined the effect of 6 months of high- or low-intensity resistance exercise on muscular strength and endurance and stair climbing ability in adults aged 60 to 83 . DESIGN A r and omized controlled trial . SETTING University of Florida Center for Exercise Science . PARTICIPANTS Sixty-two men and women completed the study protocol . Subjects were matched for strength and r and omly assigned to a control ( n = 16 ) , low-intensity ( LEX , n = 24 ) , or high-intensity ( HEX , n = 22 ) group . INTERVENTION Six months of progressive , whole-body resistance training . Subjects trained at 50 % of their one-repetition maximum ( 1RM ) for 13 repetitions ( LEX ) or 80 % of 1RM for eight repetitions ( HEX ) three times per week for 24 weeks using resistance machines . One set each of 12 exercises was performed . MEASUREMENTS One-repetition maximum was measured for eight different exercises . Muscular endurance was measured using leg press and chest press machines . Low back strength was measured using a lumbar extension machine . Stair climbing ability was assessed as the time to ascend one flight of stairs . RESULTS 1RM significantly increased for all exercises tested for the HEX and LEX groups ( P total strength ( sum of all eight 1RMs ) were 17.2 % and 17.8 % for the LEX and HEX groups , respectively . Muscular endurance improved by 79.2 % and 105.0 % for the leg press , and 75.5 % and 68.0 % for the chest press for the LEX and HEX groups , respectively . The time to ascend one flight of stairs significantly decreased for both the LEX and HEX groups ( P Lumbar extension strength increased by 62.6 % and 39.5 % for the LEX and HEX groups , respectively . CONCLUSIONS These data indicate that significant and similar improvements in strength , endurance , and stair climbing time can be obtained in older adults as a consequence of high- or low-intensity resistance exercise training . These findings may have an effect on how resistance exercise is prescribed to older adults", "OBJECTIVES This paper describes a videotaped , home-based , strength training program , titled Strong-for-Life and reports on its effectiveness in improving muscle strength , psychological well-being , and health status in a sample of older persons . DESIGN AND SETTING We enrolled 102 nondisabled , community-dwelling older people aged 66 to 87 , identified from the Medicare beneficiary list , into a r and omized , controlled trial . MEASUREMENTS Effectiveness was based on change in isokinetic upper and lower extremity muscle strength , psychologic well-being , and health status . RESULTS Results revealed several statistically significant short-term benefits after 12 to 15 weeks of exercise , especially for men . Younger older adults demonstrated a 10 % improvement in knee extensor strength relative to control subjects . Older male exercisers achieved significant differences relative to controls in perceived anger , tension , and overall social functioning . Male exercisers , in general , achieved significant improvement in perceived vigor . Women did not report psychological benefits following participation in the program . CONCLUSION Study results reveal that the Strong for Life program , design ed to be widely disseminated to the nondisabled older population , has many short-term positive benefits", "Increasing physical activity is often prescribed to improve blood lipids ; however , the efficacy of exercise in improving blood lipids in older adults is not clear . The objective of this study was to examine the effects of different exercise modes on blood lipid levels in previously sedentary older adults engaging in a 16-week exercise intervention . One hundred thirty-one subjects ( mean age 74.6+/-6 years ) were r and omly assigned to a resistance training group , aerobic walking group , combined exercise group , or nonexercising control group . Blood lipids were measured at baseline , 8 weeks , and postintervention . Exercise mode did not impact blood lipids . All groups had lower lipid levels over time . Total cholesterol , low- and high-density lipoprotein , and triglycerides were significantly lower . The decrease in all groups , including the controls , may be due to a seasonal effect in older adults that has been documented in younger individuals", "The purpose of this study was to determine the influence of simple , progressive lower body exercise training , focusing on strength and power , on functional abilities in frail older adults . Twenty-five residents of a long-term care facility ( 75 - 94 yrs ) participated in this r and omized controlled trial of 10-wks duration . The exercise group ( Ex , n = 18 ) underwent simple , progressive lower body resistance exercises , specifically aim ed at improving muscle power , 3 times/wk ; the control subjects ( Con , n = 7 ) maintained their usual daily activities . Knee extensor strength and power were measured on an isokinetic dynamometer ( 180 degrees/s ) , and functional performance was assessed from a 6-m walk timed test , a 30-s chair st and , and an 8-ft up- and -go timed test , before and after the 10-wk intervention period . Significant increases were found in the Ex group for eccentric ( 44 % ) and concentric ( 60 % ) average power ( p functional test : the 8-foot up- and -go , chair st and , and walk time improved by 31 % , 66 % , and 33 % , respectively ( p No significant change occurred in the Con group . In conclusion , simple progressive exercise training , even in the 10th decade , increases muscle power and is associated with an improved performance of functional activities using the trained muscles", "Background and aims : An acute illness may place older frail people at increased risk of losing independence in functional abilities . Physical exercise may reduce the risk by improving muscle strength and balance . However , the effects of physical training on functional abilities have not been studied among frail , very old people recovering from an acute illness . The aim of this study was to determine the effects of a group-based exercise program on their ability to carry out self-care ( ADL ) and instrumental activities ( IADL ) relevant to daily life after discharge from hospital . Methods : This r and omized controlled trial examined 68 community-dwelling women aged 75 years or older ( mean age 83.0 , SD 3.9 ) who were hospitalized due to an acute illness , and were mobility-impaired at admission . Participants were recruited from the geriatric ward of a primary -care health-center hospital , and were r and omized into group-based strength training ( n=34 ) and control ( n=34 ) groups . The 10-week group-based intervention included strength training and functional exercises . The control group received instructions for a home exercise training program , including functional exercises but no further encouragement to exercise . The level of independence in ADL and IADL was evaluated , using a 13-item scale with stepwise grading from fully independent to fully dependent . Measurements took place immediately before and after the intervention , and three and nine months later . Results : The intervention did not have any significant main effect ( p=0.407 ) , nor was there any significant interaction between follow-up time and intervention ( p=0.854 ) . Conclusions : The multi-component outpatient strength training program did not improve autonomy in expert-evaluated ADL/IADL functions", "The effects of 12 wk of progressive resistance strength training on in vivo and in vitro immune parameters were evaluated in a controlled study of eight subjects with rheumatoid arthritis ( RA ) , eight healthy young ( 22 - 30 yr ) , and eight healthy elderly ( 65 - 80 yr ) individuals . Six healthy elderly ( 65 - 80 yr ) nontraining control subjects were also evaluated to account for seasonal and psychosocial effects . Training subjects exercised at 80 % of their one-repetition maximum and performed eight repetitions per set , three sets per session on a twice weekly basis . Peripheral blood mononuclear cell ( P BMC ) sub population s , cytokine and prostagl and in ( PG ) E2 production , proliferative response , and delayed type hypersensitivity ( DTH ) skin response were measured before and after 12 wk of training . Training did not induce changes in P BMC subsets , interleukin (IL)-1 beta , tumor necrosis factor-alpha ( TNF ) , IL-6 , IL-2 , or PGE2 production , lymphocyte proliferation , or DTH response in any of the training groups , compared with control subjects . These data suggest that 12 wk of high-intensity progressive resistance strength training does not affect immune function in young or elderly healthy individuals or subjects with RA", "PURPOSE The main purpose of this study was to analyze the impact of a 1-yr resistance-training program on body composition and muscle strength in postmenopausal women , and to describe the impact of hormone replacement therapy ( HRT ) on body composition changes , with and without exercise . Secondarily , we wanted to study dose-response relationships between measures of program compliance and changes in primary outcomes . METHODS Subjects were postmenopausal women ( 40 - 66 yr ) r and omly assigned to an exercise ( EX ) group ( N = 117 ) and a nonexercise group ( N = 116 ) . The EX group participated in a 1 yr trainer-supervised resistance-training program , 60 - 75 min.d-1 , 3 d.wk-1 . Lean soft tissue ( LST ) and fat tissue ( FT ) changes were measured by dual-energy x-ray absorptiometry and strength by one-repetition maximum testing . RESULTS Significant ( P LST were observed for women who exercised , regardless of HRT status , whereas women who did not exercise lost LST ( P FT losses were observed for women who exercised while on HRT ( P Strength increases were observed at all sites ( P Total weight lifted by subjects in their training sessions was a significant predictor of changes in LST ( P strength ( P total and regional body composition in postmenopausal women by increasing LST in all women and decreasing FT in women on HRT . Hormone therapy showed no independent effects on body composition , but it protected nonexercising women from losses in LST . The lean and muscle strength changes observed were partially dependent on the volume of training , as expressed by attendance and total weight lifted in 1 yr of training", "Background : Data regarding the effect of exercise programmes on older adults ’ health-related quality of life ( HRQOL ) and habitual physical activity are inconsistent . Objective : To determine whether a functional tasks exercise programme ( enhances functional capacity ) and a resistance exercise programme ( increases muscle strength ) have a different effect on the HRQOL and physical activity of community-dwelling older women . Methods : Ninety-eight women were r and omised to a functional tasks exercise programme ( function group ) , a resistance exercise programme ( resistance group ) , or normal activity group ( control group ) . Participants attended exercise classes three times a week for 12 weeks . The SF-36 Health Survey question naire and self-reported physical activity were obtained at baseline , directly after completion of the intervention ( 3 months ) , and 6 months later ( 9 months ) . Results : At 3 months , no difference in mean change in HRQOL and physical activity scores was seen between the groups , except for an increased SF-36 physical functioning score for the resistance group compared with the control group ( p = 0.019 ) and the function group ( p = 0.046 ) . Between 3 and 9 months , the self-reported physical functioning score of the function group decreased to below baseline ( p = 0.026 ) , and physical activity ( p = 0.040 ) decreased in the resistance group compared with the function group . Conclusions : Exercise has a limited effect on the HRQOL and self-reported physical activity of community-living older women . Our results suggest that in these subjects HRQOL measures may be affected by ceiling effects and response shift . Studies should include performance-based measures in addition to self-report HRQOL measures , to obtain a better underst and ing of the effect of exercise interventions in older adults", "OBJECTIVE To assess immediate and near-term effects of 2 exercise training programs for persons with idiopathic Parkinson 's disease ( IPD ) . DESIGN R and omized control trial . SETTING Public health facility and medical center . PARTICIPANTS Fifteen persons with IPD . INTERVENTION Combined group ( balance and resistance training ) and balance group ( balance training only ) underwent 10 weeks of high-intensity resistance training ( knee extensors and flexors , ankle plantarflexion ) and /or balance training under altered visual and somatosensory sensory conditions , 3 times a week on nonconsecutive days . Groups were assessed before , immediately after training , and 4 weeks later . MAIN OUTCOME MEASURES Balance was assessed by computerized dynamic posturography , which determined the subject 's response to reduced or altered visual and somatosensory orientation cues ( Sensory Orientation Test [ SOT ] ) . Muscle strength was assessed by measuring the amount of weight a participant could lift , by using a st and ardized weight- and -pulley system , during a 4-repetition-maximum test of knee extension , knee flexion , and ankle plantarflexion . RESULTS Both types of training improved SOT performance . This effect was larger in the combined group . Both groups could balance longer before falling , and this effect persisted for at least 4 weeks . Muscle strength increased marginally in the balance group and substantially in the combined group , and this effect persisted for at least 4 weeks . CONCLUSION Muscle strength and balance can be improved in persons with IPD by high-intensity resistance training and balance training", "Physical disability is common among older persons living within the community . The Framingham Disability Study [ 1 , 2 ] reported that , among community-dwelling persons older than 70 years of age , 49 % of women and 27 % of men have substantial mobility or work limitations . More recently , a 4-year prospect i ve trial of healthy elderly persons with no disability at baseline showed that lower-extremity physical performance at baseline was highly predictive for the subsequent development of disability [ 3 ] . Muscle mass , strength , and endurance decrease with age , and a close correlation between short-course walking speed and the size and strength of leg muscles has been shown in institutionalized nonagenarians [ 4 ] . Furthermore , resistance training in this population has been shown to result in increased measures of physical performance and corresponding increases in muscle strength , size , and short-course walking speed [ 4 , 5 ] . Our goal was to determine whether resistance training would improve walking endurance and lower-limb strength in nondisabled , community-dwelling elderly persons . Methods Twenty-four sedentary , healthy persons ( 11 men and 13 women ) were r and omly assigned within sex groups either to a 12-week resistance-training program or to sedentary control status . The mean age of the participants was 70.4 4 years ( range , 65 to 79 years ) , and no differences in mean age were seen between groups ( 69.9 4 years in the resistance-training group ; 70.7 5 years in the control group [ P > 0.2 ] ) . The resistance-training group was composed of 6 men and 6 women ; the control group consisted of 5 men and 7 women . Participants did symptom-limited treadmill stress tests at baseline , and we collected expired gas to determine peak aerobic capacity . We used a Horizon Metabolic Measurement Cart ( Sensormedics , Yorba Linda , California ) to analyze expired air . Participants were excluded if they had angina or electrocardiographic ischemia ( defined as ST-segment depression more than 1 mm ) during the exercise test ( n = 2 ) , if their resting blood pressure was higher than 160/90 mm Hg ( n = 4 ) , or if they had a noncardiopulmonary limitation of exercise capacity , such as claudication , arthritis , or cerebrovascular disease ( n = 1 ) . We tested 29 participants to arrive at the final study sample of 24 persons . No participants were receiving calcium- or -blocking medications or estrogen-replacement therapy , and none had diabetes . We determined body composition by using underwater weighing and correcting for residual volume [ 6 ] . Leg-muscle mass was determined by dual-energy x-ray absorptiometry [ 7 ] . Strength was evaluated on a Universal Gym apparatus ( Universal , Cedar Rapids , Iowa ) by measuring the single repetition maximal lift for leg extension , leg flexion , and bench press . We measured submaximal endurance capacity on the treadmill by first having participants walk for 5 minutes at an intensity of 50 % of their previously determined peak aerobic capacity . Participants then gradually increased their walking intensity to 80 % of peak aerobic capacity by 10 minutes of the continuous protocol and proceeded until exhaustion ( n = 24 ) or 45 minutes , at which time the test was terminated . Because none of the participants had angina , claudication , or exercise-limiting arthritis , exhaustion was defined as a combination of leg fatigue , dyspnea , and overall body fatigue . During endurance testing , heart rate , blood pressure , oxygen uptake , and perceived exertion [ 8 ] were measured at 5-minute intervals until exhaustion . After 12 weeks , variables were measured again , and walking endurance was measured at the same absolute workload as before conditioning . The weight-training regimen consisted of three sets of eight repetitions of seven exercises done using a Universal Gym apparatus 3 days per week . The exercises ( and primary muscles exercised ) were leg extension ( quadriceps ) , leg curl ( hamstrings ) , arm extension ( triceps ) , arm curl ( biceps ) , lateral pull-down ( latissimus dorsi and biceps ) , bench press ( pectoralis major and triceps ) , and squat ( gluteals and quadriceps ) . A rest period of 1 to 2 minutes was taken between sets . The participants began at a resistance of 50 % of their single repetition maximum . The resistance was then increased progressively until participants were exercising at 80 % of their single repetition maximum by week 9 . Strength was retested intermittently , and the training loads were adjusted as required . The participants did not train aerobically . Controls were instructed not to alter their home activity habits . A two-factor analysis of variance was done on baseline measures , with sex and training groups as the factors [ 9 ] . Women differed from men in baseline measures of fitness , strength , and body composition , but no sex-group interactions were seen . Pre- to postconditioning measures were analyzed using repeated-measure analysis of variance with results separated by sex . Data collected during the submaximal endurance study were analyzed for perceived exertion , heart rate , and systolic blood pressure ( excluding rest and exhaustion values ) by repeated-measure analysis of variance . Relations between variables were studied by linear regression analysis . Data are presented as mean SD . Analyses were done using BMDP New System for Windows , Version 1.0 ( BMDP Statistical Software , Los Angeles , California ) . Results After the 12-week resistance-training program , strength increased substantially in the resistance-training group . The single repetition maximums increased by 29 % 24 % for leg extension , 65 % 79 % for leg flexion , and 29 % 15 % for bench press . When results were analyzed separately by sex and compared with results in controls , single repetition maximums for leg extension increased significantly among women ( P single repetition maximums for bench press increased significantly among women ( P single repetition maximums for leg flexion compared with controls ( P control group showed no change in strength measures over the 12-week period , and the strength changes for each of the exercises in the intervention group when sexes were combined were significantly greater than the measures in the controls ( P Resistance-Training and Control Groups at Baseline and 12 Weeks Women in our study had lower measures of peak aerobic capacity at baseline than men ( 21.5 1.1 mL/kg min1 compared with 28.8 1.5 mL/kg min1 ; P = 0.03 ) and lower measures of strength as measured by single repetition maximum for leg extension ( 23.5 1.0 kg compared with 42.8 4 kg ; P = 0.001 ) , leg curl ( 5.3 0.4 kg compared with 14.4 1.5 kg ; P = 0.003 ) , and bench press ( 20.9 1.1 kg compared with 31.3 2.2 kg ; P = 0.008 ) . Neither women nor men showed changes in peak aerobic capacity after resistance training . No participant had significant changes in body weight , percentage of body fat , fat mass , or fat-free mass as measured by underwater weighing ( Table 1 ) . Analysis of regional body composition measured by dual-energy x-ray absorptiometry scanning showed an increased lean mass of the leg with weight training when compared with controls ( P = 0.02 ) ( Table 1 ) . This was due to an increase among women ( P 0.2 ) . Peak aerobic capacity was unaltered in both groups , regardless of sex . The primary outcome variable of interest was walking endurance time . After the resistance-training program , mean walking time until exhaustion for the resistance-training group increased by 38 % , from 25 4 minutes to 34 9 minutes . In contrast , no change was seen in the control group ( 20 5 minutes to 19 10 minutes ; P = 0.005 for comparison between groups ) . The increase in endurance time was due primarily to increases seen among men ( P 0.2 ) . Mean exercise intensity , measured at 10 minutes of the endurance protocol at baseline , was 82 % of peak aerobic capacity in both the training group and the control group ( P > 0.2 between groups ) . Before the study intervention , none of the 24 participants completed the full 45-minute endurance protocol . After conditioning , 3 of the 12 participants who received resistance training and 1 of 12 controls completed the entire protocol . After conditioning , mean scores for perceived exertion for all submaximal data points from 10 minutes until the end of the walking endurance protocol ( not including the exhaustion point ) were lower in the resistance-training group than in the control group ( P = 0.03 ) ( Figure 1 ) . Mean submaximal heart rate and systolic blood pressure measures were lower after conditioning ; however , when groups were compared by repeated-measure analysis of variance , differences between groups were not significant ( Figure 1 ) . Submaximal or peak exercise oxygen consumption did not change during the endurance testing . Figure 1 . Conditioning data in the resistance-training group . For all 24 participants , significant relations were seen between change in walking endurance and change in strength measures for leg extension ( r = 0.48 [ 95 % CI , 0.10 to 0.74 ] ; P = 0.02 ) and leg flexion ( r = 0.46 [ CI , 0.07 to 0.73 ] ; P = 0.03 ) . Baseline peak aerobic capacity ( r = 0.10 [ CI , 0.48 to 0.3 ] ; P > 0.2 ) and baseline endurance time ( r = 0.41 [ CI , 0.22 to 0.73 ] ; P = 0.13 ) were not significantly related to change in endurance capacity in the resistance-training group of 12 participants . Discussion We show that healthy , community-dwelling elders can improve walking endurance and leg strength by participating in a resistance-training program . This finding is relevant to persons at risk for disability because walking endurance and leg strength are important components of physical functioning [ 3 ] . Resistance training improves walking endurance in at", "OBJECTIVE To determine the effectiveness of progressive resistance strengthening exercises to improve gross motor function and walking in patients receiving intensive rehabilitation after stroke . DESIGN R and omized controlled trial . SETTING Five inpatient rehabilitation programs affiliated with teaching hospitals . PARTICIPANTS Inclusion criteria included less than 6 months poststroke and recovery of the leg stages 3 to 5 on the Chedoke-McMaster Stroke Assessment ( CMSA ) . INTERVENTIONS Both groups received conventional physical therapy programs . In addition , the experimental group performed 9 lower-extremity progressive resistance exercises 3 times a week for the duration of their stay , whereas the control group did the same exercises and for the same duration but without resistance . MAIN OUTCOME MEASURES The Disability Inventory of the CMSA and the 2-minute walk test ( 2MWT ) at baseline , 4 weeks , discharge , and 6 months after discharge . RESULTS Over the length of stay , the rate of change in the Disability Inventory was.27 points per day in the experimental group and .29 points per day in the control group ; the between-group difference was -.02 points per day ( 95 % confidence interval [ CI ] , -.10 to.06 ; P=.62 ) . At discharge , the rate of change in the 2MWT was -.01 m in the experimental group and .15 m in the control group ; the between-group difference was -.16 m ( 95 % CI , -.37 to.05 ; P=.14 ) . CONCLUSIONS Progressive resistance strengthening exercises as applied in our study were not effective when compared with the same exercises given without resistance", "OBJECTIVE To investigate the effects of a dynamic , intensive exercise regimen on pain , disease activity , and physical functioning in active rheumatoid arthritis ( RA ) . METHODS 64 patients with RA with a mean age of 60 ( 13 ) years and mean disease duration of 8 ( 8) years , admitted to hospital because of active disease , were r and omly assigned to an intensive exercise programme or to a conservative exercise programme during their period in hospital with a mean length of 30 ( 14 ) days . The intensive exercise programme consisted of knee and shoulder dynamic and isometric muscle strengthening exercises against resistance five times a week and conditioning bicycle training three times a week and was supplemental to the conservative exercise programme of range of motion and isometric exercises . Indices of disease activity , pain , muscle strength , and functional ability were assessed at 0 , 3 , 6 , 12 , and 24 weeks by a blinded observer . RESULTS The medical treatment during the study was the same in both groups . Both groups improved in measures of disease activity , differences between groups were not statistically significant . The mean improvement in disease activity score at 24 weeks in the intensive and conservative exercise group was −1.4 ( 1.5 ) and −0.7 ( 1.4 ) , respectively . Measures of physical functioning improved significantly for patients in the intensive exercise group , and differences between groups were statistically significant for measures of muscle strength . CONCLUSION A short term intensive exercise programme in active RA is more effective in improving muscle strength than a conservative exercise programme and does not have deleterious effects on disease activity", "We sought to determine whether creatine monohydrate ( CrM ) supplementation would enhance the increases in strength and fat-free mass that develop during resistance exercise training in older adults . Twenty-eight healthy men and women over the age of 65 years participated in a whole-body resistance exercise program 3 days per week for 14 weeks . The study participants were r and omly allocated , in a double-blind fashion , to receive either CrM ( 5 g/d + 2 g of dextrose ; n = 14 ) or placebo ( 7 g of dextrose ; n = 14 ) . The primary outcome measurements included the following : total body mass , fat-free mass , one-repetition maximum strength for each body part , isometric knee extension , h and grip , and dorsiflexion strength , chair st and performance , 30-m walk test , 14-stair climb performance , muscle fiber type and area , and intramuscular total creatine . Fourteen weeks of resistance exercise training result ed in significant increases in all measurements of strength and functional tasks and muscle fiber area for both groups ( p fat-free mass and total body mass , as compared with placebo ( p isometric knee extension strength in men and women , as compared with placebo ( p isometric dorsiflexion strength ( p intramuscular total creatine in the CrM group ( p side effects of treatment or exercise training . This study confirms that supervised heavy resistance exercise training can safely increase muscle strength and functional capacity in older adults . The addition of CrM supplementation to the exercise stimulus enhanced the increase in total and fat-free mass , and gains in several indices of isometric muscle strength", "BACKGROUND AND PURPOSE The majority of patients after a hip fracture do not return to prefracture functional status . Depression has been shown to affect recovery . Although exercise can reduce impairments , access issues limit elderly people from participating in facility-based programs . The primary purpose of this study was to determine the effects and feasibility of a home exercise program of moderate- or high-intensity exercise . A secondary purpose was to explore the relationship of depression and physical recovery . SUBJECTS Thirty-three elderly people ( 24 women , 9 men ; mean = 78.6 years of age , SD = 6.8 , range = 64 - 89 ) who had completed a regimen of physical therapy following hip fracture participated in the study . Subjects were r and omly assigned to a resistance training group , an aerobic training group , or a control group . METHODS Subjects were tested before and upon completion of the exercise trial . Isometric lower-extremity force , 6-minute-walk distance , free gait speed , mental status , and physical function were measured . Each exercise session was supervised by a physical therapist , and subjects received 20 visits over 12 weeks . The control group received biweekly mailings . The resistance training group performed 3 sets of 8 repetitions at the 8-repetition maximum intensity using a portable progressive resistance exercise machine . The aerobic training group performed activities that increased heart rate 65 % to 75 % of their age-predicted maximum for 20 continuous minutes . RESULTS Resistance and aerobic training were performed without apparent adverse effects , and adherence was 98 % . All groups improved in distance walked , force produced , gait speed , and physical function . Isometric force improved to a greater extent in the intervention groups than in the control group . Depressive symptoms interacted with treatment group in explaining the outcomes of 6-minute-walk distance and gait speed . DISCUSSION AND CONCLUSION High-intensity exercise performed in the home is feasible for people with hip fracture . Larger sample sizes may be necessary to determine whether the exercise regimen is effective in reducing impairments and improving function . Depression may play a role in the level of improvement attained", "Background : Falls are among the leading causes of injuries and deaths . Results from a number of studies have suggested that a community-based exercise program may be effective in improving lower body strength , although some have shown only limited improvements . However , the impact of these programs on gait and balance are equivocal . Further , studies that have specifically targeted deconditioned elderly individuals , rather than individuals drawn from the general community , either showed limited or no improvements in gait and balance . Objective : This study examined the effectiveness of a community-based , short-term , low-intensity exercise intervention strategy on measures of mobility skills , gait and balance , and muscle strength for a clinical ly targeted group of elderly individuals at high risk of falls . Methods : 245 men and women aged 60 years or older were r and omized into either an intervention or control group and received a baseline ( T1 ) assessment . Subjects in the intervention group received up to 24 sessions ( 45 min long ) of low-intensity st and ard exercise modalities tailored to the individual patient over an 8- to 10-week period . At the conclusion of the program , the participants in the intervention group were instructed to continue performing the exercises at home until 1 year after T1 . Measures of physical function and performance were collected for all subjects at three different points of study enrollment . Results : Of the subjects assessed at baseline , 138 ( 56 % ) also had a postintervention assessment ( T2 ) , 128 ( 52 % ) had a 6-month follow-up assessment ( T3 ) , and 105 subjects had assessment s at all time points . Primary analyses were based on the 105 subjects who had assessment s at all time points . Intervention and control subjects did not differ in any of the physical function or performance measures at baseline . Between T1 and T2 , the intervention subjects showed significantly greater improvement than the control subjects on all outcomes , with improvements plateauing for most measures between T2 and T3 . Gait and balance scores continued to improve throughout the study period for both groups of subjects . Conclusions : This easily implemented , low-intensity exercise program may lead to improvements in physical functioning that are retained over the long term and effectively targets a clinical ly defined population of deconditioned elders at high risk of falling and sustaining serious injury", "Where strength training has been used in conjunction with functional-task training in older people , not only have there been improvements in leg strength but also improved function has been measured ( e.g. , Skelton & McLaughlin , 1996 ) . Many studies use participants from care homes rather than community dwellers . We investigated changes in leg power , balance , and functional mobility in community-dwelling sedentary men and women over 70 years of age ( n = 6 for training group [ TR ] ; n = 10 for control group [ CN ] ) . Progressive training took place over 24 weeks using seated and nonseated exercise . For TR , leg power increased 40 % , from 108 + /- 40 to 141 + /- 53 W ( p dynamic balance increased 48 % , from 22.3 + /- 7.9 to 33.1 + /- 6.1 cm ( p functional reach ) ; and functional mobility increased 12 % , from 7.46 + /- 1.32 to 6.54 + /- 1.41 s ( p timed walk ) . CN showed no significant change . In conclusion , a community-based exercise program led to large improvements in leg-extensor power , dynamic balance , and functional mobility", "OBJECTIVE To examine the effects of a 3-month low-intensity exercise program on physical frailty . DESIGN R and omized clinical trial . SETTING Regional tertiary-care hospital and academic medical center with an outpatient rehabilitation fitness center . PARTICIPANTS Eighty-four physically frail older adults ( mean age , 83 + /- 4 yrs ) . INTERVENTION Three-month low-intensity supervised exercise ( n = 48 ) versus unsupervised home-based flexibility activities ( n = 36 ) . MAIN OUTCOME MEASURES Physical performance test , measures of balance , strength , flexibility , coordination , speed of reaction , peripheral sensation . RESULTS Significant improvement was made by the exercise group on our primary indicator of frailty , a physical performance test ( PPT ) ( 29 + /- 4 vs 31 + /- 4 out of a possible 36 points ) , as well as many of the risk factors previously identified as contributors to frailty ; eg , reductions in flexibility , strength , gait speed , and poor balance . Although the home exercise control group showed increases in range of motion , the improvements in flexibility did not translate into improvements in physical performance capacity as assessed by the PPT . CONCLUSIONS Our results suggest that physical frailty is modifiable with a program of modest activities that can be performed by virtually all older adults . They also indicate that exercise programs consisting primarily of flexibility activities are not likely to reverse or attenuate physical frailty . Although results suggest that frailty is modifiable , it is not likely to be eliminated with exercise , and efforts should be directed toward preventing the condition", "OBJECTIVES The objectives of this study were to determine the effects of a strength-training program on walking speed and relative muscular stress , as measured by normalized integrated electromyographic ( nIEMG ) activity , while carrying a box of groceries and st and ing from a chair . DESIGN Prospect i ve intervention study . SETTING Volunteer subjects from the community of Birmingham , Alabama . PARTICIPANTS Fourteen healthy women aged 60 to 77 years . INTERVENTION Sixteen weeks of total body strength conditioning . MEASUREMENTS Before and after 16 weeks of strength conditioning , the following variables were evaluated for all subjects : ( 1 ) strength , six isotonic tests and two isometric tests ; ( 2 ) walking velocity ; ( 3 ) nIEMG of the biceps while carrying a box of groceries ; and ( 4 ) nIEMG of the rectus femoris while st and ing from a chair . MAIN RESULTS After the strength training program , subjects ' isotonic strength increased significantly , an average of 52 % on the isotonic tests and 31 % on the isometric tests . Walking velocity also increased significantly ( 18 % ) . nIEMG of the biceps decreased 36 % while carrying a box of groceries . Rectus femoris nIEMG decreased 40 % while st and ing and 47 % while sitting . CONCLUSIONS After strength conditioning , healthy older women showed not only substantially increased strength but also improvements in walking velocity and the ability to carry out daily tasks such as rising from a chair and carrying a box of groceries", "PURPOSE This r and omized controlled study assessed whether adding a program of high-intensity strength training ( 80 % of maximum ) to an outpatient cardiac rehabilitation program would be a safe and effective means of improving muscle strength and body composition . METHODS Thirty-eight cardiac patient volunteers ( 29 men and 9 women ) were r and omized to either high-intensity strength training or flexibility training added concurrently to a 12-week outpatient cardiac rehabilitation aerobic exercise program . Muscle strength , local muscle endurance , joint flexibility , maximum treadmill tolerance time , and body composition were measured before and after completion of the training . RESULTS The strength-trained patients ( n = 18 ) had greater increases in mean strength ( 90 + /- 19 % versus 9 + /- 4 % , P local muscle endurance ( 20 versus 6 times , P mean perceived exertion for lifting the initial one repetition maximum load ( 11 + /- 1 versus 15 + /- 1 , P body fat ( 2.8 + /- 2.0 versus 1.3 + /- 2.0 kg , P gain more lean tissue ( 1.5 + /- 2.3 versus 0.5 + /- 1.2 kg , P improvements in treadmill time ( 2.3 + /- 1.3 versus 1.2 + /- 1.0 minute , P joint flexibility were similar for each group . None of the subjects had evidence of cardiac ischemia or arrhythmia during the training sessions . CONCLUSIONS Medically supervised high-intensity strength training is well tolerated when added to the aerobic training of cardiac rehabilitation programs and allows patients to aggressively gain the strength and endurance they will need to complete daily living tasks at lower perceived efforts . Strength training also reduces cardiac risk factors by improving body composition and maximum treadmill exercise time", "Patients who are on hemodialysis commonly experience muscle wasting and weakness , which have a negative effect on physical functioning and quality of life . The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis . A r and omized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California , San Francisco-affiliated dialysis units . Interventions included double-blinded weekly n and rolone decanoate ( 100 mg for women ; 200 mg for men ) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights . Primary outcomes included change in lean body mass ( LBM ) measured by dual-energy x-ray absorptiometry , quadriceps muscle cross-sectional area measured by magnetic resonance imaging , and knee extensor muscle strength . Secondary outcomes included changes in physical performance , self-reported physical functioning , and physical activity . Sixty-eight patients completed the study . Patients who received n and rolone decanoate increased their LBM by 3.1 + /- 2.2 kg ( P LBM . Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise ( P = 0.01 ) and to n and rolone ( P strength in a training-specific fashion , and exercise was associated with an improvement in self-reported physical functioning ( P = 0.04 compared with nonexercising groups ) . N and rolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis . Further studies are needed to determine whether these interventions improve survival", "The purpose of this study was to examine the effects of a 14-week resistance training program on the anile strength training intensity , postural control , and gait velocity of older adults . Forty-two older adults ( mean age = 72 ) , 21 in the resistance and control groups , completed the 14-week project . The resistance training group participated in 14 weeks of resistance training three times per week using elastic b and s ( Therab and ) for resistance . Isokinetic ankle strength , training intensity , postural stability , and gait velocity were measured prior to and following the 14-week intervention . Following the training , the resistance group exhibited improved ankle dorsiflexion , training resistances , and gait velocity , but showed no change in plantar flexion or postural control . The control group also exhibited improvements in dorsiflexion , but these gains were approximately one-half of the gains observed in the resistance training group . Finally , when adjusted for baseline differences , subjects in the resistance training group demonstrated no changes in the dependent measures over the control group", "OBJECTIVE To determine the effect of a home exercise program on strength , postural control , and mobility following hip fracture . DESIGN R and omized controlled trial of 1 month 's duration . SETTING Daily exercise carried out within the subjects ' home environments . PARTICIPANTS Forty-two people 64 to 94 years of age , 35 of whom were living independently in the community and 7 of whom were residing in institutional care . Subjects were recruited on average 7 months after a fall-related hip fracture and r and omly allocated to either the intervention or the control group ( n = 21 each ) . The groups were well matched in terms of medical conditions , medication use , disability , and activity levels . INTERVENTION A \" home-based \" program of weight-bearing exercise established at a visit by a physiotherapist . MAIN OUTCOME MEASURES Quadriceps strength , postural sway , functional reach , weight-bearing ability , walking velocity , and self-rated fall risk . The subjects undertook these assessment s at the beginning and end of the trial . RESULTS At pretest , exercisers and controls performed similarly in all tests . At the end of the trial , the intervention group showed significantly greater quadriceps strength in the affected ( hip-fractured ) leg and increased walking velocity . The intervention subjects also improved their weight-bearing ability and reported reduced subjective falls risk . In contrast , there were no significant improvements in any of the test measures in the controls . Within the intervention group , improvements in quadriceps strength were significantly associated with improved performances in the weight-bearing test measures and with increased walking velocity . CONCLUSIONS This exercise program improved strength and mobility following hip fracture . Further research is needed to ascertain whether the extent of this improvement in these fall risk factors is sufficient to prevent falls", "BACKGROUND Strength loss is strongly associated with functional decline and is reversible with exercise . The effect of increased strength on function has not been clearly established . The purpose of this study was to determine whether strength gain is associated with improvement in physical performance and disability . METHODS One hundred functionally impaired community-dwelling men and women ( 77.6 + /- 7.6 yrs ) were tested at baseline and outcome for lower extremity strength , physical performance , and disability . After r and om group assignment , exercise participants received strengthening exercises in their homes three times a week for 10 weeks while control subjects continued their normal activities . Using multiple regression techniques , the relationship between strength gain and improvement in physical performance and disability was assessed , controlling for age , depression , and baseline strength . RESULTS A significant impact of strength gain on mobility skills ( p = .0009 ) was found . The impact of strength gain on chair rise performance was significant in participants who were more impaired ( p = .04 ) . Strength gain was associated with gain in gait speed ( p = .02 ) and in falls efficacy ( p = .05 ) , but not with other balance , endurance , or disability measures . CONCLUSIONS Lower extremity strength gain is associated with gains in chair rise performance , gait speed , and in mobility tasks such as gait , transfers , stooping , and stair climbing , but not with improved endurance , balance , or disability . Strength gain is also associated with improvement in confidence in mobility . Factors that may influence the ability of strength gain to affect function are initial level of frailty and specificity of exercise . These results support the idea that strength training is an intervention that can potentially improve physical health status in many frail elders", "Skeletal muscle wasting is common and insidious in patients who receive maintenance hemodialysis treatment for the management of ESRD . The objective of this study was to determine whether 12 wk of high-intensity , progressive resistance training ( PRT ) administered during routine hemodialysis treatment could improve skeletal muscle quantity and quality versus usual care . Forty-nine patients ( 62.6 + /- 14.2 yr ; 0.3 to 16.7 yr on dialysis ) were recruited from the outpatient hemodialysis unit of the St. George Public Hospital ( Sydney , Australia ) . Patients were r and omized to PRT + usual care ( n = 24 ) or usual care control only ( n = 25 ) . The PRT group performed two sets of 10 exercises at a high intensity ( 15 to 17/20 on the Borg Scale ) using free weights , three times per week for 12 wk during routine hemodialysis treatment . Primary outcomes included thigh muscle quantity ( cross-sectional area [ CSA ] ) and quality ( intramuscular lipid content via attenuation ) evaluated by computed tomography scan . Secondary outcomes included muscle strength , exercise capacity , body circumference measures , proinflammatory cytokine C-reactive protein , and quality of life . There was no statistically significant difference in muscle CSA change between groups . However , there were statistically significant improvements in muscle attenuation , muscle strength , mid-thigh and mid-arm circumference , body weight , and C-reactive protein in the PRT group relative to the nonexercising control group . These findings suggest that patients with ESRD can improve skeletal muscle quality and derive other health-related adaptations solely by engaging in a 12-wk high-intensity PRT regimen during routine hemodialysis treatment sessions . Longer training duration s or more sensitive analysis techniques may be required to document alterations in muscle CSA", "To investigate the effects of cessation and subsequent resumption of training on muscle strength in elderly men , 11 men ( aged 65 - 77 years ) , just completing a 24-week r and omized controlled trial of recombinant human growth hormone ( rhGH ) and resistance exercise ( rhGH , n = 6 ; placebo , n = 5 ) , detrained for 12 weeks and subsequently retrained for 8 weeks . During the detraining and retraining phase , subjects did not receive rhGH . The resistance programme included three sets of eight repetitions at 75 % of one-repetition maximum ( 1-RM ) , three times per week , for 10 upper and lower body exercises . Dynamic muscle strength was assessed by the 1-RM method every 2 weeks for 44 weeks . Needle biopsies of vastus lateralis muscle were obtained from seven men . Muscle strength increased during initial training by 40.4 + /- 5.5 % ( mean + /- SEM ) , ranging from 26.0 + /- 5.0 to 83.9 + /- 15.6 % , depending on muscle group . Increased strength was accompanied by hypertrophy ( P strength gains , only 29.9 + /- 5.2 % was lost with detraining . However , type I and II fibre cross-sectional area reverted to pretraining values . After 8 weeks of retraining , muscle strength returned to trained values , but without a significant change in fibre morphology . The results indicate that elderly men lose some muscle strength following short-term detraining , but that only a brief period of retraining suffices to regain maximal strength . Reversal of fibre cross-sectional area with detraining , and only modest improvement with retraining , suggests that much of the retention in strength with detraining and reacquisition of lost strength with retraining reflects neural adaptation", "PURPOSE This study examined the effects of 24 wk of high intensity strength training or low intensity walking on lumbar bone mineral density ( BMD ) , muscular strength , and calcium turnover in Australian women either taking hormone replacement therapy ( HRT ) or not taking HRT . METHODS A subject pool of 64 women between 45 - 65 yr and r and omly allocated into weights ( N = 21 ) , walking ( N = 20 ) , weightsHRT ( N = 14 ) , and walkingHRT ( N = 9 ) groups completed this study . All subjects trained twice weekly in either a 50-min walking or weight-training program ( 60 - 90 % IRM ) . Measurements included maximal isometric knee strength , IRM bench press , IRM squat , isokinetic back strength , lumbar ( L2-L4 ) BMD , serum osteocalcin , and urinary deoxypyridinoline crosslinks ( Dpd ) . RESULTS No significant group differences in BMD were evident at the completion of training . However , a significant ( P BMD decreased 1.3 % below baseline testing . Osteocalcin levels increased significantly ( P Maximal bench press and squat strength improved significantly ( P isokinetic back strength ( 22.2 % ) . CONCLUSION It was concluded that short-term high intensity resistance training provides an effective means for increasing muscular strength in women between 45 and 65 yr . The training effects on lumbar BMD were not apparent in the present study", "Progressive resistance training has positive effects on the health of elderly people , however exercise programs for seniors frequently focus on other forms of exercise . This study is a r and omised trial with a blinded assessor comparing a community based progressive resistance training program ( n = 20 ) with a flexibility program ( n = 20 ) , both one hour twice weekly for 10 weeks . Outcomes were strength , gait , balance and quality of life . Progressive resistance training had a greater effect than flexibility training on right sided quadriceps strength ( mean difference between groups = 7.7 % ; 95 % CI 3.6 - 11.8 % , p left sided quadriceps strength ( mean difference = 9.9 % ; 95 % CI 5.6 - 14.2 % , p left sided biceps strength ( mean difference = 15.2 % ; 95 % CI 11.7 - 19.2 % , p functional reach ( mean difference = 11.7 % ; 95 % CI 7.1 - 16.3 % , p step test ( mean difference = 8.6 % ; 95 % CI 3.8 - 13.4 % , p SF36 quality of life measures . Results suggest progressive resistance training produces greater strength , gait and balance improvements in elderly people than a flexibility exercise program", "Knowledge of the effects of exercise on bone mass in postmenopausal women is limited and controversial . Animal studies have shown that the response of bone to bending strain is an alteration of bone geometry . We studied 250 postmenopausal women , aged 52 - 72 years , willing to participate in a 6-month exercise program . The first 125 started the program immediately and the remaining 125 served as controls . The training program included exercises design ed to maximize the stress on the wrist . One hundred and eighteen of the active group and 116 of the control group completed the study and were reassessed 6 months later . Bone mineral density ( BMD ) of the femoral neck , lumbar spine , ultradistal and proximal radius was measured by dual-energy X-ray absorptiometry ( DXA ) both before and at the end of the exercise program . The forearm was also evaluated by peripheral quantitative computed tomography , which measures the area , bone mineral content ( BMC ) , and volumetric density for both the cortical and the trabecular component . The results showed that the DXA measurements at the femoral neck , lumbar spine , ultradistal and proximal radius were similar between the two groups . No significant difference was detected after the exercise program at the proximal radius . At the ultradistal radius , the cross-sectional area of cortical bone rose by 2.8 + /- 15.0 % ( SD , p apposition and corticalization of the trabecular tissue . The volumetric density of cortical bone rose by 2 . 2 + /- 15.8 % ( p trabecular bone decreased by 2.6 + /- 10.7 % ( p bone volume and density in the exercise group were associated with marked increase in cortical BMC ( 3.1 + /- 10.7 % , p trabecular BMC ( -3.4 + /- 14.2 % , p bone mass . However , it appears that some exercises may reshape the bone segment under stress by increasing both the cross-sectional area and the density of the cortical component . These structural changes are theoretically associated with increases in the bending strength", "This study was design ed to determine whether an 8-week isokinetic muscle-strength-training program improved the functional health status of patients with osteoarthritis of the knee joint . Twenty volunteers with osteoarthritis of the knee joint were r and omly assigned to either an experimental ( n=10 ) or control ( n=10 ) group . The experimental group completed six sets of five maximal contractions three times per week for 8 weeks on a Cybex II dynamometer at 90 degrees per second . Both groups were pre- and posttest for extension and flexion strength of the right and left legs , the 50-foot walk time , range of motion at the knee joint , the Osteoarthritis Screening Index ( OASI ) , and the Arthritis Impact Measurement Scale ( AIMS ) . There was a significant decrease in pain and stiffness , and a significant increase in mobility . There was also a significant decline in arthritis activity in the experimental group as measured by the OASI and AIMS . The experimental group significantly increased in all strength measures , while the control group increased in only right leg flexion and left leg extension across the training period", "This study investigated changes in elderly muscle joint angle-torque relation induced by resistance training . Older adults were assigned to either training ( n = 9 , age 74.3 + /- 3.5 years ; mean + /-s.d . ) or to control groups ( n = 9 , age 67.1 + /- 2 years ) . Leg-extension and leg-press exercises were performed three times per week for 14 weeks . Maximal isometric knee extension torque was measured across the knee joint angle range of movement . Vastus lateralis muscle architecture was examined in vivo using ultrasonography . The vastus lateralis muscle fascicle force was estimated from the measured joint torque , enabling construction of the fascicle length-force relation . Electromyographic ( EMG ) activity was measured from representative agonist and antagonist muscles . Training altered the angle-torque relation : ( a ) displacing it by 9 - 31 % towards higher torque values ( P fascicle length-force relation : ( a ) displacing it by 11 - 35 % towards higher force values ; and ( b ) shifting the optimal fascicle length from 83.7 + /- 8 mm ( corresponding force : 847.9 + /- 365.3 N ) before to 93.2 + /- 12.5 mm ( 939.3 + /- 347.8 N ; P upward displacement of the angle-torque relation was mainly due to a training-induced increase in agonist activation , whilst the shift in the optimal angle was associated with changes in muscle-tendon properties", "BACKGROUND Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people , the efficacy of interventions targeted specifically at these deficits has not been carefully studied . METHODS We conducted a r and omized , placebo-controlled trial comparing progressive resistance exercise training , multinutrient supplementation , both interventions , and neither in 100 frail nursing home residents over a 10-week period . RESULTS The mean ( + /- SE ) age of the 63 women and 37 men enrolled in the study was 87.1 + /- 0.6 years ( range , 72 to 98 ) ; 94 percent of the subjects completed the study . Muscle strength increased by 113 + /- 8 percent in the subjects who underwent exercise training , as compared with 3 + /- 9 percent in the nonexercising subjects ( P Gait velocity increased by 11.8 + /- 3.8 percent in the exercisers but declined by 1.0 + /- 3.8 percent in the nonexercisers ( P = 0.02 ) . Stair-climbing power also improved in the exercisers as compared with the nonexercisers ( by 28.4 + /- 6.6 percent vs. 3.6 + /- 6.7 percent , P = 0.01 ) , as did the level of spontaneous physical activity . Cross-sectional thigh-muscle area increased by 2.7 + /- 1.8 percent in the exercisers but declined by 1.8 + /- 2.0 percent in the nonexercisers ( P = 0.11 ) . The nutritional supplement had no effect on any primary outcome measure . Total energy intake was significantly increased only in the exercising subjects who also received nutritional supplementation . CONCLUSIONS High-intensity resistance exercise training is a feasible and effective means of counteracting muscle weakness and physical frailty in very elderly people . In contrast , multi-nutrient supplementation without concomitant exercise does not reduce muscle weakness or physical frailty", "Objective : To examine the effectiveness of task-oriented progressive resistance strength training on lower extremity strength and functional performance in chronic stroke subjects . Design : Single-blind , r and omized controlled trial . Setting : Medical centre and district hospital . Subjects : Forty-eight subjects at least one year post stroke . Interventions : Participants r and omly allocated to two groups , control ( n-/24 ) and experimental ( n-/24 ) . Subjects in the control group did not receive any rehabilitation training . Subjects in the experimental group were put on a four-week task-oriented progressive resistance strength training . Main measures : Lower extremity muscle strength , gait velocity , cadence , stride length , six-minute walk test , step test , and timed up and go test . Results : Muscle strength significantly improved in the experimental group for strong side muscle groups ( ranged from 23.9 % to 36.5 % ) and paretic side muscle groups ( ranged from 10.1 % to 77.9 % ) . In the control group muscle strength changes ranged from 6.7 % gain to 11.2 % decline . The experimental group showed significant improvement in all selected measures of functional performance except for the step test . In the control group , the number of repetitions of the step test significantly decreased ( -20.3 % ) with no change in other functional tests . There was a significant difference between groups for muscle strength and all functional measures . The strength gain was significantly associated with gain in the functional tests . Conclusions : The task-oriented progressive resistance strength training programme could improve lower extremity muscle strength in individuals with chronic stroke and could carry over into improvement in functional abilities", "Background : While the fear of falling is a common psychological consequence of falling , older adults who have not fallen also frequently report this fear . Fear of falling can lead to activity restriction that is self-imposed rather than due to actual physical impairments . Evidence suggests that exercise can significantly improve balance confidence , as measured by falls-related self-efficacy scales . However , there are no prospect i ve reports that correlate change in balance confidence with changes in fall risk and physical abilities as induced by participating in a group-based exercise program . Objective : The primary purpose of this prospect i ve study was to examine the relationship between the change in balance confidence and the changes in fall risk and physical abilities in older women with confirmed low bone mass after 13 weeks of exercise participation . The secondary purpose of this study was to examine the relationship between the change in balance confidence and the change in physical activity level . Methods : The sample comprised 98 women aged 75–85 years with low bone mass . Participants were r and omly assigned to one of three groups : resistance training ( n = 32 ) , agility training ( n = 34 ) , and stretching ( sham ) exercises ( n = 32 ) . The 50-min exercise classes for each study arm were held twice weekly at a local YMCA community centre . Results : Both resistance training and agility training significantly improved balance confidence by 6 % from baseline after 13 weeks . However , the change in balance confidence was only weakly correlated with improved general physical function and not significantly correlated with the changes in fall risk score , postural stability , gait speed , or physical activity level . As well , we observed balance confidence enhancement in the presence of increased fall risk or deterioration in physical abilities . Conclusions : Two different types of exercise training improved balance confidence in older women with low bone mass . This change in balance confidence was significantly correlated with change in general physical function . Because of the observation of discordance between balance confidence change and changes in fall risk and physical abilities , those who design group-based exercise programs for community-dwelling older adults may wish to consider including an education component on factors that influence fear of falling . Objective changes in fall risk factors can not be assumed to mirror change in fear of falling and physical abilities in older adults in the short-term", "BACKGROUND Older people with somatic illnesses are at increased risk of depression . It is not known whether exercise alleviates depressive symptoms in frail , very old people recuperating from an acute illness . OBJECTIVE To determine the effects of a group-based exercise training program on mood . METHODS Sixty-eight women ( mean age 83.0 , SD 3.9 years ) who were hospitalized due to an acute illness , and were mobility impaired at admission , were r and omized into group-based 10-week strength training intervention ( N=34 ) and home exercise control ( N=34 ) groups . Twenty-four women in the training and 28 in the control group completed the follow-up . Measures of mood state with the Zung Self-Rating Depression Scale ( ZSDS ) were performed before and after the training intervention , and follow-up data was collected 3 and 9 months after the end of the intervention . RESULTS After the intervention , there was a significant improvement in mood in the intervention group compared to the home exercise control group : -3.1 ( SD 9.0 ) points vs + 1.3 ( SD 7.6 ) points ( p=0.048 ) and the positive effect was still apparent three months after the intervention ceased : -2.6 ( SD 7.7 ) points vs + 3.5 ( SD 9.7 ) points ( p=0.015 ) . Improvement of mood state at the first follow-up measurement was associated with the improvement in lower limb isometric muscle strength . CONCLUSIONS Group-based exercise program organized in the context of a Finnish health care organization improved mood in frail older women recuperating from an acute illness", "We examined the effects of 42 weeks of progressive weight-lifting training on dynamic muscle strength , peak power output in cycle ergometry , symptom limited endurance during progressive treadmill walking and stair climbing , knee extensor cross-sectional areas , and bone mineral density and content in healthy males and females aged 60 - 80 years , currently enrolled in a 2-year resistance training program . Subjects were r and omized into either exercise ( EX ) or control ( CON ) groups ( 60 - 70 years : 38 males and 36 females ; 70 - 80 years : 25 males and 43 females ) . EX trained several muscle groups twice per week for 42 weeks at intensities ranging from 50 - 80 % of the load that they could lift once only ( 1 RM ) ; CON did usual daily activities . After the 10 months there was no change in 1 RM strength in CON , but significant gains ( mean increases up to 65 % ) in EX ( no independent age or gender effects ) ; 30 % and 47 % of the increase in 1 RM had occurred by 6 and 12 weeks , respectively . In EX , the 7.1 % increase in peak cycling power output was significantly greater than in CON ( + 1.1 % ) . The 17.8 % improvement in symptom limited treadmill walking endurance was also greater than in CON ( + 3.4 % ) , but the difference between groups during stair climbing was not significant ( EX + 57 % , CON + 33 % ) . The cross-sectional areas of the knee extensors increased significantly by 5.5 % in EX but were unchanged in CON . There were no changes in bone mineral density or content in either group . We conclude that long-term resistance training in older people is feasible and results in increases in dynamic muscle strength , muscle size , and functional capacity", "The aim of the present study was to evaluate the effects of a 16-week progressive high-intensity strength training ( HIST ) program on peripheral markers of bone turnover ( bone Gla protein , BGP ; bone alkaline phosphatase , B-AP ; N-terminal propeptide of type I procollagen , PINP ; C-terminal cross-linked telopeptide of type I collagen , ICTP ) in healthy , elderly men over 65 yr of age . Thirty healthy men ( aged 65–81 yr ) , performing light to moderate daily physical activity , were r and omly divided into two groups . Group 1 ( no.=16 ) followed a supervised 16-week progressive HIST program , while subjects of group 2 ( no.=14 ) , used as controls , were requested to maintain their habitual level of physical activity for 16 weeks . HIST program consisted of 6 different sets of exercise ( 2 involving the major muscle groups of the lower limb and 4 involving those of the upper limb ) . Three sessions/week , during which 10 repetitions of each exercise set were completed , were performed . Lower limb exercises shifted from 50 to 80 % of the one maximal repetition ( 1MR ) during the first month of the protocol and were thereafter maintained at an intensity of 80 % 1MR throughout the training . Upper limb exercises shifted from 40 to 65 % of 1MR with a similar pattern . All sessions were preceded by 15 min of cycloergometer exercise at 50 % of maximal oxygen uptake and by a warm-up of 15 repetitions at 20 % of 1MR of each exercise set . The HIST program did not significantly change BGP ( mean±SE , before : 15.6±1.2 μg/l vs after : 16.0±1.2 μg/l , NS ) and PINP levels ( before : 44.6±6.7 μg/l vs after : 43.1±6.0 μg/l , NS ) . On the contrary , serum B-AP significantly increased ( before : 50.2±6.1 IU/l vs after : 62.3±7.0 IU/l , p ( before : 4.0±0.3 μg/l vs after : 3.8±0.3 μg/l , p , a significant improvement in this ratio was found in all subjects of group 1 ( before : 12.9±1.3 IU/μg vs after : 17.3±1.5 IU/μg , p 2 . No significant changes of IGF-I levels were observed after the HIST program ( before : 94.9±9.4 μg/l vs after : 89.9±9.7 μg/l ) . No significant changes of BGP , PINP , B-AP , ICTP , B-APICTP ratio and IGF-I levels were observed in controls ( group 2 ) during the 16 weeks of observation . Although the positive effects of a progressive HIST program on B-AP levels and B-AP-ICTP ratio seem promising , the support of bone mass measurement and the determination of other bone markers are requested to better identify exercise protocol ( duration , intensity ) for elderly people", "PURPOSE The recommendations for exercise training and physical activity for older adults include cardiovascular and resistance training components ( CVT and RT , respectively ) . The purpose of the present investigation was to compare the fitness benefits of concurrent CVT and RT with those attained through an equivalent duration of CVT or RT alone . METHODS Thirty-six participants ( ages 60 - 84 ) were assigned to a control group or to one of three exercise treatment groups . The treatment groups exercised three times per week for 12 wk using RT ( N = 11 ) , CVT ( N = 10 ) , or CVT and RT ( BOTH , N = 9 ) . Pre- and post-training , participants performed a submaximal exercise test ( GXT ) , five repetition-maximum strength tests ( 5RM ) , and the AAHPERD functional fitness test for older adults . RESULTS All exercise treatment groups revealed lower resting heart rate and rate-pressure product ; lower exercise diastolic blood pressure and rating of perceived exertion ; increased GXT duration ; increased leg , back , and shoulder 5RM scores ; and improved AAHPERD flexibility , coordination , and cardiovascular endurance scores . The exercise treatment groups responded differently on the following : RT and BOTH enhanced arm and chest strength more than CVT ; and BOTH enhanced AAHPERD strength and agility scores more than CVT or RT . CONCLUSIONS Concurrent CVT and RT is as effective in eliciting improvements in cardiovascular fitness and 5RM performance as CVT or RT , respectively . Moreover , incorporating both CVT and RT in exercise programs for older adults may be more effective in optimizing aspects of functional fitness than programs that involve only one component", "OBJECTIVE To evaluate the effectiveness of three different training protocol s on physical function of older adults living in long-term care facilities . Emphasis was placed on feasibility in real-life situations . METHODS Subjects ( N=224 ) were r and omised to 6 months of twice weekly ( 1 ) resistance training ; ( 2 ) all-round functional-skills training ; ( 3 ) a combination of both ; or ( 4 ) a control program . Fitness and performance measures and self-reported disability were measured at baseline and after 24 weeks intervention . RESULTS Attendance to the strength training was 76 % , to the functional-skills training 70 % and to the combined training 73 % . In those who attended at least 75 % of all classes ( n=97 ) the functional-skills and combined training program improved several fitness and performance measures compared to the control group . CONCLUSION Twice weekly functional-skills training , or a combination of resistance and functional-skills training can improve several fitness and performance measures of institutionalised older people . PRACTICE IMPLICATION S An important finding from our study was that less than twice a week exercise training is not enough for functional improvement , while it proved difficult for the elderly subjects to exercise twice weekly . Education on the health benefits of regular exercise , and a larger availability of classes in long-term care facilities may improve attendance", "This study tested whether a 12-week dynamic resistance strength training program can change gait velocity and improve measures of balance among adults age 65 and older . Fifty-five community-dwelling adults ( mean age = 71.1 ) were r and omized into an exercise ( n = 25 ) or control ( n = 30 ) group . The exercisers were requested to complete three bouts of strength training per week for 12 weeks using elastic tubing . At posttest the exercisers demonstrated slower gait velocity , enhanced balance , and an improved ability to walk backward , although none of these posttest measures was significantly different from the control group", "A preliminary 10-wk . study was conducted to determine the effect a combined strength and cardiovascular exercise protocol had on both physiological and psychological change in 17 older ( M age = 66.8 yr . ) , formerly sedentary women . The protocol was associated with better adherence than typically found for new and returning exercisers . Significant improvements over 10 wk . were found on Body Mass Index , body fat , resting heart rate , and balance . Significant , positive changes in mean ratings were also found on Physical Self-concept , Total Mood Disturbance , Depression , and Fatigue ( small to moderate treatment effect sizes ) . Although no significant changes were found for rated Tension , Vigor , Anger , and Confusion , mean changes were in the desired direction and rated Tension showed a moderate effect size . The need for replication , including a control group and follow-up , plus continued research on exercise protocol s both well-tolerated and effective for older individuals and other specific groups , were discussed", "Twenty active elderly subjects ( mean age = 66.4 years , range 51 - 81 ) participated in a 12-week weight-training program to determine the possibility of increasing muscular strength and lean body weight . The training utilized variable resistance weight machines which trained the major muscle groups . The male subjects ( n = 11 ) experienced an average increase of 66.1 % ( SD = 19.39 , p total maximum weight lifted while the females ( n = 9 ) showed an average increase of 72.2 % ( SD = 33.44 , p Lean body weight , which was calculated by skinfold measurements for each group did increase , but was not statistically significant ( males p weight-training regimen can have on an elderly population", "Abstract .Falls are a common hazard in the elderly . Orthostatic hypotension ( OH ) is prevalent in older patients and contributes to the high incidence of falls . Our aim was to test whether a home-based resistance-training program ( HBRT ) using elastic resistance b and s could safely and effectively increase muscle strength and functional ability , and attenuate the orthostatic fall in blood pressure . Eight subjects ( > 60 yrs ) underwent orthostatic provocations ; muscle strength testing ( isometric and dynamic ) , and a functional test of gait and mobility ( Timed Up & Go ) , at baseline and following 8 weeks of training . Ten exercises were assigned and customized to each participant . At 8 weeks , significant increases occurred in dynamic strength in the chest press ( p = 0.017 ) , quadriceps extension ( p = 0.017 ) , and leg press ( p = 0.025 ) ; no significant differences occurred in isometric strength or in blood pressures . Functional mobility increased in 7 of 8 subjects . There were no falls during the investigation period . Conclusion A HBRT program using elastic resistance b and s effectively increases dynamic muscle strength in elderly individuals with OH . Although no changes occurred in orthostatic blood pressures , which could be attributed to the limited length of the program , this therapy may be recognized as a safe method to improve strength , functional ability , and promote physical activity – variables that can reduce the incidence of falls and enhance the quality of life in this population" ]	4118340c-06ff-11f0-808a-c43d1ab1c353
Several studies have suggested that aerobic physical activity is safe and beneficial for HIV-infected adults . However , there is information lacking regarding whether HIV-infected patients practice physical activity and to what extent . Therefore , the aim of this systematic review was to determine the prevalence of physical activity , sedentary lifestyle or lack of physical activity in non-experimental conditions performed by HIV-infected subjects . The electronic search was conducted using Medline and EMBASE bibliographic data bases and the platforms of Bireme , Ovid , Science Direct , High Wire and SCIELO from January 1990 to July 2011 . Original observational studies were included . Of the 2,838 articles found , 48 met the inclusion criteria . Following data extraction and after reading the manuscripts , 24 were selected for systematic review . Of the 24 studies , most were cross-sectional studies . The average quality score using the modified Newcastle-Ottawa scale was 2.8±1.5 . The diversity of methods used to assess physical activity precluded the calculated summary estimate of prevalence . The percentage of sedentary lifestyle was determined in 13 articles which conducted studies on HIV-infected individuals . The percentage of sedentary lifestyle or physical inactivity ranged from 19%to 73 % , with the level determined by different methods . In conclusion , there are few well- design ed studies with adequate sample size to represent the population of HIV-infected individuals . A pooled estimate could not be calculated due to the differences in physical activity measurements and definitions of physically active and non-active HIV-infected individuals	[ "HIV-infected individuals are frequently active , but guidelines for exercise in this population lack scientific support , since studies on the effects of exercise training on immunologic variables of HIV-1 positive individuals have shown conflicting results . Exercise capacity , immunologic markers ( CD4 , CD8 and CD4:CD8 ratio ) , anthropometric measurements , and depression scores were evaluated to compare the effects of two intensities of aerobic exercise on HIV-1 seropositive individuals . Twenty-one healthy subjects ( 14 men , 7 women ) , carriers of the HIV-1 virus ( CD4>200 cells x mm(-3 ) ) , and inactive for at least 6 months , completed a 12 week exercise training program ( 36 sessions of 1 h , 3 times per week ) , in a moderate intensity group ( 60+/-4 % of maximal heart rate ) or a high intensity group ( 84+/-4 % of maximal heart rate ) . Exercise capacity estimated by treadmill time was increased significantly in both moderate intensity ( 680+/-81 s before ; 750+/-151 s after ) and high intensity ( 651+/-122 s before ; 841+/-158 s after ) groups , but the high intensity group presented a significantly larger increment ( p immunologic variables , anthropometric measurements or depression scores . Thus , HIV-seropositive individuals that participate in moderate and high intensity exercise programs are able to increase their functional capacity without any detectable changes in immunologic variables , anthropometric measurements or depression scores", "We examined the effects of chronic exercise on fitness and immune status in Caucasian males ( 34.9 + /- 5.6 yr ) diagnosed by Western blot as seropositive for the HIV-1 virus . The exercise regimen involved 12 wk of 1 h sessions 3 d.wk : 20 min of cycle exercise at 60 - 80 % HRreserve was followed by 35 min of strength and flexibility training . After matching subjects on health status ( modified Walter Reed criteria ) , subjects ( N = 37 ) were r and omly assigned to exercise or a counseling control condition . Changes in strength , responses to the YMCA cycle test , and serum lymphocytes were tested by MANOVA in a condition ( exercise or counseling)-by-time ( pretest , posttest ) design with repeated measures on time . Results indicated significant ( P less than 0.001 ) group-by-time interactions for strength ( N.m ) ( chest press and leg extension ) and for HR ( beats.min-1 ) and total time ( TT ) on the cycle test at 150 W. Strength and TT increased and HR decreased in the exercise condition , while control subjects did not change . Total leukocyte , lymphocyte , CD4 + , and CD8 + cell counts , and the CD4+/CD8 + ratio were statistically unchanged for each condition . We conclude that HIV-1 + men , including those symptomatic for AIDS-related complex , can experience significant increases in neuromuscular strength and cardiorespiratory fitness without changes in lymphocyte phenotypes or clinical diagnosis when the exercise regimen is prescribed and monitored in accordance with ACSM guidelines for healthy adults", "OBJECTIVE People living with HIV infection are at increased risk for developing cardiovascular disease ( CVD ) . Safe and effective interventions for lowering CVD risk in HIV infection are high priorities . We conducted a prospect i ve , r and omized , controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors , virological or immunological status , or quality of life ( QOL ) in HIV-infected adults relative to st and ard of care treatment in a matched control group . METHODS Sixty HIV-infected adults with mild-moderate CVD risk were assigned to 20 weeks of supervised yoga practice or st and ard of care treatment . Baseline and week 20 measures were : 2-h oral glucose tolerance test with insulin monitoring , body composition , fasting serum lipid/lipoprotein profile , resting blood pressures , CD4 T-cell count and plasma HIV RNA , and the Medical Outcomes Study Short Form (SF)-36 health-related QOL inventory . RESULTS Resting systolic and diastolic blood pressures improved more ( P=0.04 ) in the yoga group ( -5 + /- 2 and -3 + /- 1 mmHg , respectively ) than in the st and ard of care group ( + 1 + /- 2 and + 2 + /- 2 mmHg , respectively ) . However , there was no greater reduction in body weight , fat mass or proatherogenic lipids , or improvements in glucose tolerance or overall QOL after yoga . Immune and virological status was not adversely affected . CONCLUSION Among traditional lifestyle modifications , yoga is a low-cost , simple to administer , nonpharmacological , popular behavioural intervention that can lower blood pressure in pre-hypertensive HIV-infected adults with mild-moderate CVD risk factors" ]	4118347a-06ff-11f0-808a-c43d1ab1c353
Objective To perform a systematic review of published literature for the factors reported to predict outcomes of enhanced recovery after surgery ( ERAS ) programmes following laparoscopic colorectal surgery . Background ERAS programmes and the use of laparoscopy have been widely adopted in colorectal surgery bringing short-term patient benefit . However , there is a minority of patients that do not benefit from these strategies and their identification is not well characterised . The factors that underpin outcomes from ERAS programmes for laparoscopic patients are not understood . Methods A systematic search of the MEDLINE , Embase and Cochrane data bases was conducted to identify suitable articles published between 2000 and 2015 . The search strategy captured terms for ERAS , colorectal resection , prediction and outcome measures . Results Thirty-four studies containing 10,861 laparoscopic resections were included . Thirty-one ( 91 % ) studies were confined to elective cases . Predictive analysis of outcome was most frequently based on length of stay ( LOS ) , morbidity and readmission which were the main outcome measures of 29 ( 85 % ) , 26 ( 76 % ) and 18 ( 53 % ) of the included studies , respectively . Forty-seven percentage of included studies investigated the impact of ERAS programme compliance on these outcomes . Reduced protocol compliance was the most frequently identified modifiable predictive factor for adverse LOS , morbidity and readmission . Conclusion Protocol compliance is the most frequently reported predictive factor for outcomes of ERAS programmes following laparoscopic colorectal resection . Reduced compliance increases LOS , morbidity and readmission to hospital . The impact of compliance with individual ERAS protocol elements is insufficiently studied , and the lack of a st and ardised framework for evaluating ERAS programmes makes it difficult to draw definite conclusions about which factors exert the greatest impact on outcome after laparoscopic colorectal resection	[ "Background Elderly patients often are regarded as high-risk for major abdominal surgery because of a lack of functional reserve and associated medical comorbidities . The goal of this study was to compare the cost of care and short-term outcomes of elderly and nonelderly patients undergoing laparoscopic colectomy . Our hypothesis was that elderly patients managed with laparoscopic colorectal surgery and an enhanced recovery protocol ( ERP ) can realize the same benefits of lower hospital length of stay ( LOS ) without increasing hospital costs or readmission rates . Methods Review of a prospect i ve data base identified all patients that underwent an elective laparoscopic colectomy from 2009 to 2012 . Patients were stratified into elderly ( ≥70 years old ) and nonelderly ( The main outcome measures were discharge disposition , hospital costs , hospital LOS , and 30-day readmission rates between the laparoscopic and open groups . Results A total of 302 nonelderly ( 66 % ) and 153 elderly ( 34 % ) patients were included in the analysis . The elderly cohort had significantly higher comorbidities than the nonelderly group . There were no mortalities . Operative variables ( procedure time , blood loss , and intraoperative complications ) were similar . At discharge , significantly more elderly patients required temporary nursing or home care . There were no significant differences in short-term outcomes of LOS , 30-day readmission rates , or costs for the episode of care between the two groups . Conclusions Combining laparoscopic colectomy with an ERP is cost-effective and results in similar short-term outcomes for the elderly and nonelderly patients . Despite higher comorbidities , elderly patients realized the same benefits of shorter LOS with similar hospital costs and readmission rates", "BACKGROUND Perioperative treatment of patients with colorectal cancer according to the Enhanced Recovery After Surgery ( ERAS ) protocol has proven to reduce complications and duration of stay . However , strict adherence remains a challenge and the benefits may decrease with lower adherence . In this study , we report on 8 years of adherence to the ERAS protocol and its effect on postoperative outcome in patients with colon cancer . METHODS In 2006 , the ERAS protocol was introduced for treatment of colon cancer patients in the Medical Center Alkmaar , a large teaching hospital . Patients scheduled for elective colon cancer resection were included in this study . Adherence to ERAS items was monitored and along with clinical data prospect ively gathered in a data base . In 2011 , several measures to improve adherence were implemented . RESULTS In total , 816 patients were included . Mean adherence rate was 73 % in 2006 and 2007 , 66 % in 2008 and 2009 , 63 % in 2010 and 2011 , and 82 % in 2012 and 2013 . There was a shorter duration of stay in the years with high adherence ( 5.7 days ) compared with the years with low adherence ( 7.3 days ; P shorter duration of stay were no nasogastric tube , early mobilization , early oral nutrition , early removal of epidural , early removal of catheter , and nonopioid oral analgesia . CONCLUSION It is possible to improve adherence to the ERAS protocol and related outcomes with specific measures . Adherence to the ERAS protocol was related inversely to duration of stay . Only postoperative items of the ERAS protocol were predictive for a shorter duration of stay . Keeping adherence optimal remains an ongoing challenge that requires repeated training and dedicated personnel", "BACKGROUND Studies have shown the value of using fast-track postoperative recovery . St and ard procedures ( non-fast-track strategies ) remain in common use for perioperative care . Few prospect i ve reports exist on the outcome of fast-tracking in Central Europe . The aim of our study was to assess the effect and safety of our own fast-track protocol with regard to the postoperative period after open bowel resection . PATIENTS AND METHODS One hundred and five patients with ASA score I-II scheduled for open intestinal resection in the period April 2005-December 2007 were r and omly selected for the fast-track group ( FT ) and non-fast-track group ( non-FT ) . A design ed protocol was used in the FT group with the emphasis on an interdisciplinary approach . The control group ( non-FT ) was treated by st and ard established procedures . Postoperative pain , rehabilitation , gastrointestinal functions , postoperative complications , and post-op length of stay were recorded . RESULTS Of 105 patients , 103 were statistically analyzed . Patients in the FT group ( n=51 ) and non-FT group ( n=52 ) did not differ in age , surgical diagnosis , or procedure . The fast-track procedure led to significantly better control of postoperative pain and faster restoration of GI functions ( bowel movement after 1.3 days vs. 3.1 , p Food tolerance was significantly better in the FT group and rehabilitation was also faster . Hospital stay was shorter in the FT group - median seven days ( 95 % CI 7.0 - 7.7 ) versus ten days ( 95 % CI 9.5 - 11.3 ) in non-FT ( p Postoperative complications within 30 postoperative days were also significantly lower in the FT group ( 21.6 vs. 48.1 % , p=0.003 ) . There were no deaths and no patients were readmitted within 30 days . CONCLUSIONS Following the FT protocol helped to reduce frequency of postoperative complications and reduced hospital stay . We conclude that the FT strategy is safe and effective in improving postoperative outcomes", "OBJECTIVES To study the impact of different adherence levels to the enhanced recovery after surgery ( ERAS ) protocol and the effect of various ERAS elements on outcomes following major surgery . DESIGN Single-center prospect i ve cohort study before and after reinforcement of an ERAS protocol . Comparisons were made both between and across periods using multivariate logistic regression . All clinical data ( 114 variables ) were prospect ively recorded . SETTING Ersta Hospital , Stockholm , Sweden . PATIENTS Nine hundred fifty-three consecutive patients with colorectal cancer : 464 patients treated in 2002 to 2004 and 489 in 2005 to 2007 . MAIN OUTCOME MEASURES The association between improved adherence to the ERAS protocol and the incidence of postoperative symptoms , complications , and length of stay following major colorectal cancer surgery was analyzed . RESULTS Following an overall increase in preoperative and perioperative adherence to the ERAS protocol from 43.3 % in 2002 to 2004 to 70.6 % in 2005 to 2007 , both postoperative complications ( odds ratio , 0.73 ; 95 % confidence interval , 0.55 - 0.98 ) and symptoms ( odds ratio , 0.53 ; 95 % confidence interval , 0.40 - 0.70 ) declined significantly . Restriction of intravenous fluid and use of a preoperative carbohydrate drink were major independent predictors . Across periods , the proportion of adverse postoperative outcomes ( 30-day morbidity , symptoms , and readmissions ) was significantly reduced with increasing adherence to the ERAS protocol ( > 70 % , > 80 % , and > 90 % ) compared with low ERAS adherence ( multimodal ERAS protocol is significantly associated with improved clinical outcomes following major colorectal cancer surgery , indicating a dose-response relationship", "BACKGROUND This study was undertaken to determine the impact of an intrathecal mixture of bupivacaine and morphine , when compared with systemic morphine , on the quality of postoperative analgesia and other outcomes in the context of the enhanced recovery after surgery ( ERAS ) programme for laparoscopic colonic resection . METHODS Fifty patients undergoing general anaesthesia were r and omly allocated to receive either a spinal mixture of bupivacaine and morphine followed by oral oxycodone ( spinal group ) or patient-controlled analgesia ( PCA group ) . The primary outcome was consumption of opioids during the first three postoperative days . Secondary outcomes were pain scores , return of bowel function and dietary intake , readiness to hospital discharge , and length of hospital stay . RESULTS Postoperative opioid consumption in the spinal group was significantly less over the first three postoperative days ( P quality of analgesia at rest in the first 24 h was better in the spinal group ( P Excessive sedation and respiratory depression were reported in two elderly patients with spinal analgesia . There were no differences between the two groups in other outcomes ( return of bowel function and dietary intake , readiness to hospital discharge , and length of hospital stay ) . CONCLUSIONS When ERAS programme is used for laparoscopic colonic resection , an intrathecal mixture of bupivacaine and morphine was associated with less postoperative opioid consumption , but has no other advantages over systemic opioids", "The aim of this trial was to compare multimodal optimization with conventional perioperative management in a consecutive series of patients undergoing a wide range of colorectal procedures", "BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer", "Background Fast-track protocol s are followed by an enhanced recovery , early return to bowel function and to complete nutrition , and a reduced hospital stay . Our study was design ed to implement fast-track protocol in our university hospital . Methods The 96 consecutive patients with colorectal neoplasm included in the study were r and omized in two equal groups : group 1 ( FT ) included patients undergoing colorectal surgery in a fast-track protocol , and group 2 ( C ) included patients undergoing colorectal surgery with a conventional care protocol . As with other fast-track protocol s , our protocol included carbohydrate fluids load before operation , early mobilization and oral feeding , regular prokinetics , and multimodal postoperative analgesia . Time to restoration of bowel function , to complete mobilization and feeding , length of hospital stay , and incidence of complications and readmissions were monitored . Results Time to mobilization , restoring of bowel function , and complete oral feeding were significantly shorter with fast-track protocol ( p = 0.001 , p = 0.042 , and p = 0.01 , respectively ) . Hospital stay also was shorter in the fast-track group ( p = 0.001 ) . The incidence of complications did not significantly differ with the study groups . Conclusions In our study , fast-track protocol result ed in a shorter time to mobilization , complete feeding , and discharge from hospital . Fast-track protocol did not increase the incidence of complications . However , we consider that our data require further confirmation with powered multicenter national studies", "Background and aims Evidence demonstrating improved short-term outcomes with laparoscopic surgery compared with open surgery for colorectal cancer is accumulating . In addition , programmes optimising peri-operative care for major abdominal surgery are becoming widespread . Evaluating laparoscopic surgery and enhanced recovery programmes usually focuses on short-term recovery . The aim of this study was to compare recovery after laparoscopic and open surgery for colorectal cancer up to 1 year post-operatively , using a combination of self-report and observer data . Patients / Methods From January 2002 to March 2004 , 62 patients were r and omised ( 2:1 ) to receive laparoscopic ( n = 43 ) or open surgery ( n = 19 ) within an enhanced recovery programme . Functional outcomes up to 1 year were assessed using interview-administered question naires . Results / Findings Question naire and health-related quality of life data were obtained in over 85 % of patients . Patients undergoing laparoscopic surgery felt fully recovered and resumed driving more quickly than those having open surgery ( p = 0.016 and p = 0.048 respectively ) . Fifty-eight percent of patients having open surgery felt fully recovered by 12 months versus 88 % of laparoscopic patients .Interpretation/ Conclusion Within an enhanced recovery programme , patients undergoing laparoscopic surgery recovered more quickly than after open resection . Both approaches however , were associated with slow recovery despite a relatively short hospital stay", "Background The increasing use of laparoscopic techniques for colorectal resections means that the issue of postoperative analgesia needs to be reassessed . This nonr and omized comparative study aim ed to assess the efficacy of the transversus abdominis plane ( TAP ) block in laparoscopic colorectal resections . Methods Prospect ively collected data from consecutive patients undergoing laparoscopic colorectal resections were used . Analgesia usage and outcome data for patients who had a TAP block and a postoperative morphine patient-controlled analgesia pump ( PCA ) were compared with those for patients who had a PCA alone . Results Data for 74 patients were used in the final analysis ( 40 TAP/PCA and 34 PCA alone ) . There was a significant reduction in overall intravenous opiate use in the TAP/PCA group ( 31.3 vs. 51.8 mg ; P = 0.03 ) . The TAP/PCA group showed a slight trend toward a shorter hospital stay ( 3 vs. 4 days ; P = 0.17 ) but no difference in postoperative complications or any other outcome measure . There was no procedure-related morbidity relating to the use of TAP blocks . Conclusions It appears that TAP blocks reduce postoperative analgesia use of patients undergoing laparoscopic colorectal resections within an enhanced recovery program , and this may have an impact on their postoperative hospital length of stay", "BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p surgery ( p Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p need for fewer analgesics , and with a shorter hospital stay ( p open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon", "Background The enhanced recovery program ( ERP ) aims to reduce the metabolic response to surgery , hastening recovery and shortening hospital stay . Concerns exist regarding morbidity and hospital stay in elderly patients . The present study aim ed to compare the outcomes and compliance of elderly patients managed by an ERP protocol with a younger group . Methods A review was performed of a prospect i ve data base of patients undergoing colorectal resection managed under the ERP protocol between 2005 and 2010 . Patients were grouped into were collated . The postoperative outcomes were compared with the goals set out by the ERP protocol . Results A total of 688 patients were included , 558 were Some 96 % of operations were planned laparoscopically . Median total length of hospital stay was 6 days ( range : 1–108 days ) for the 30 day readmission rate of 8.6 % for the population and no significant differences between groups . The 30 day mortality was 5 % , with a significant difference between the two groups ( P in protocol adherence were identified in the discontinuation of intravenous fluids , catheter removal , and early mobilization . Conclusions An enhanced recovery program is feasible for colorectal surgery patients ≥80 years of age , with similar compliance as the younger group to some aspects of the protocol and an acceptable readmission rate . Attention to improving compliance in the postoperative phase is necessary , particularly in such high-risk patients , as such improvement may reduce the morbidity and mortality", "Recent advances in surgery have focused on peri‐operative care and interventions to improve outcome following surgery . Psychological preparation has a positive impact on recovery and incorporates a range of strategies with dissemination of information as one of the key elements . Information can be given verbally , through printed information or through use of a video . Traditionally , reliance has been on the use of written material as an adjunct to patient education in clinic . The current study is a r and omized trial on the use of video education in patients undergoing elective colorectal resection within an enhanced recovery programme", "Purpose This single-center prospect i ve cohort study , conducted outside of a clinical trial , tried to identify the importance of each fast-track surgery procedure and protocol adherence level on clinical outcomes after colorectal surgery . Methods From a prospect ively maintained data base , 606 patients who underwent elective laparoscopic or open colorectal resection within a well established fast-track surgery ( FT ) protocol , between 2005 and 2011 , were identified . Univariate and multivariate analysis were performed to assess the relationship between each FT procedure with an adherence rate outcome variables ( length of stay — LOS , 30-day morbidity and readmission rate ) . Patients were divided into four adherence level groups to FT procedures —100 % , 85–95 % , 70–80 % , and improved LOS and morbidity rates . Readmission rates were only significantly different between the full fast-track pathway and the less implemented groups . Multivariate analyses revealed that the fast removal of bladder catheter positively influenced length of stay ( p and 30-day morbidity ( p mobilization improved LOS ( p = 0.027 , p improved LOS ( p , morbidity ( p and readmission rate ( p = 0.011 ) . Conclusion Postoperative outcomes after colorectal surgery are directly proportional to FT protocol adherence . The early removal of the bladder catheter and early postoperative solid feeding independently influenced the length of hospital stay and 30-day morbidity rates", "Background The present study aims to examine the feasibility and safety of a two-day hospital stay after laparoscopic colorectal resection ( LCR ) under an enhanced recovery after surgery ( ERAS ) pathway . Methods Between 2003 and 2010 , 882 consecutive patients undergoing LCR were analyzed . Patients were grouped and analyzed according to whether their hospital stay was 2 days ( group A ) or longer ( group B ) . Demographic , surgical , and postoperative data were compared . To identify independent predictive factors related to a short hospital stay , a multivariate analysis was also performed . Results Group A represented 10.3 % of this series ( 91 patients ) . There were no differences regarding age , gender , BMI , ASA , and previous abdominal surgeries between groups . Group A had a lower incidence of rectal cancer and anterior resections than group B ( 6.6 vs. 17.7 % [ p = 0.006 ] and 14.3 vs. 23.4 % [ p = 0.048 ] ) , respectively , and a lower mean operative time ( 170 min vs. 192 min ; p = 0.002 ) . Group A had a lower overall morbidity rate than group B ( 5.5 vs. 16.9 % ; p = 0.004 ) and a lower incidence of surgery-related complications ( 5.5 vs. 14.9 % ; p = 0.001 ) . The overall conversion rate was 10 % ( only one patient in group A required conversion ) , and the difference in conversion rate between groups was statistically significant ( 1.2 vs. 10.7 % ; p = 0.003 ) . Group A had a lower readmission rate ( 0 vs. 4.9 % ; p = 0.089 ) . Multivariate analysis showed that conversion , postoperative morbidity , and rectal prolapse were independently associated with the length of hospital stay . Conclusions A two-day hospital stay after LCR is safe and feasible under an ERAS pathway , without compromising the readmission or complication rate", "Background Few clinical studies or r and omized clinical trial results have reported the impact of fast-track surgery on human immunity . This study aim ed to investigate the clinical and immune impact of fast-track surgery in colorectal cancer patients undergoing elective open surgery . Methods A controlled r and omized clinical trial was conducted from November 2008 to January 2009 with a 1-month postdischarge follow-up . A total of 70 patients with colorectal carcinoma requiring colorectal resection were r and omized into two groups : a fast-track group ( 35 cases ) and a conventional care group ( 35 cases ) . All included patients underwent elective open colorectal resection with combined tracheal intubation and general anesthesia . Clinical parameters and markers of immune function were evaluated in both groups postoperatively . Results In all , 62 patients completed the study : 32 in the fast-track group and 30 in the conventional care group . Our findings revealed a significantly shorter postoperative hospital stay and faster return of gastrointestinal function in patients undergoing fast-track rehabilitation . In addition , we found a quicker response of white blood cells in the fast-track group than in the conventional care group . We also found that blood levels of globulin , immunoglobulin G , and complement 4 on postoperative day 3 were higher in the fast-track group than in the conventional care group . Conclusions Fast-track surgery accelerates clinical recovery and improves postoperative immunity after elective open surgery for colorectal carcinoma", "Background The aim of the present study was to evaluate the effects of preoperative nutritional status on the short-term outcomes of an enhanced recovery after surgery ( ERAS ) programme for colorectal cancer surgery . Methods This prospect i ve observational study included 149 patients who underwent elective resection of colorectal cancer with ERAS from January 2011 to January 2014 in a university hospital . Subjective global assessment ( SGA ) was used to determine preoperative nutritional status . Primary outcomes included the length of postoperative stay , postoperative morbidity , gastrointestinal recovery , and 30-day readmission . Results The patients were divided into 3 groups according to the SGA classification . There were 96 patients ( 64.4 % ) in SGA-A ( well-nourished ) , 48 ( 32.2 % ) in SGA-B ( mild to moderately malnourished ) , and 5 ( 3.4 % ) in SGA-C ( severely malnourished ) . Patients in SGA-A had the median length of postoperative stay of 4 days ( range 2–23 ) , which was significantly shorter compared to SGA-B ( 5 days ; range 2–16 ; p The overall complication rates of SGA-A , SGA-B , and SGA-C patients were 11 , 31 % ( adjusted OR 3.76 ; 95 % CI 1.36–10.36 ; p 0.66 ) . Mean time to resumption of normal diet and time to first defecation were 1.6 ± 1.3 and 2.2 ± 0.9 days in SGA-A , 2.6 ± 1.7 and 3.1 ± 1.6 days in SGA-B ( p respectively ) . No 30-day mortality occurred in any group . One patient in SGA-A ( 1 % ) , and 3 patients in SGA-B ( 6 % ) had unplanned 30-day re-admission ; p = 0.11 . Conclusions Within an ERAS programme for colorectal cancer surgery , malnourished patients were at risk for increased postoperative morbidity , delayed recovery of gastrointestinal function , and prolonged length of hospital stay", "A r and omized controlled trial was conducted to test the hypothesis that there is no difference in complications in patients receiving intravenous ( iv ) water and electrolyte , based on either stroke volume or clinical indicators at bowel surgery", "Background Despite using laparoscopy and enhanced recovery pathways ( ERP ) , some patients are not ready for early discharge . The goal of this study was to identify predictors for patients who might fail early discharge , so that any defined factors might be addressed and optimized . Methods A prospect ively maintained data base was review ed for major elective laparoscopic colorectal surgical procedures . Cases were divided into day of discharge groups : ≤3 days and > 4 days . All followed a st and ardized ERP . Demographic and clinical data were compared using Student ’s paired t tests or Fisher ’s exact test , with p value 275 ≤3 days patients and 273 > 4 days patients . There were significant differences between groups in body mass index ( p = 0.0123 ) , comorbidities ( p = 0.0062 ) , ASA class ( p = 0.0014 ) , operation time ( p postoperative complications ( p and 30-day reoperation rate ( p = 0.0004 ) . There were no significant differences for intraoperative complications ( p = 0.724 ) , readmissions ( p = 0.187 ) , or mortality rate ( p = 1.00 ) . Significantly more patients were discharged directly home in the ≤3-days cohort . Using logistic regression , every hour of operating time increased the risk of length of stay > 4 days by 2.35 % . Conclusions Elective colorectal surgery patients with longer operation times and more comorbidities are more likely to fail early discharge . These patients should have different expectations of the ERP , as an expected 1- to 3-day stay may not be achievable . By identifying patients at risk for failing early discharge , re sources and postoperative support can be better allocated and patients better informed about likely recovery", "Background The aim of this trial was to compare the Enhanced Recovery After Surgery ( ERAS ) program with conventional perioperative management in patients who underwent radical resection for colorectal cancer . Methods A combination of evidence -based and consensus methodology was used to develop the ERAS protocol . Five hundred ninety-seven consecutive patients who underwent elective colorectal resection were r and omized to either the ERAS ( n = 299 ) or the control group ( n = 298 ) . Outcomes relating to nutrition and metabolism index , stress index , and recovery index were measured and recorded . Results Demographic and operative data were similar between the two groups . Patients in the ERAS group showed improved nutritional status when compared with those of the control group . On postoperative day ( POD ) 1 , the HOMA-IR ( insulin resistance index ) of the ERAS group was lower than that of the control group ( p The cortisol level of the control group was elevated on both POD 1 ( p = 0.007 ) and POD 5 ( p = 0.002 ) compared to the preoperative level . However , the cortisol level of the ERAS group was not increased until POD 5 ( p = 0.001 ) . Reduced levels of TNF-α , IL-1β , IL-6 , and IFN-γ in the ERAS group indicated less postoperative stress responses . In addition , ERAS was associated with accelerated recovery of gastrointestinal function . The postoperative length of stay ( p ERAS protocol attenuates the surgical stress response and accelerates postoperative recovery without compromising patient safety", "BACKGROUND Low concentrations of albumin in serum and long gastric emptying times have been returned to normal in dogs by salt and water restriction , or a high protein intake . We aim ed to determine the effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection in human beings . METHODS We r and omly allocated ten patients to receive postoperative intravenous fluids in accordance present hospital practice ( > or = 3 L water and 154 mmol sodium per day ) and ten to receive a restricted intake ( water and 77 mmol sodium per day ) . All patients had no disease other than colonic cancer . The primary endpoint was solid and liquid-phase gastric emptying time , measured by dual isotope radionuclide scintigraphy on the fourth postoperative day . Secondary endpoints included time to first bowel movement and length of postoperative hospital stay . Analysis was by intention to treat . FINDINGS Median solid and liquid phase gastric emptying times ( T(50 ) ) on the fourth postoperative day were significantly longer in the st and ard group than in the restricted group ( 175 vs 72.5 min , difference 56 [ 95 % CI 12 - 132 ] , p=0.028 ; and 110 vs 73.5 min , 52 [ 9 - 95 ] , p=0.017 , respectively ) . Median passage of flatus was 1 day later ( 4 vs 3 days , 2 [ 1 - 2 ] , p=0.001 ) ; median passage of stool 2.5 days later ( 6.5 vs 4 days , 3 [ 2 - 4 ] , p=0.001 ) ; and median postoperative hospital stay 3 days longer ( 9 vs 6 days , 3 [ 1 - 8 ] , p=0.001 ) in the st and ard group than in the restricted group . One patient in the restricted group developed hypokalaemia , whereas seven patients in the st and ard group had side-effects or complications ( p=0.01 ) . INTERPRETATION Positive salt and water balance sufficient to cause a 3 kg weight gain after surgery delays return of gastrointestinal function and prolongs hospital stay in patients undergoing elective colonic resection", "BACKGROUND : Despite laparoscopy and enhanced recovery pathways , some patients do not attain early discharge . Frailty is generally accepted as a marker of increased risk , complications , and mortality . Frailty may have the potential to identify patient outcomes . PURPOSE : The aim of this study was to evaluate frailty as a predictor of patients who might fail early discharge . SETTING : This study was conducted at a tertiary referral center . DESIGN : This was a case-matched study . PATIENTS : Elective abdominal laparoscopic colorectal cases from 2009 to 2012 were selected . METHODS : Review of a prospect i ve data base matched all cases with a postoperative day of discharge of ⩽3 days to a > 3 day of discharge cohort . All patients followed a st and ardized enhanced recovery pathway . STATISTICAL ANALYSIS : Categorical and ordinal variables were analyzed with the Student t test or Fisher exact test , and correspondence analysis evaluated the relationship between length of stay and the Modified Frailty Index . MAIN OUTCOME MEASURE : The primary outcome measure was the relationship between length of stay and the Modified Frailty Index . RESULTS : There were 464 ⩽3 day and 388 > 3 day patients . The groups were similar in demographics and comorbidities . There were significant differences in the Modified Frailty Index ( p ( p 0.01 ) , postoperative complications ( p 0.01 ) , 30-day readmissions ( p = 0.03 ) , and 30-day reoperation rate ( p Modified Frailty Index was indicative of longer length of stay . A Modified Frailty Index of 0 was strongly related to a length of stay 0 to 3 days , and a Modified Frailty Index of 2 was strongly related to a 8- to 14-day stay . LIMITATIONS This was a single-center study performed on a retrospective data set . CONCLUSIONS : Patients undergoing elective colorectal surgery with a higher Modified Frailty Index were more likely not to attain early discharge . Despite similar demographics , the Modified Frailty Index could discriminate between patient outcomes , and correlated with longer operating times , length of stay , and readmissions . By using a prospect i ve score to identify patients at risk for not achieving early discharge preoperatively , re sources and postoperative support can be better allocated", "PURPOSE Laparoscopic resection and a multimodal approach known as an enhanced recovery program ( ERP ) have been major changes in colorectal perioperative care that have improved clinical outcomes for colorectal cancer resection . EnROL ( Enhanced Recovery Open Versus Laparoscopic ) is a multicenter r and omized controlled trial examining whether the benefits of laparoscopy still exist when open surgery is optimized within an ERP . PATIENTS AND METHODS Adults with colorectal cancer suitable for elective resection were r and omly assigned at a ratio of 1:1 to laparoscopic or open surgery within an ERP , stratified by center , cancer site ( colon v rectum ) , and age group ( 75 years ) using minimization . The primary outcome was physical fatigue at 1 month postsurgery . Secondary outcomes included hospital stay , complications , other patient-reported outcomes ( PROs ) , and physical function . Patients and outcome assessors were blinded until 7 days postsurgery or discharge if earlier . Central independent and blinded pathologic assessment of surgical quality was undertaken . RESULTS A total of 204 patients ( laparoscopy , n=103 ; open surgery , n=101 ) were recruited from 12 UK centers from July 2008 to April 2012 . One-month physical fatigue scores were similar in both groups ( mean : laparoscopy , 12.28 ; 95 % CI , 11.37 to 13.19 v open surgery , 12.05 ; 95 % CI , 11.14 to 12.96 ; adjusted mean difference , -0.23 ; 95 % CI , -1.52 to 1.07 ) . Median total hospital stay was significantly shorter after laparoscopic surgery ( median : laparoscopy , 5 ; interquartile range [ IQR ] , 4 to 9 v open surgery , 7 ; IQR , 5 to 11 days ; P=.033 ) . There were no differences in other secondary outcomes or in specimen quality after central pathologic review . CONCLUSION In patients treated by experienced surgeons within an ERP , physical fatigue and other PROs were similar in both groups , but laparoscopic surgery significantly reduced length of hospital stay", " Multimodal optimization of surgical care has been associated with reduced hospital stay and improved physical function . The aim of this r and omized trial was to compare multimodal optimization with st and ard care in patients undergoing colonic resection", "OBJECTIVE To investigate the feasibility of a 48-hour postoperative stay program after colonic resection . SUMMARY BACKGROUND DATA Postoperative hospital stay after colonic resection is usually 6 to 12 days , with a complication rate of 10 % to 20 % . Limiting factors for early recovery include stress-induced organ dysfunction , paralytic ileus , pain , and fatigue . It has been hypothesized that an accelerated multimodal rehabilitation program with optimal pain relief , stress reduction with regional anesthesia , early enteral nutrition , and early mobilization may enhance recovery and reduce the complication rate . METHODS Sixty consecutive patients undergoing elective colonic resection were prospect ively studied using a well-defined postoperative care program including continuous thoracic epidural analgesia and enforced early mobilization and enteral nutrition , and a planned 48-hour postoperative hospital stay . Postoperative follow-up was scheduled at 8 and 30 days . RESULTS Median age was 74 years , with 20 patients in ASA group III-IV . Normal gastrointestinal function ( defecation ) occurred within 48 hours in 57 patients , and the median hospital stay was 2 days , with 32 patients staying 2 days after surgery . There were no cardiopulmonary complications . The readmission rate was 15 % , including two patients with anastomotic dehiscence ( one treated conservatively , one with colostomy ) ; other readmissions required only short-term observation . CONCLUSION A multimodal rehabilitation program may significantly reduce the postoperative hospital stay in high-risk patients undergoing colonic resection . Such a program may also reduce postoperative ileus and cardiopulmonary complications . These results may have important implication s for the care of patients after colonic surgery and in the future assessment of open versus laparoscopic colonic resection", "Objective : To investigate which perioperative treatment , ie , laparoscopic or open surgery combined with fast track ( FT ) or st and ard care , is the optimal approach for patients undergoing segmental resection for colon cancer . Summary Background Data : Important developments in elective colorectal surgery are the introduction of laparoscopy and implementation of FT care , both focusing on faster recovery . Methods : In a 9-center trial , patients eligible for segmental colectomy were r and omized to laparoscopic or open colectomy , and to FT or st and ard care , result ing in 4 treatment groups . Primary outcome was total postoperative hospital stay ( THS ) . Secondary outcomes were postoperative hospital stay ( PHS ) , morbidity , reoperation rate , readmission rate , in-hospital mortality , quality of life at 2 and 4 weeks , patient satisfaction and in-hospital costs . Four hundred patients were required to find a minimum difference of 1 day in hospital stay . Results : Median THS in the laparoscopic/FT group was 5 ( interquar-tile range : 4–8 ) days ; open/FT 7 ( 5–11 ) days ; laparoscopic/st and ard 6 ( 4.5–9.5 ) days , and open/st and ard 7 ( 6–13 ) days ( P Median PHS in the laparoscopic/FT group was 5 ( 4–7 ) days ; open/FT 6 ( 4.5–10 ) days ; laparoscopic/st and ard 6 ( 4–8.5 ) days and open/st and ard 7 ( 6–10.5 ) days ( P reduce hospital stay and morbidity . Conclusions : Optimal perioperative treatment for patients requiring segmental colectomy for colon cancer is laparoscopic resection embedded in a FT program . If open surgery is applied , it is preferentially done in FT care . This study was registered under NTR222 ( www.trialregister.nl )", "Background : The preoperative period ( prehabilitation ) may represent a more appropriate time than the postoperative period to implement an intervention . The impact of prehabilitation on recovery of function al exercise capacity was thus studied in patients undergoing colorectal resection for cancer . Methods : A parallel-arm single-blind superiority r and omized controlled trial was conducted . Seventy-seven patients were r and omized to receive either prehabilitation ( n = 38 ) or rehabilitation ( n = 39 ) . Both groups received a home-based intervention of moderate aerobic and resistance exercises , nutritional counseling with protein supplementation , and relaxation exercises initiated either 4 weeks before surgery ( prehabilitation ) or immediately after surgery ( rehabilitation ) , and continued for 8 weeks after surgery . Patients were managed with an enhanced recovery pathway . Primary outcome was functional exercise capacity measured using the vali date d 6-min walk test . Results : Median duration of prehabilitation was 24.5 days . While awaiting surgery , functional walking capacity increased ( ≥20 m ) in a higher proportion of the prehabilitation group compared with the rehabilitation group ( 53 vs. 15 % , adjusted P = 0.006 ) . Complication rates and duration of hospital stay were similar . The difference between baseline and 8-week 6-min walking test was significantly higher in the prehabilitation compared with the rehabilitation group ( + 23.7 m [ SD , 54.8 ] vs. −21.8 m [ SD , 80.7 ] ; mean difference 45.4 m [ 95 % CI , 13.9 to 77.0 ] ) . A higher proportion of the prehabilitation group were also recovered to or above baseline exercise capacity at 8 weeks compared with the rehabilitation group ( 84 vs. 62 % , adjusted P = 0.049 ) . Conclusion : Meaningful changes in postoperative functional exercise capacity can be achieved with a prehabilitation program ", "INTRODUCTION Laparoscopic surgery is well established in the modern management of colorectal disease . More recently , enhanced recovery after surgery ( ERAS ) protocol s have been introduced to further promote accelerated discharge and faster recovery . However , not all patients are suitable for early discharge . The purpose of this study was to evaluate the early outcomes of patients undergoing such a regime to determine which peri-operative factors may predict safe accelerated discharge . METHODS Data were prospect ively collected on consecutive patients undergoing laparoscopic colorectal surgery . All patients followed the institution 's ERAS protocol and were discharged once specific criteria were fulfilled . Clinical characteristics and outcomes were compared between patients who were discharged before and after 72 h post-surgery . Thereafter , the peri-operative factors that were associated with delayed discharge were determined using a binary logistic model . RESULTS Three hundred patients were included in the analysis . The most common operation was laparoscopic anterior resection ( n = 123 , 41 % ) . Mean length of stay was 4.8 days ( st and ard deviation 5.9 ) , with 185 ( 62 % ) patients discharged within 72 h. Ten ( 3 % ) patients had a post-operative complication . Three independent predictors of delayed discharge were identified ; BMI ( OR 1.06 , 95%CI 1.01 - 1.11 ) , operation length ( OR 0.99 , 95%CI 0.98 - 0.99 ) and complications ( OR 16.26 , 95%CI 4.88 - 54.08 ) . CONCLUSIONS A combined approach of laparoscopic surgery and ERAS leads to reduced length of stay . This enables more than 60 % of patients to be discharged within 72 h. Increased BMI , duration of operation and complications post-operatively independently predict a longer length of stay", "BACKGROUND : Cyclo-oxygenase 2 inhibitors can be used for pain treatment after colorectal surgery . OBJECTIVE : The aim of this study was to investigate whether the use of etoricoxib has negative effects on the perioperative outcome in colorectal surgery . DESIGN : Complication data from an advanced medical data base system were sample d prospect ively , and patient records were review ed retrospectively . PATIENTS : All patients with elective colorectal surgery within an enhanced recovery after surgery protocol from 2008 to 2009 were selected . INTERVENTION : The nonr and omized use of perioperative etoricoxib treatment was compared with a control group . MAIN OUTCOME MEASURES : The primary outcome measured was the number of patients with postoperative complications according to the Dindo-Clavien classification . RESULTS : One hundred one patients received etoricoxib treatment , whereas 104 did not . The patient groups were very comparable . We observed a significant increase in the number of patients with postoperative complications with etoricoxib treatment ( 43 vs 30 patients ; 42.6 % vs 28.8 % , p = 0.041 ) due to an increase in patients with a major complication ( Dindo-Clavien complication grade III – V : 22.8 % vs 9.6 % , p = 0.01 ) . Patients with etoricoxib treatment and a complication needed a longer recovery period than patients with a complication in the control group ( 18 ( 17 ; 20 ) vs 14 ( 13 ; 15 ) days , p = 0.05 ) . We observed an increased level of postoperative serum creatinine with etoricoxib treatment ( 105 ( 98 ; 112 ) vs 82 ( 78 ; 85 ) , p = 0.003 ) , which was more pronounced in patients with a complication ( 141 ( 127 ; 155 ) vs 91 ( 83 ; 98 ) , p = 0.002 ; 25 vs 8 patients with serum creatinine > 100 & mgr;mol/L , p = 0.008 ) . In multivariate analysis , etoricoxib was identified as an independent risk factor for experiencing a major complication with a risk increase of approximately 2.5-fold ( p = 0.03 ) . LIMITATIONS : This study was limited by the nonr and omized use of perioperative etoricoxib and the retrospective nature of its review of patient records . CONCLUSIONS : Etoricoxib increased the number of patients with postoperative complications and should be considered carefully in colorectal surgery", "Abstract INTRODUCTION : In an era of dwindling hospital re sources and increasing medical costs , safe reduction in postoperative stay has become a major focus to optimize utilization of healthcare re sources . Although several protocol s have been reported to reduce postoperative stay , no Level I evidence exists for their use in routine clinical practice . METHODS : Sixty-four patients undergoing laparotomy and intestinal or rectal resection were r and omly assigned to a pathway of controlled rehabilitation with early ambulation and diet or to traditional postoperative care . Time to discharge from hospital , complication and readmission rates , pain level , quality of life , and patient satisfaction scores were determined at the time of discharge and at 10 and 30 days after surgery . Subgroups were defined to evaluate those who derived the optimal benefit from the protocol . RESULTS : Pathway patients spent less total time in the hospital after surgery ( 5.4 vs. 7.1 days ; P = 0.02 ) and less time in the hospital during the primary admission than traditional patients . Patients younger than 70 years old had greater benefits than the overall study group ( 5 vs. 7.1 days ; P = 0.01 ) . Patients treated by surgeons with the most experience with the pathway spent significantly less time in the hospital than did those whose surgeons were less experienced with the pathway ( P = 0.01 ) . There was no difference between pathway and traditional patients for readmission or complication rates , pain score , quality of life after surgery , or overall satisfaction with the hospital stay . CONCLUSIONS : Patients scheduled for a laparotomy and major intestinal or rectal resection are suitable for management by a pathway of controlled rehabilitation with early ambulation and diet . Pathway patients have a shorter hospital stay , with no adverse effect on patient satisfaction , pain scores , or complication rates . Patients younger than 70 years of age derive the optimal benefit , and increased surgeon experience improves outcome", "Objective : A prospect i ve r and omized controlled trial ( RCT ) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer . Aims : This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT . Methods : Patients for elective resection for colorectal cancer were offered trial entry . Participants were stratified by sex and requirement for a total mesorectal excision and central ly r and omized . Multimodal patients received intravenous fluid restriction , unrestricted oral intake with prokinetic agents , early ambulation , and fixed regimen epidural analgesia . Control patients received intravenous fluids to prevent oliguria , restricted oral intake until return of bowel motility , and weaning regimen epidural analgesia . Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets . Discharge decision was made using preagreed criteria . The primary endpoint was postoperative stay , and achievement of independence milestones . Secondary endpoints were postoperative complications , readmission rates , and mortality . Analysis was by intention to treat . Results : Seventy patients were recruited . Approximately one fourth underwent TME . Median ages were similar ( 69.3 vs. 73.0 years ) . The median stay was significantly reduced in the multimodal group ( 5 vs. 7 days ; P control arm were 2.5 times as likely to require a postoperative stay of more than 5 days . Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions . There were 2 deaths , both controls . Conclusions : This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery . Morbidity and mortality are not increased", "PURPOSE : Although laparoscopic surgery may permit earlier recovery compared with open surgery , no published r and omized controlled trial has investigated the benefit of a multimodal rehabilitation program after laparoscopic colonic resection . This study aim ed to evaluate the efficacy of a rehabilitation program after laparoscopic colon surgery in the context of a r and omized controlled trial . METHODS : Between September 2007 and October 2009 , 100 patients who had received laparoscopic colon surgery were selected for the study and r and omly assigned on a 1:1 basis to a rehabilitation program group with early mobilization and diet ( n = 46 ) or conventional care group ( n = 54 ) . The rehabilitation program group received early oral feeding , early ambulation , and regular laxative . The primary outcome was recovery time , measured with criteria of tolerable diet for 24 hours , safe ambulation , analgesic-free , and afebrile status without major complications . Secondary outcomes were postoperative hospital stay , complications , quality of life by Short Form 36 , pain by visual analog scale , and readmission . This study was registered ( ID number NCT00606944 , http://register . clinical trials.gov ) . RESULTS : Recovery time was shorter in the rehabilitation program group than in the conventional care group ( median ( interquartile range ) , 4 ( 3–5 ) d vs 6 ( 5–7 ) d , respectively ; P in postoperative hospital stay between the 2 groups ( rehabilitation program group , 7 ( 6–8 ) d vs conventional care group , 8 ( 7–9 ) d ; P = .065 ) . There was no difference in complication rates between the rehabilitation program group and conventional care group ( 10.9 % vs 20.4 % , respectively ; P = .136 ) . Quality of life and pain were similar in both groups . There were no readmissions or mortality . CONCLUSIONS : A rehabilitation program with early mobilization and diet after laparoscopic colon surgery results in reduced recovery time without increased complications . These results suggest that a multimodal rehabilitation program may increase the short-term benefits after laparoscopic colon surgery", "BACKGROUND : There is an increasing trend to use laparoscopy for rectal cancer surgery . Although laparoscopic and open rectal resections appear oncologically equivalent , there is little information on the cost of different surgical approaches . With the current health care crisis and the importance of optimizing health care re sources and patient outcomes , the cost of care is an important factor . OBJECTIVE : The aim of this study was to evaluate the cost-effectiveness of laparoscopy in rectal cancer . DESIGN : This was a case-matched study . SETTING S : This study was conducted at a tertiary referral center . PATIENTS : Patients undergoing elective rectal cancer resection between 2007 and 2012 were selected . METHODS : A review of a prospect i ve data base for elective laparoscopic rectal cancer resections was performed . Laparoscopic cases were matched to open cases based on age , BMI , operative procedure , and diagnostic-related group . MAIN OUTCOME MEASURES : The primary outcomes measured were the cost of care , hospital length of stay , discharge disposition , readmission , postoperative complications , and mortality rates . RESULTS : Two hundred fifty-four matched cases were included in the analysis : 125 laparoscopic ( 49 % ) and 129 open ( 51 % ) . The cTNM stage ( p = 0.39 ) , tumor distance from the anal verge ( p = 0.07 ) , and rate of neoadjuvant therapy received between the laparoscopic and open groups were similar ( p = 0.12 ) . Operating time ( p cost per operating room minute ( p = 0.04 ) were significantly higher in the open group . The groups were oncologically equivalent , based on circumferential resection margin ( p = 0.15 ) . The laparoscopic group had a significantly shorter length of stay ( p lower total hospital cost ( p Postoperative complications , 30-day readmission , reoperation , and mortality rates were similar . However , significantly more patients undergoing open resection required intensive care unit care ( p = 0.03 ) , skilled nursing ( p = 0.03 ) , or home care services ( p Laparoscopy is cost-effective for rectal cancer surgery , improving both health care expenditures and patient outcomes . For selected patients , laparoscopic rectal cancer resection can reduce length of stay , operating time , and re source utilization ", "Background and Objective : Laparoscopy , thoracic epidural analgesia , and enhanced recovery program ( ERP ) have been shown to be the major elements to facilitate the postoperative recovery strategy in open colorectal surgery . This study compared the effect of intraoperative and postoperative intravenous ( IV ) lidocaine infusion with thoracic epidural analgesia on postoperative restoration of bowel function in patients undergoing laparoscopic colorectal resection using an ERP . Methods : Sixty patients scheduled for elective laparoscopic colorectal surgery were prospect ively r and omized to receive either thoracic epidural analgesia ( TEA group ) or IV lidocaine infusion ( IL group ) ( 1 mg/kg per hour ) with patient-controlled analgesia morphine for the first 48 hours after surgery . All patients received a similar ERP . The primary outcome was time to return of bowel function . Postoperative pain intensity , time out of bed , dietary intake , duration of hospital stay , and postoperative complications were also recorded . Results : Mean times and SD ( 95 % confidence interval ) to first flatus ( TEA , 24 [ SD , 11 ] [ 19 - 29 ] hrs vs IL , 27 [ SD , 12 ] [ 22 - 32 ] hrs ) and to bowel movements ( TEA , 44 ±19 [ 35 - 52 ] hrs vs IL , 43 [ SD , 20 ] [ 34 - 51 ] hrs ) were similar in both groups ( P = 0.887 ) . Thoracic epidural analgesia provided better analgesia in patients undergoing rectal surgery . Time out of bed and dietary intake were similar . Patients in the TEA and IL groups were discharged on median day 3 ( interquartile range , 3 - 4 days ) , P = 0.744 . Sixty percent of patients in both groups left the hospital on day 3 . Conclusions : Intraoperative and postoperative IV infusion of lidocaine in patients undergoing laparoscopic colorectal resection using an ERP had a similar impact on bowel function compared with thoracic epidural analgesia", "BACKGROUND Enhanced Recovery Programmes ( ERPs ) have been shown to benefit recovery following major surgery in selected centres and patient groups , but their wider applicability requires continued evaluation . The aims of this study were to assess the outcomes of the first 400 consecutive , non-selected patients , undergoing major elective colorectal surgery within an Enhanced Recovery programme at a UK District General hospital and to examine the effects of patient risk factors and operative approach on outcomes . METHODS Since September 2005 all patients undergoing major elective colon and rectal surgery at our hospital have been treated within an ERP and their data recorded prospect ively on a data base . Safety and efficacy outcomes for the first 400 patients were compared using SPSS v14.0 with both a retrospective , pre-ERP group ; and according to patient risk factors and operative approaches . RESULTS Median length of stays ( LOS ) reduced from 9 days ( IQR 7 - 11 ) to 6 days ( IQR 5 - 10 ) after introduction of the ERP ( p in LOS were observed between elderly ( ≥80 years ) and younger patients or between different BMI groups . American Society of Anesthesiologists ( ASA ) grade 3 patients demonstrated significantly longer median LOS than those with ASA grade s 1 and 2 . Patients undergoing laparoscopic surgery had median LOS of 6 days ( IQR 4 - 8 ) compared to 7 days ( IQR 5 - 10 ) for open procedures ( p in morbidity or mortality were observed between the groups . CONCLUSIONS Unselected application of an ERP in our unit has been associated with reductions in post-operative LOS . The ERP was safe and effective when applied to all our study patients independent of age and BMI . Despite LOS being longer in ASA grade 3 patients , application of the ERP to this higher risk group was not associated with significantly increased morbidity or mortality . Laparoscopic surgery result ed in additional modest reductions in LOS compared to open surgery within the ERP", "BACKGROUND To evaluate readmissions to determine predictors and patterns of readmission . METHODS Prospect i ve data base review identified readmitted and non-readmitted patients after colorectal surgery . Variables for the index and readmission episode were examined . RESULTS A total of 212 readmissions and 3,292 nonreadmissions were analyzed . The majority was elective . Readmitted patients were older ( P = .003 ) , had more comorbidities ( P operative times ( P length of stay ( P costs ( P = .002 ) . At the time of discharge , more readmitted patients required temporary nursing ( P American Society of Anesthesiologists score , previous abdominal operation , intensive care unit stay , and dysmotility/constipation surgery . At the time of readmission , 29.2 % required reoperation . More than half had an open procedure initially ( 55.2 % ) . After initial open procedures , reoperative time ( P = .05 ) and LOS were longer ( P = .028 ) , and more patients required temporary nursing care at the time of discharge ( P = .046 ) . Readmissions caused an additional mean hospital cost of $ 12,670.89 . CONCLUSIONS Readmitted patients have distinct demographic and outcomes variables . As most were elective cases , stratifying patients preoperatively may enable perioperative planning for this higher risk group", "BACKGROUND Enhanced Recovery Pathways ( ERPs ) have demonstrated reduced hospital length of stay and improved outcomes after colorectal surgery . Concerns exist about increases in readmission rates . Laparoscopic colorectal surgery with an ERP can permit earlier discharge without compromising safety or increasing readmission rates . STUDY DESIGN A review of a prospect i ve data base was performed for major elective colorectal procedures by a single surgeon . All patients followed a st and ardized ERP and discharge criteria . Patients were categorized by approach and day of discharge ( DoD ) of ≤ 1 , ≤ 2 , ≤ 3 , ≤ 7 , and > 7 days . Main outcomes measures were length of stay and 30-day readmission rates in each group . RESULTS Eight hundred and six cases ( 609 laparoscopic , 197 open ) were identified during a 64-month period . Mean age was similar for the laparoscopic ( 59.1 years ) and open ( 58.3 years ) groups . Mean overall DoD was at 5 days ( ± 4.8 days ) ; by approach , the mean laparoscopic DoD was at 3.9 days and open DoD was at 8.4 days . Twenty-nine percent were discharged within 48 hours ( 38 % laparoscopic and 8 % open ) and 50 % were discharged within 72 hours ( 62 % laparoscopic and 19 % open ) . Only 8.9 % of all patients ( n = 72 ) were readmitted ( 7.2 % laparoscopic , 14.2 % open ) . The cumulative readmission rate for laparoscopic patients in early DoD groups postoperative days 1 , 2 , and 3 were 0.2 % , 1.6 % , and 3.4 % , respectively . CONCLUSIONS Combining laparoscopy with an ERP optimizes patient care in colorectal surgery . The combination permits early discharge ; 38 % were discharged within 2 days and 62 % within 3 days of surgery , with low readmission rates . These results support that early DoD is possible without compromising patient safety or increasing readmission rates . This might be a marker for low readmission rate , and suggests that readmission rate alone might not be an adequate marker of quality", "Background This review aims to present a consensus for optimal perioperative care in colonic surgery and to provide grade d recommendations for items for an evidence d-based enhanced perioperative protocol . Methods Studies were selected with particular attention paid to meta-analyses , r and omised controlled trials and large prospect i ve cohorts . For each item of the perioperative treatment pathway , available English- language literature was examined , review ed and grade d. A consensus recommendation was reached after critical appraisal of the literature by the group . Results For most of the protocol items , recommendations are based on good- quality trials or meta-analyses of good- quality trials ( quality of evidence and recommendations according to the GRADE system ) . Conclusions Based on the evidence available for each item of the multimodal perioperative care pathway , the Enhanced Recovery After Surgery ( ERAS ) Society , International Association for Surgical Metabolism and Nutrition ( IASMEN ) and European Society for Clinical Nutrition and Metabolism ( ESPEN ) present a comprehensive evidence -based consensus review of perioperative care for colonic surgery" ]	411834f2-06ff-11f0-808a-c43d1ab1c353
One reason for doing r and omised controlled trials ( RCTs ) is that experiments can be convincing . Early epidemiological experimenters , such as Jenner and the smallpox vaccine and Snow and his famous Broad Street pump h and le , already knew the answer they were demonstrating ; they used the experiments as knowledge translation devices to convince others . More sophisticated modern experiments include cluster r and omised controlled trials ( C RCTs ) for experiments in the public health setting . The knowledge translation value remains : RCTs and C RCTs can potentially stimulate changes of practice among stakeholders . Capitalising on the knowledge translation value of RCTs requires more than the st and ard reporting of trials . Those who are convinced by a trial and want to act , need to know how the trial relates to their own context , what contributed to success , and what might make it even more effective . Implementation research unpacks the back-story , examining how and why an intervention worked . The Camino Verde trial of community mobilisation for control of dengue reported a significant impact on entomological indices of the Aedes aegypti vector , and on serological dengue virus infection and self-reported dengue cases . This important study should lead to studies of similar interventions in other context s , and ultimately to changes in dengue control practice s. This supplement is the back-story of the trial , providing information to help research ers and planners to make use of the trial findings . Background articles include the full protocol , a systematic review of C RCTs of approaches for Aedes aegypti control , epidemiological and entomological findings from the baseline survey , and how baseline findings were used to set up the intervention . Secondary analyses of the entomological findings examine associations with the use of the larvicide temephos , and the impact of the intervention in different conditions of water supply and seasons . Other articles describe implementation and other impacts : the underlying approach ; implementation in the trial ’s different social context s ; the different impact in women and men ; the effects of using fish for vector control ; the impact on household costs of personal protection and of cases of dengue illness ; and ethical issues . We hope this supplement will increase the knowledge translation value of the Camino Verde trial	[ "Objective To test whether community mobilization adds effectiveness to conventional dengue control . Design Pragmatic open label parallel group cluster r and omized controlled trial . Those assessing the outcomes and analyzing the data were blinded to group assignment . Central ized computerized r and omization after the baseline study allocated half the sites to intervention , stratified by country , evidence of recent dengue virus infection in children aged 3 - 9 , and vector indices . Setting R and om sample of communities in Managua , capital of Nicaragua , and three coastal regions in Guerrero State in the south of Mexico . Participants Residents in a r and om sample of census enumeration areas across both countries : 75 intervention and 75 control clusters ( about 140 households each ) were r and omized and analyzed ( 60 clusters in Nicaragua and 90 in Mexico ) , including 85 182 residents in 18 838 households . Interventions A community mobilization protocol began with community discussion of baseline results . Each intervention cluster adapted the basic intervention — chemical-free prevention of mosquito reproduction — to its own circumstances . All clusters continued the government run dengue control program . Main outcome measures Primary outcomes per protocol were self reported cases of dengue , serological evidence of recent dengue virus infection , and conventional entomological indices ( house index : households with larvae or pupae/households examined ; container index : containers with larvae or pupae/containers examined ; Breteau index : containers with larvae or pupae/households examined ; and pupae per person : pupae found/number of residents ) . Per protocol secondary analysis examined the effect of Camino Verde in the context of temephos use . Results With cluster as the unit of analysis , serological evidence from intervention sites showed a lower risk of infection with dengue virus in children ( relative risk reduction 29.5 % , 95 % confidence interval 3.8 % to 55.3 % ) , fewer reports of dengue illness ( 24.7 % , 1.8 % to 51.2 % ) , fewer houses with larvae or pupae among houses visited ( house index ) ( 44.1 % , 13.6 % to 74.7 % ) , fewer containers with larvae or pupae among containers examined ( container index ) ( 36.7 % , 24.5 % to 44.8 % ) , fewer containers with larvae or pupae among houses visited ( Breteau index ) ( 35.1 % , 16.7 % to 55.5 % ) , and fewer pupae per person ( 51.7 % , 36.2 % to 76.1 % ) . The numbers needed to treat were 30 ( 95 % confidence interval 20 to 59 ) for a lower risk of infection in children , 71 ( 48 to 143 ) for fewer reports of dengue illness , 17 ( 14 to 20 ) for the house index , 37 ( 35 to 67 ) for the container index , 10 ( 6 to 29 ) for the Breteau index , and 12 ( 7 to 31 ) for fewer pupae per person . Secondary per protocol analysis showed no serological evidence of a protective effect of temephos . Conclusions Evidence based community mobilization can add effectiveness to dengue vector control . Each site implementing the intervention in its own way has the advantage of local customization and strong community engagement . Trial registration IS RCT", "Background Dengue is a serious public health problem with an important economic impact . This study used data from a cluster r and omised controlled trial of community mobilisation for dengue prevention to estimate the household costs of treatment of dengue illness . It examined the economic impact of the trial intervention in the three coastal regions of Mexico ’s Guerrero State . Methods The 2010 baseline survey covered households in a r and om sample of 90 clusters in the coastal regions ; the clusters were r and omly allocated to intervention or control and re-surveyed in 2012 . The surveys asked about dengue cases in the last 12 months , expenditures on their treatment , and work or school days lost by patients and care givers . We did not assign monetary value to days lost , since a lost day to a person of low earning power is of equal or higher value to that person than to one who earns more . Results The 12,312 households in 2010 reported 1020 dengue cases in the last 12 months ( 1.9 % of the sample population ) . Most ( 78 % ) were ambulatory cases , with a mean cost of USD 51 and 10.8 work/school days , rising to USD 96 and 11.4 work/school days if treated by a private physician . Hospitalised cases cost USD 28–94 in government institutions and USD 392 in private hospitals ( excluding additional inpatient charges ) , as well as 9.6–17.3 work/school days . Dengue cases cost households an estimated 412,825 work/school days throughout the three coastal regions . In the follow up survey , 6.1 % ( 326/5349 ) of households in intervention clusters and 7.9 % ( 405/5139 ) in control clusters reported at least one dengue case . The mean of days lost per case was similar in intervention and control clusters , but the number of days lost from dengue and all elements of costs for dengue cases per 1000 population were lower in intervention clusters . If the total population of the three coastal regions had received the intervention , some 149,401 work or school days lost per year could have been prevented . Conclusion The economic effect of dengue on households , including lost work days , is substantial . The Camino Verde trial intervention reduced household costs for treatment of dengue cases . Trial registration The trial was registered as IS RCT N:27,581,154", "Camino Verde ( the Green Way ) is an evidence -based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases . Its effectiveness was demonstrated in a cluster-r and omised controlled trial conducted in 2010–2013 in Nicaragua and Mexico . The common approach that brought functional consistency to the Camino Verde intervention in both Mexico and Nicaragua is Socialisation of Evidence for Participatory Action (SEPA).In this article , we explain the SEPA concept and its theoretical origins , giving examples of its previous application in different countries and context s. We describe how the approach was used in the Camino Verde intervention , with details that show commonalities and differences in the application of the approach in Mexico and Nicaragua . We discuss issues of cost , replicability and sustainability , and comment on which components of the intervention were most important to its success . In complex interventions , multiple components act in synergy to produce change . Among key factors in the success of Camino Verde were the use of community volunteers called brigadistas , the house-to-house visits they conducted , the use of evidence derived from the communities themselves , and community ownership of the undertaking . Communities received the intervention by r and om assignment ; dengue was not necessarily their greatest concern . The very nature of the dengue threat dictated many of the actions that needed to be taken at household and neighbourhood levels to control it . But within these parameters , communities exercised a large degree of control over the intervention and displayed considerable ingenuity in the process . Trial registration IS RCT N27581154", "Background Underst and ing the breeding patterns of Aedes aegypti in households and the factors associated with infestation are important for implementing vector control . The baseline survey of a cluster r and omised controlled trial of community mobilisation for dengue prevention in Mexico and Nicaragua collected information about the containers that are the main breeding sites , identified possible actions to reduce breeding , and examined factors associated with household infestation . This paper describes findings from the Mexican arm of the baseline survey . Methods In 2010 field teams conducted household surveys and entomological inspections in 11,995 households from 90 representative communities in the three coastal regions of Guerrero State , Mexico . We characterized Ae . aegypti breeding sites and examined the effect of two preventive measures : temephos application in water containers , and keeping the containers covered . We examined associations with household infestation , using bivariate and multivariate analysis adjusted for clustering effects . Results We conducted entomological inspections in 11,995 households . Among 45,353 water containers examined , 6.5 % ( 2958/45,353 ) were positive for larvae and /or pupae . Concrete tanks ( pilas ) and barrels ( tambos ) together accounted for 74 % of pupal productivity . Both covering water containers and inserting temephos were independently associated with a lower risk of presence of larvae or pupae , with the effect of covering ( OR 0.22 ; 95 % CIca 0.15–0.27 ) stronger than that of temephos ( OR 0.66 ; 95 % CIca 0.53–0.84 ) . Having more than four water containers was associated with household infestation in both rural areas ( OR 1.42 ; 95 % CIca 1.17–1.72 ) and urban areas ( 1.81 ; 1.47–2.25 ) , as was low education of the household head ( rural : 1.27 ; 1.11–1.46 , and urban : 1.39 ; 1.17–1.66 ) . Additional factors in rural areas were : household head without paid work ( 1.31 ; 1.08–1.59 ) ; being in the Acapulco region ( 1.91 ; 1.06–3.44 ) ; and using anti-mosquito products ( 1.27 ; 1.09–1.47 ) . In urban areas only , presence of temephos was associated with a lower risk of household infestation ( 0.44 ; 0.32–0.60 ) . Conclusion Concrete tanks and barrels accounted for the majority of pupal productivity . Covering water containers could be an effective means of Ae . aegypti vector control , with a bigger effect than using temephos . These findings were useful in planning and implementing the Camino Verde trial intervention in Mexico", "Camino Verde ( the Green Way ) is an evidence -based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases . Its effectiveness was demonstrated in a cluster-r and omised controlled trial conducted in 2010–2013 in Nicaragua and Mexico . The Nicaraguan arm of the trial was preceded , from 2004 to 2008 , by a feasibility study that provided valuable lessons and trained facilitators for the trial itself . Here , guided by the Template for Intervention Description and Replication ( TIDieR ) , we describe the Camino Verde intervention in Nicaragua , presenting its rationale , its time and location , activities , material s used , the main actors , modes of delivery , how it was tailored to encourage community engagement , modifications made from the feasibility study to the trial itself , and how fidelity to the process originally design ed was maintained . We also present information on costs and discuss the place of this study within the literature on implementation science . Trial registration IS RCT N27581154", "Background Dengue is a serious public health issue that affects households in endemic areas in terms of health and also economically , imposing costs for prevention and treatment of cases . The Camino Verde cluster-r and omised controlled trial in Mexico and Nicaragua assessed the impact of evidence -based community engagement in dengue prevention . The Mexican arm of the trial was conducted in 90 r and omly selected communities in three coastal regions of Guerrero State . This study reports an analysis of a secondary outcome of the trial : household use of and expenditure on anti-mosquito products . We examined whether the education and mobilisation activities of the trial motivated people to spend less on anti-mosquito products . Methods We carried out a household question naire survey in the trial communities in 2010 ( 12,312 households ) and 2012 ( 5349 households in intervention clusters , 5142 households in control clusters ) , including questions about socio-economic status , self-reported dengue illness , and purchase of and expenditure on insecticide anti-mosquito products in the previous month . We examined expenditures on anti-mosquito products at baseline in relation to social vulnerability and we compared use of and expenditures on these products between intervention and control clusters in 2012 . Results In 2010 , 44.2 % of 12,312 households reported using anti-mosquito products , with a mean expenditure of USD4.61 per month among those who used them . Socially vulnerable households spent less on the products . In 2012 , after the intervention , the proportion of households who purchased anti-mosquito products in the last month was significantly lower in intervention clusters ( 47.8 % ; 2503/5293 ) than in control clusters ( 53.3 % ; 2707/5079 ) ( difference − 0.05 , 95 % CIca −0.100 to −0.010 ) . The mean expenditure on the products , among those households who bought them , was USD6.43 ; 30.4 % in the intervention clusters and 36.7 % in the control clusters spent more than this ( difference − 0.06 , 95 % CIca −0.12 to −0.01 ) . These expenditures on anti-mosquito products represent 3.3 % and 3.8 % respectively of monthly household income for the poorest 10 % of the population in 2012 . Conclusions The Camino Verde community mobilisation intervention , as well as being effective in reducing dengue infections , was effective in reducing household use of and expenditure on insecticide anti-mosquito products . Trial registration ( IS RCT N27581154 )", "Background A modified theory of planned behaviour ( acronym CASCADA ) proposes that Conscious knowledge precedes a change in Attitude , which in turn precedes positive deviations from negative Subjective norms , intention to Change , perception of Agency to change , Discussion of possible action , and Action itself . We used this as a results chain to investigate gender-specific behaviour dynamics in chemical-free dengue prevention . Methods Secondary analysis of the Mexican arm of a cluster r and omised controlled trial used household survey data on intermediate outcomes of dengue prevention behaviour . We used a matrix of odds ratios between outcomes , transformed to a symmetrical range ( −1 , 1 ) , to compute fuzzy transitive closure of the results chain for control and intervention clusters , then for male and female respondents separately in each group . Transitive closure of a map computes the influence of each factor on each other factor , taking account of all influences in the system . Cumulative net influence was the sum of influences across the results chain . Results Responses of 5042 women and 1143 men in 45 intervention clusters contrasted with those of 5025 women and 1179 men in 45 control clusters . Control clusters showed a distal block ( negative influence ) in the results chain with a cumulative net influence of 0.88 ; intervention clusters showed no such block and a cumulative net influence of 1.92 . Female control respondents , like the overall control picture , showed a distal block , whereas female intervention responses showed no such blocks ( cumulative net influence 0.78 and 1.73 respectively ) . Male control respondents showed weak distal blocks . Male intervention responses showed several new negative influences and a reduction of cumulative net influence ( 1.38 in control and 1.11 in intervention clusters ) . Conclusions The overall influence of the intervention across the results chain fits with the trial findings , but is different for women and men . Among women , the intervention overcame blocks and increased the cumulative net influence of knowledge on action . Among men , the intervention did not reinforce prevention behaviour . This might be related to emphasis , during the intervention , on women ’s participation and empowerment . The fuzzy transitive closure of the CASCADA map usefully highlights the differences between gender-specific results chains . Trial registration IS RCT N27581154", "Background Studies in different countries have identified irregular water supply as a risk factor for dengue virus transmission . In 2013 , Camino Verde , a cluster-r and omised controlled trial in Managua , Nicaragua , and Mexico ’s Guerrero State , demonstrated impact of evidence -based community mobilisation on recent dengue infection and entomological indexes of infestation by Aedes aegypti mosquitoes . This secondary analysis of data from the trial impact survey asks : ( 1 ) what is the importance of regular water supply in neighbourhoods with and without the trial intervention and ( 2 ) can community interventions like Camino Verde reasonably exclude households with adequate water supply ? Methods Entomological data collected in the dry season of 2013 in intervention and control communities allow contrasts between households with regular and irregular water supplies . Indicators of entomological risk included the House Index and pupa positive household index . Generalised linear mixed models with cluster as a r and om effect compared households with and without regular water , and households in intervention and control communities . Results For the House Index , regular water supply was associated with a protection in both intervention households ( OR 0.7 , 95%CI 0.6–0.9 ) and control households ( OR 0.6 , 95%CI 0.5–0.8 ) . For the pupa positive household index , we found a similar protection from regular water supply in intervention households ( OR 0.6 , 95%CI 0.4–0.8 ) and control households ( OR 0.7 , 95%CI 0.5–0.9 ) . The Camino Verde intervention had a similar impact on House Index in households with regular water supply ( OR 0.7 , 95%CI 0.5–1.0 ) and irregular water supply ( OR 0.6 , 95%CI 0.4–0.8 ) ; for the pupa positive household index , the effect of the intervention was very similar in households with regular ( OR0.5 , 95%CI 0.3–0.8 ) and irregular ( OR 0.5 , 95%CI 0.3–0.9 ) water supply . Conclusion While Aedes aegypti control efforts based on informed community mobilisation had a strong impact on households without a regular water supply , this intervention also impacted entomological indices in households with a regular water supply . These households should not be excluded from community mobilisation efforts to reduce the Aedes aegypti vector . Trial registration IS RCT N27581154", "In conventional r and omised controlled trials ( RCTs ) , research ers design the interventions . In the Camino Verde trial , each intervention community design ed its own programmes to prevent dengue . Instead of fixed actions or menus of activities to choose from , the trial r and omised clusters to a participatory research protocol that began with sharing and discussing evidence from a local survey , going on to local authors hip of the action plan for vector control . Adding equitable stakeholder engagement to RCT infrastructure anchors the research culturally , making it more meaningful to stakeholders . Replicability in other conditions is straightforward , since all intervention clusters used the same engagement protocol to discuss and to mobilize for dengue prevention . The ethical codes associated with RCTs play out differently in community-led pragmatic trials , where communities essentially choose what they want to do . Several discussion groups in each intervention community produced multiple plans for prevention , recognising different time lines . Some chose fast turnarounds , like elimination of breeding sites , and some chose longer term actions like garbage disposal and improving water supplies . A big part of the skill set for community-led trials is being able to st and back and simply support communities in what they want to do and how they want to do it , something that does not come naturally to many vector control programs or to RCT research ers . Unexpected negative outcomes can come from the turbulence implicit in participatory research . One example was the gender dynamic in the Mexican arm of the Camino Verde trial . Strong involvement of women in dengue control activities seems to have discouraged men in setting s where activity in public spaces or outside of the home would ordinarily be considered a “ male competence”.Community-led trials address the tension between one-size-fits-all programme interventions and local needs . Whatever the conventional wisdom about how prevention works at a system level , programmes have to be perceived as locally relevant and they must engage stakeholders who make them work . Locally , each participating community has to know the intervention is relevant to them ; they have to want to do it . That happens much more easily if they design the programme themselves", "Background Temephos in domestic water containers remains a mainstay of Latin American government programmes for control of Aedes aegypti and associated illnesses , including dengue . There is little published evidence about coverage of routine temephos programmes . A cluster r and omised controlled trial of community mobilisation in Mexico and Nicaragua reduced vector indices , dengue infection , and clinical dengue cases . Secondary analysis from the Mexican arm of the trial examined temephos coverage and beliefs , and the impact of the trial on these outcomes . Methods The trial impact survey in December 2012 , in 10,491 households in 45 intervention and 45 control clusters , asked about visits from the temephos programme , retention of applied temephos , and views about temephos and mosquito control . Fieldworkers noted if temephos was present in water containers . Results Some 42.4 % of rural and 20.7 % of urban households reported no temephos programme visits within the last 12 months . Overall , 42.0 % reported they had temephos placed in their water containers less than 3 months previously . Fieldworkers observed temephos in at least one container in 21.1 % of households . Recent temephos application and observed temephos were both significantly more common in urban households , when other household variables were taken into account ; in rural areas , smaller households were more likely to have temephos present . Most households ( 74.4 % ) did not think bathing with water containing temephos carried any health risk . Half ( 51 % ) believed drinking or cooking with such water could be harmful and 17.6 % were unsure . Significantly fewer households in intervention sites ( 16.5 % ) than in control sites ( 26.0 % ) ( Risk Difference − 0.095 , 95 % confidence interval − 0.182 to −0.009 ) had temephos observed in their water ; more households in intervention clusters ( 41.8 % ) than in control clusters ( 31.6 % ) removed the applied temephos quickly . Although fewer households in intervention sites ( 82.7 % ) compared with control sites ( 86.7 % ) ( RD -0.04 , 95 % CI -0.067 to −0.013 ) agreed temephos and fumigation was the best way to avoid mosquitoes , the proportion believing this remained very high . Conclusion Coverage with the government temephos programme was low , especially in rural areas . Despite an intervention encouraging non-chemical mosquito control , most households continued to believe that chemicals are the best control method .Trial registration IS RCT N:27581154", "Background Since the Aedes aegypti mosquitoes that transmit dengue virus can breed in clean water , WHO-endorsed vector control strategies place sachets of organophosphate pesticide , temephos ( Abate ) , in household water storage containers . These and other pesticide-dependent approaches have failed to curb the spread of dengue and multiple dengue virus serotypes continue to spread throughout tropical and subtropical regions worldwide . A feasibility study in Managua , Nicaragua , generated instruments , intervention protocol s , training schedules and impact assessment tools for a cluster r and omised controlled trial of community-based approaches to vector control comprising an alternative strategy for dengue prevention and control in Nicaragua and Mexico . Methods / Design The Camino Verde ( Green Way ) is a pragmatic parallel group trial of pesticide-free dengue vector control , adding effectiveness to the st and ard government dengue control . A r and om sample from the most recent census in three coastal regions of Guerrero state in Mexico will generate 90 study clusters and the equivalent sampling frame in Managua , Nicaragua will generate 60 clusters , making a total of 150 clusters each of 137–140 households . After a baseline study , computer-driven r and omisation will allocate to intervention one half of the sites , stratified by country , evidence of recent dengue virus infection in children aged 3–9 years and , in Nicaragua , level of community organisation . Following a common evidence -based education protocol , each cluster will develop and implement its own collective interventions including house-to-house visits , school-based programmes and inter-community visits . After 18 months , a follow-up study will compare dengue history , serological evidence of recent dengue virus infection ( via measurement of anti-dengue virus antibodies in saliva sample s ) and entomological indices between intervention and control sites . Discussion Our hypothesis is that informed community mobilisation adds effectiveness in controlling dengue . Trial registration IS RCT N27581154", "Background Recent literature on community intervention research stresses system change as a condition for durable impact . This involves highly participatory social processes leading to behavioural change . Methods Before launching the intervention in the Nicaraguan arm of Camino Verde , a cluster-r and omised controlled trial to show that pesticide-free community mobilisation adds effectiveness to conventional dengue controls , we held structured discussion s with leaders of intervention communities on costs of dengue illness and dengue control measures taken by both government and households . These discussion s were the first step in an effort at Socialising Evidence for Participatory Action ( SEPA ) , a community mobilisation method used successfully in other context s. Theoretical grounding came from community psychology and behavioural economics . Results The leaders expressed surprise at how large and unexpected an economic burden dengue places on households . They also acknowledged that large investments of household and government re sources to combat dengue have not had the expected results . Many were not ready to see community preventive measures as a substitute for chemical controls but all the leaders approved the formation of “ brigades ” to promote chemical-free household control efforts in their own communities . Conclusions Discussion s centred on household budget decisions provide a good entry point for research ers to engage with communities , especially when the evidence showed that current expenditures were providing a poor return . People became motivated not only to search for ways to reduce their costs but also to question the current response to the problem in question . This in turn helped create conditions favourable to community mobilisation for change . Trial registration IS RCT N27581154", "Abstract We discuss two ethical issues raised by Camino Verde , a 2011–2012 cluster-r and omised controlled trial in Mexico and Nicaragua , that reduced dengue risk though community mobilisation . The issues arise from the approach adopted by the intervention , one called Socialisation of Evidence for Participatory Action . Community volunteer teams informed householders of evidence about dengue , its costs and the life-cycle of Aedes aegypti mosquitoes , while showing them the mosquito larvae in their own water receptacles , without prescribing solutions . Each community responded in an informed manner but on its own terms . The approach involves partnerships with communities , presenting evidence in a way that brings conflicting views and interests to the surface and encourages communities themselves to deal with the result ing tensions . One such tension is that between individual and community rights . This tension can be resolved creatively in concrete day-to-day circumstances provided those seeking to persuade their neighbours to join in efforts to benefit community health do so in an atmosphere of dialogue and with respect for personal autonomy . A second tension arises between research ers ’ responsibilities for ethical conduct of research and community autonomy in the conduct of an intervention . An ethic of respect for individual and community autonomy must infuse community intervention research from its inception , because as research ers succeed in fostering community self-determination their direct influence in ethical matters diminishes . Trial registration : IS RCT N", "Background A cluster-r and omized controlled trial of community mobilisation for dengue prevention in Mexico and Nicaragua reported , as a secondary finding , a higher risk of dengue virus infection in households where inspectors found temephos in water containers . Data from control sites in the preceding pilot study and the Nicaragua trial arm provided six time points ( 2005 , 2006 , 2007 and 2011 , 2012 , 2013 ) to examine potentially protective effects of temephos on entomological indices under every day conditions of the national vector control programme . Methods Three household entomological indicators for Aedes aegypti breeding were Household Index , Households with pupae , and Pupae per Person . The primary exposure indicator at the six time points was temephos identified physically during the entomological inspection . A stricter criterion for exposure at four time points included households reporting temephos application during the last 30 days and temephos found on inspection . Using generalized linear mixed modelling with cluster as a r and om effect and temephos as a potential fixed effect , at each time point we examined possible determinants of lower entomological indicators . Results Between 2005 and 2013 , temephos exposure was not significantly associated with a reduction in any of the three entomological indices , whether or not the exposure indicator included timing of temephos application . In six of 18 multivariate models at the six time points , temephos exposure was associated with higher entomological indices ; in these models , we could exclude any protective effect of temephos with 95 % confidence . Conclusion Our failure to demonstrate a significant protective association between temephos and entomological indices might be explained by several factors . These include ecological adaptability of the vector , resistance of Aedes to the pesticide , operational deficiencies of vector control programme , or a decrease in preventive actions by households result ing from a false sense of protection fostered by the central ized government programme using chemical agents . Whatever the explanation , the implication is that temephos affords less protection under routine field conditions than expected from its efficacy under experimental conditions . Trial registration IS RCT N 27581154", "Background The follow-up survey of a cluster-r and omised controlled trial of evidence -based community mobilisation for dengue control in Nicaragua and Mexico included entomological information from the 2012 rainy and dry seasons . We used data from the Mexican arm of the trial to assess the impact of the community action on pupal production of the dengue vector Aedes aegypti in both rainy and dry seasons . Methods Trained field workers inspected household water containers in 90 clusters and collected any pupae or larvae present for entomological examination . We calculated indices of pupae per person and pupae per household , and traditional entomological indices of container index , household index and Breteau index , and compared these between rainy and dry seasons and between intervention and control clusters , using a cluster t-test to test significance of differences . Results In 11,933 houses in the rainy season , we inspected 40,323 containers and found 7070 Aedes aegypti pupae . In the dry season , we inspected 43,461 containers and counted 6552 pupae . All pupae and entomological indices were lower in the intervention clusters ( IC ) than in control clusters ( CC ) in both the rainy season ( RS ) and the dry season ( DS ) : pupae per container 0.12 IC and 0.24 CC in RS , and 0.10 IC and 0.20 CC in DS ; pupae per household 0.46 IC and 0.82 CC in RS , and 0.41 IC and 0.83 CC in DS ; pupae per person 0.11 IC and 0.19 CC in RS , and 0.10 IC and 0.20 CC in DS ; household index 16 % IC and 21 % CC in RS , and 12.1 % IC and 17.9 % CC in DS ; container index 7.5 % IC and 11.5 % CC in RS , and 4.6 % IC and 7.1 % CC in DS ; Breteau index 27 % IC and 36 % CC in RS , and 19 % IC and 29 % CC in DS . All differences between the intervention and control clusters were statistically significant , taking into account clustering . Conclusions The trial intervention led to significant decreases in pupal and conventional entomological indices in both rainy and dry seasons . Trial registration IS RCT N27581154", "R and omised controlled trials , when appropriately design ed , conducted , and reported , represent the gold st and ard in evaluating healthcare interventions . However , r and omised trials can yield biased results if they lack method ological rigour [ 1 ] . To assess a trial accurately , readers of a published report need complete , clear , and transparent information on its methodology and findings . Unfortunately , attempted assessment s frequently fail because authors of many trial reports neglect to provide lucid and complete descriptions of that critical information [ 2,3,4 ] . That lack of adequate reporting fuelled the development of the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement in 1996 [ 5 ] and its revision five years later [ 6,7,8 ] . While those statements improved the reporting quality for some r and omised controlled trials [ 9,10 ] , many trial reports still remain inadequate [ 2 ] . Furthermore , new method ological evidence and additional experience has accumulated since the last revision in 2001 . Consequently , we organised a CONSORT Group meeting to up date the 2001 statement [ 6,7,8 ] . We introduce here the result of that process , CONSORT 2010 .", "Background In the Mexican state of Guerrero , some households place fish in water storage containers to prevent the development of mosquito larvae . Studies have shown that larvivorous fish reduce larva count in household water containers , but there is a lack of evidence about whether the use of fish is associated with a reduction in dengue virus infection . We used data from the follow up survey of the Camino Verde cluster r and omised controlled trial of community mobilisation to reduce dengue risk to study this association . Methods The survey in 2012 , among 90 clusters in the three coastal regions of Guerrero State , included a question naire to 10,864 households about socio-demographic factors and self-reported cases of dengue illness in the previous year . Paired saliva sample s provided serological evidence of recent dengue infection among 4856 children aged 3–9 years . An entomological survey in the same households looked for larvae and pupae of Aedes aegypti and recorded presence of fish and temephos in water containers . We examined associations with the two outcomes of recent dengue infection and reported dengue illness in bivariate analysis and then multivariate analysis using generalized linear mixed modelling . Results Some 17 % ( 1730/10,111 ) of households had fish in their water containers . The presence of fish was associated with lower levels of recent dengue virus infection in children aged 3–9 years ( OR 0.64 ; 95 % CI 0.45–0.91 ) , as was living in a rural area ( OR 0.57 ; 95 % CI 0.45–0.71 ) , and being aged 3–5 years ( OR 0.65 ; 95 % CI 0.51–0.83 ) . Factors associated with lower likelihood of self-reported dengue illness were : the presence of fish ( OR 0.79 ; 95 % CI 0.64–0.97 ) , and living in a rural area ( OR 0.74 ; 95 % CI 0.65–0.84 ) . Factors associated with higher likelihood of self-reported dengue illness were : higher education level of the household head ( OR 1.28 ; 95 % CI 1.07–1.52 ) , living in a household with five people or less ( OR 1.33 ; 95 % CI 1.16–1.52 ) and household use of insecticide anti-mosquito products ( OR 1.68 ; 95 % CI 1.47–1.92 ) . Conclusions Our study suggests that fish in water containers may reduce the risk of dengue virus infection and dengue illness . This could be a useful part of interventions to control the Aedes aegypti vector" ]	4118356a-06ff-11f0-808a-c43d1ab1c353
Background Increasing physical activity ( PA ) levels ( regular movement such as walking and activities of daily living ) and reducing time spent sedentary improves cardiovascular health and reduces morbidity and mortality . Fewer than 30 % of independently mobile stroke survivors undertake recommended levels of PA . Sedentary behaviour is also high in this population . We aim ed to systematic ally review the study characteristics and the promise of interventions targeting free-living PA and /or sedentary behaviour in adult stroke survivors . Methods Seven electronic data bases were search ed to identify r and omised controlled trials ( ≥3-months follow-up ) targeting PA and /or sedentary behaviour in adults with first or recurrent stroke or transient ischaemic attack . The quality assessment framework for RCTs was used to assess risk of bias within and across studies . Interventions were rated as “ very ” , “ quite ” or “ non-promising ” based on within- or between-group outcome differences . Intervention descriptions were captured using the TIDieR ( Template for Intervention Description and Replication ) Checklist . Behaviour change techniques ( BCTs ) within interventions were coded using the BCT Taxonomy v1 , and compared between studies by calculating a promise ratio . Results Nine studies fulfilled the review criteria ( N = 717 r and omised stroke patients ) with a high or unclear risk of bias . None of the studies targeted sedentary behaviour . Six studies were very/quite promising ( reported increases in PA post-intervention ) . Studies were heterogeneous in their reporting of participant age , time since stroke , stroke type , and stroke location . Sub-optimal intervention descriptions , treatment fidelity and a lack of st and ardisation of outcome measures were identified . Face to face and telephone-based self-management programmes were identified as having promise to engage stroke survivors in PA behaviour change . Optimal intensity of contact , interventionist type and time after stroke to deliver interventions was unclear . Nine promising BCTs ( ratios ≥2 ) were identified : information about health consequences ; information about social and environmental consequences ; goal setting -behaviour ; problem-solving ; action planning ; feedback on behaviour ; biofeedback ; social support unspecified ; and credible source . Conclusions Future research would benefit from establishing stroke survivor preferences for mode of delivery , setting and intensity , including measurement of physical activity . Interventions need to justify and utilise a theory/model of behaviour change and explore the optimal combination of promising BCTs within interventions	[ "AIM The aim of this study was to determine whether the Comprehensive Reminder System based on the Health Belief Model improves health belief , health behaviours , medication adherence and blood pressure control as a means of decreasing the rate of stroke recurrence among hypertensive ischaemic stroke . BACKGROUND Hypertensive patients having experienced recent ischaemic strokes are at high risk for stroke recurrence . Several trials attempted to improve secondary stroke prevention via patient education , however , patient outcomes remained poor . Long-term follow-up studies regarding secondary stroke prevention are limited . DESIGN A multi-centre , 12-month , assessor-blinded , parallel-group , r and omized controlled longitudinal trial . METHODS Hypertensive patients having experienced an ischaemic stroke are the target population . The intervention consists of health belief education , a calendar h and book , a weekly automated short-message service and four telephone follow-up interviews . Outcomes will be assessed at baseline and at 3 , 6 and 12 months following discharge . The primary outcome is blood pressure control . The secondary outcomes include health belief , health behaviours and medication adherence . The clinical endpoint is the rate of stroke recurrence . DISCUSSION Although many efforts to improve secondary stroke prevention have been undertaken , research indicates that improvements remain possible and warranted . This research protocol based on the Health Belief Model will improve our underst and ing of stroke education and transitional care needed in China and with the world-wide target population", "Objective To assess , in a sample of systematic review s of non-pharmacological interventions , the completeness of intervention reporting , identify the most frequently missing elements , and assess review authors ’ use of and beliefs about providing intervention information . Design Analysis of a r and om sample of systematic review s of non-pharmacological stroke interventions ; online survey of review authors . Data sources and study selection The Cochrane Library and PubMed were search ed for potentially eligible systematic review s and a r and om sample of these assessed for eligibility until 60 ( 30 Cochrane , 30 non-Cochrane ) eligible review s were identified . Data collection In each review , the completeness of the intervention description in each eligible trial ( n=568 ) was assessed by 2 independent raters using the Template for Intervention Description and Replication ( TIDieR ) checklist . All review authors ( n=46 ) were invited to complete a survey . Results Most review s were missing intervention information for the majority of items . The most incompletely described items were : modifications , fidelity , material s , procedure and tailoring ( missing from all interventions in 97 % , 90 % , 88 % , 83 % and 83 % of review s , respectively ) . Items that scored better , but were still incomplete for the majority of review s , were : ‘ when and how much ’ ( in 31 % of review s , adequate for all trials ; in 57 % of review s , adequate for some trials ) ; intervention mode ( in 22 % of review s , adequate for all trials ; in 38 % , adequate for some trials ) ; and location ( in 19 % of review s , adequate for all trials ) . Of the 33 ( 71 % ) authors who responded , 58 % reported having further intervention information but not including it , and 70 % tried to obtain information . Conclusions Most focus on intervention reporting has been directed at trials . Poor intervention reporting in stroke systematic review s is prevalent , compounded by poor trial reporting . Without adequate intervention descriptions , the conduct , usability and interpretation of review s are restricted and therefore , require action by trialists , systematic review ers , peer review ers and editors", "Background and Purpose — Longitudinal conducted studies show that neurologic and functional recovery show faster recovery in the first weeks poststroke . The aim of the present study was to study the effects of progress of time on observed improvements in motor strength , synergisms , and activities during the first 16 weeks poststroke . Methods — Based on data from a previous study , 101 patients with first-ever ischemic middle cerebral artery strokes were prospect ively investigated during the first 16 weeks after stroke . Progress of time was categorized into 8 biweekly time intervals and was used as the independent covariate in a first-order longitudinal regression model . The biweekly time change ( progress of time ) was related to improvement in upper and lower limb motor recovery assessed with Fugl-Meyer score and Motricity Index , reduction in visuospatial inattention based on the letter cancellation task , and improvement in walking ability , dexterity , and activities of daily living measured with the Functional Ambulation Categories , Action Research Arm test , and Barthel Index . Results — Time explained a significant change of 8.4 ( 42 % ) measurement units on the Barthel Index for the first 10 weeks poststroke , 1.1 ( 22 % ) measurement units on Functional Ambulation Categories , and 19 % on the Action Research Arm test for the first 6 and 8 weeks poststroke . Approximately 25 % ( for Fugl-Meyer – arm ) to 26 % ( for Motricity Index – arm ) of the significant change in measurements units was explained by time alone for the upper limb compared with 33 % for Fugl-Meyer – leg and 39 % for Motricity Index – leg of the lower limb . Time accounted for a reduction of 16 % in the letter cancellation task . Observed associations did not change after controlling for covariates such as age , gender , hemisphere of stroke , type of stroke , or intervention . Conclusion — Progress of time is an independent covariate that reflects spontaneous recovery of body functions and activities explaining ≈16 % to 42 % of the observed improvements in the first 6 to 10 weeks after stroke onset", "Background and Purpose — Insulin resistance and glucose intolerance are highly prevalent after stroke , contributing to worsening cardiovascular disease risk and a predisposition to recurrent stroke . Treadmill exercise training ( T-AEX ) increases aerobic capacity ( Vo2 peak ) in chronic stroke patients , suggesting intensity levels that may be adequate to improve glucose metabolism . We compared the effects of a progressive T-AEX intervention to an attention-matched stretching intervention ( CONTROL ) on glucose tolerance and indices of insulin sensitivity in stroke survivors . Methods — Participants had hemiparetic gait after remote ( > 6 months ) ischemic stroke . They were r and omized to 6-month T-AEX or a duration matched reference CONTROL program of supervised stretching exercises . Main outcome measures were glucose and insulin responses during a 3-hour oral glucose tolerance test ( OGTT ) . Results — Forty-six subjects ( T-AEX=26 , CONTROL=20 ) completed OGTT testing before and after the interventions . T-AEX increased Vo2 peak ( + 15 % versus −3 % & Dgr ; , P in fasting insulin ( −23 % versus + 9 % & Dgr ; , P the total integrated 3-hour insulin response ( −24 % versus + 3 % & Dgr ; , P patients with abnormal glucose tolerance at baseline , T-AEX result ed in a significant 14 % decrease in 3-hour glucose response ( n=12 , P of T-AEX participants with abnormal baseline OGTT ( 7 of 12 ) improved glucose tolerance status at 2 hours compared with insulin resistance and prevent diabetes in hemiparetic stroke survivors . Larger clinical trials are needed to definitively establish the use of structured exercise training for stimulating metabolic improvement poststroke", "Even when adults meet physical activity guidelines , sitting for prolonged periods can compromise metabolic health . Television ( TV ) time and objective measurement studies show deleterious associations , and breaking up sedentary time is beneficial . Sitting time , TV time , and time sitting in automobiles increase premature mortality risk . Further evidence from prospect i ve studies , intervention trials , and population -based behavioral studies is required", "BACKGROUND AND PURPOSE Little is known about the relative efficacy of supervised versus unsupervised community exercise programs for stroke survivors . This study compared the effectiveness of a 10-week supervised strengthening and conditioning program ( supervised ) with a 1-week supervised instruction program followed by a 9-week unsupervised home program ( unsupervised ) and evaluated retention of changes at 6 months and 1 year after program completion . METHODS Seventy-two subjects retained at baseline ( 27 women , 45 men ; mean+/-SD age , 64.6+/-11.8 years ) were r and omly allocated to receive the supervised or unsupervised program . The primary outcome was walking speed over 6 minutes , and secondary outcome measures were Human Activity Profile , Medical Outcome Study 36-Item Short-Form survey ( SF-36 ) , Physiological Cost Index , and lower extremity muscle strength . RESULTS The 6-minute walking speed increased significantly in both groups and remained significantly improved by 1 year . The Human Activity Profile demonstrated an increasing trend only in the supervised group that was significant by 1 year . The SF-36 Physical Component summary score increased significantly in the supervised group and remained improved by 1 year ; the unsupervised group showed significant improvement at 1 year . Women made greater gains in supervised programs , but men made greater gains in unsupervised programs . CONCLUSIONS Supervised exercise programs and unsupervised programs after initial supervised instruction were both associated with physical benefits that were retained for 1 year , although supervised programs showed trends to greater improvements in self-reported gains . Gender differences require further research", "Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours . We aim ed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement , perceived usefulness , behavior change and program delivery preferences . Methods Mixed methods qualitative design combining four data sources ; ( i ) analytic data extracted directly from the software system , ( ii ) participant survey , ( iii ) focus groups to identify barriers and enablers to implementation and mechanisms of effect and ( iv ) recruitment screening logs and text message responses to examine engagement . This evaluation was conducted within the TEXT ME trial — a parallel design , single-blind r and omized controlled trial ( RCT ) of 710 patients with coronary heart disease ( CHD ) . Qualitative data were interpreted using inductive thematic analysis . Results 307/352 ( 87 % response rate ) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group . Factors increasing engagement included ( i ) ability to save and share messages , ( ii ) having the support of providers and family , ( iii ) a feeling of support through participation in the program , ( iv ) the program being initiated close to the time of a cardiovascular event , ( v ) personalization of the messages , ( vi ) opportunity for initial face-to-face contact with a provider and ( vii ) that program and content was perceived to be from a credible source . Clear themes relating to program delivery were that diet and physical activity messages were most valued , four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer . Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aim ed at improving health-related behavior . The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling . Trial Registration Australia and New Zeal and Clinical Trials Registry , ACTRN12611000161921", "Background Physical activity ( PA ) and nutrition are the cornerstones of diabetes management . Several review s and meta-analyses report that PA independently produces clinical ly important improvements in glucose control in people with Type 2 diabetes . However , it remains unclear what the optimal strategies are to increase PA behaviour in people with Type 2 diabetes in routine primary care . Methods This study will determine whether an evidence -informed multifaceted behaviour change intervention ( Movement as Medicine for Type 2 Diabetes ) targeting both consultation behaviour of primary healthcare professionals and PA behaviour in adults with Type 2 diabetes is both acceptable and feasible in the primary care setting . An open pilot study conducted in two primary care practice s ( phase one ) will assess acceptability , feasibility and fidelity . Ongoing feedback from participating primary healthcare professionals and patients will provide opportunities for systematic adaptation and refinement of the intervention and study procedures . A two-arm parallel group clustered pilot r and omised controlled trial with patients from participating primary care practice s in North East Engl and will assess acceptability , feasibility , and fidelity of the intervention ( versus usual clinical care ) and trial processes over a 12-month period . Consultation behaviour involving fidelity of intervention delivery , diabetes and PA related knowledge , attitudes/beliefs , intentions and self-efficacy for delivering a behaviour change intervention targeting PA behaviour will be assessed in primary healthcare professionals . We will rehearse the collection of outcome data ( with the focus on data yield and quality ) for a future definitive trial , through outcome assessment at baseline , one , six and twelve months . An embedded qualitative process evaluation and treatment fidelity assessment will explore issues around intervention implementation and assess whether intervention components can be reliably and faithfully delivered in routine primary care . Discussion Movement as Medicine for Type 2 Diabetes will address an important gap in the evidence -base , that is , the need for interventions to increase free-living PA behaviour in adults with Type 2 diabetes . The multifaceted intervention incorporates an online accredited training programme for primary healthcare professionals and represents , to the best of our knowledge , the first of its kind in the United Kingdom . This study will establish whether the multifaceted behavioural intervention is acceptable and feasible in routine primary care . Trial registration Movement as Medicine for Type 2 Diabetes ( MaMT2D ) was registered with Current Controlled Trials on the 14th January 2012 : IS RCT N67997502 . The first primary care practice was r and omised on the 5th October 2012", "Objective The aim of this study was to directly compare the effects of aerobic training ( AT ) with progressive resistance training ( RT ) after stroke to determine whether AT-induced fitness gains or RT-induced strength gains translate into improved ambulation across a 12-wk intervention and whether gains are retained 1 yr after cessation of formal training . Design This study is a r and omized controlled 12-wk intervention trial with a 1-yr follow-up . Forty-three community-dwelling independent walkers with a chronic ischemic hemiparetic stroke were allocated to AT using a cycle ergometer ( n = 13 ) , RT using training machines ( n = 14 ) , or low-intensity sham training of the arms ( n = 16 ) . The main outcome measures were 6-min walk distance and fast 10-m walking speed . Results Comparisons between AT , RT , and sham training revealed no clinical ly relevant effects on walking velocity or walking distance . Muscle strength improved after RT ( P Aerobic capacity increased after AT ( P muscle strength or aerobic capacity using non – task-specific training methods does not result in improved ambulation in patients with chronic stroke . Muscle strength gains were maintained at follow-up , whereas all improvements of aerobic capacity were lost , indicating a long-lasting effect of intensive RT even without maintenance training", "The purpose of this study is to evaluate the effects of targeting both the motivation and action phases of behaviour change in a 5-week intervention to increase physical activity ( PA ) among patients with rheumatoid arthritis ( RA ) not meeting current PA recommendations . In a r and omised controlled trial , a control group — which received a group-based patient education session led by a physical therapist — was compared to a treatment group which received the education session plus a motivational interview from a physical therapist and two self-regulation coaching sessions from a rheumatology nurse . Outcomes included leisure-time PA , days per week with at least 30 min of moderate-intensity PA , self-efficacy and autonomous motivation ( cognitions which predict PA initiation and maintenance ) , disease activity , functional status , depressive symptoms and fatigue . Effects were assessed using mixed models repeated measures . Of the 78 patients r and omised , 76 and 67 completed the post-treatment and follow-up assessment s , respectively . Significant treatment effects were found for leisure-time PA ( p = 0.022 ) , active days/week ( p = 0.016 ) , self-efficacy ( p = 0.008 ) and autonomous motivation ( p = 0.001 ) . At post-treatment and 6-months follow-up , significantly more treated patients than controls met current PA recommendations . No significant effects were found for disease activity , functional status , depressive symptoms or fatigue . Combining motivation- and action-focused intervention approaches improved PA-related cognitions and led to improved uptake and maintenance of leisure-time PA . However , further research is necessary to identify ways of helping patients with RA transition to— and maintain — more intensive forms of PA which are more likely to improve disease activity and functional status", "PURPOSE Development and validation of a physical activity scale for measuring physical activity in 24 h of sports , work , and leisure time on an average weekday . METHODS For development of the physical activity scale , 2500 r and omly selected Danish men and women between the age of 20 and 60 were contacted by mail and asked to select frequent and relevant physical activities from a number of activities of known MET intensity . The activities were included in the physical activity scale , organized in nine different MET levels ranging from sleep/rest ( 0.9 METs ) to high-intensity physical activities ( > 6 METs ) . Face validity of the physical activity scale was explored through interviews with 10 volunteer men and women . Concurrent validity was assessed against 4 d of accelerometry ( CSA 7164 ) and physical activity diary in 40 volunteer men and women between 20 and 60 yr of age . RESULTS The correlation between the activity scale and the diary was high ( r = 0.74 , P = 0.000 ) , whereas correlation between the activity scale and accelerometer measurements was poor ( r = 0.20 , NS ) . The physical activity scale MET-time was systematic ally higher than average MET-time estimated from the diary , and the difference increased with increasing total MET-time . CONCLUSION The physical activity scale appears to be a simple and valid alternative to measuring physical activity by diary in adult sedentary to moderately active Danes . The scale encompasses work , leisure time , and sports activity in one measure ; it is easy to administer , and it provides detailed information on different activity levels as well as a single measure of the total amount of physical activity on an average weekday", "ABSTRACT Secondary stroke prevention is championed as guideline care ; yet there are no systematic programs offered . We developed a stroke self-management program to address this gap and pilot test the program . We conducted a r and omized controlled trial at two Veterans Administration ( VA ) hospital sites where we recruited patients with an acute stroke to receive either the stroke program or an attention-control protocol over a 12-week period following hospital discharge . The stroke program included six sessions that facilitated stroke self management focusing on increasing self-efficacy to recover from stroke and engage in secondary stroke risk factor management . We surveyed outcomes at baseline , 3 and 6 months . We conducted an intention to treat analysis comparing the intervention to the control group on changes of outcomes between baseline and follow-up modeled by a linear model with fixed effects for treatment , visit , and the treatment by visit interaction adjusting for baseline . We recruited 63 participants ( 33 control and 30 intervention ) who were hospitalized with a primary diagnosis of ischemic stroke . We found trends in differences between groups on self-efficacy to communicate with physicians , weekly minutes spent in aerobic exercise , and on dimensions of stroke-specific quality of life . This pilot study demonstrated the feasibility of delivering a stroke self-management program to recent stroke survivors in a healthcare organization . The program also demonstrated improvements in patient self-efficacy , self-management behaviors , specific dimensions of stroke-specific quality of life compared to a group that received an attention placebo program", "UNLABELLED Mudge S , Barber PA , Stott NS . Circuit-based rehabilitation improves gait endurance but not usual walking activity in chronic stroke : a r and omized controlled trial . OBJECTIVE To determine whether circuit-based rehabilitation would increase the amount and rate that individuals with stroke walk in their usual environments . DESIGN Single-blind r and omized controlled trial . SETTING Rehabilitation clinic . PARTICIPANTS Sixty participants with a residual gait deficit at least 6 months after stroke originally enrolled in the study . Two withdrew in the initial phase , leaving 58 participants ( median age , 71.5y ; range , 39.0 - 89.0y ) who were r and omized to the 2 intervention groups . INTERVENTIONS The exercise group had 12 sessions of clinic-based rehabilitation delivered in a circuit class design ed to improve walking . The control group received a comparable duration of group social and educational classes . MAIN OUTCOME MEASURES Usual walking performance was assessed using the StepWatch Activity Monitor . Clinical tests were gait speed ( timed 10-meter walk ) and endurance ( six-minute walk test [ 6MWT ] ) , confidence ( Activities-Based Confidence Scale ) , self-reported mobility ( Rivermead Mobility Index [ RMI ] ) , and self-reported physical activity ( Physical Activity and Disability Scale ) . RESULTS Intention-to-treat analysis revealed that the exercise group showed a significantly greater distance for the 6MWT than the control group immediately after the intervention ( P=.030 ) but that this effect was not retained 3 months later . There were no changes in the StepWatch measures of usual walking performance for either group . The exercise and control groups had significantly different gait speed ( P=.038 ) and scores on the RMI ( P=.025 ) at the 3-month follow-up . These differences represented a greater decline in the control group compared with the exercise group for both outcome measures . CONCLUSIONS Circuit-based rehabilitation leads to improvements in gait endurance but does not change the amount or rate of walking performance in usual environments . Clinical gains made by the exercise group were lost 3 months later . Future studies should consider whether rehabilitation needs to occur in usual environments to improve walking performance ", "Background and Purpose : Transient ischemic attack ( TIA ) is a strong predictor of stroke , and physical inactivity is one risk factor for TIA/stroke . “ Physical activity on Prescription ” ( PaP ) can increase physical activity , but the effect of PaP after TIA has not been described . Our goal was to objective ly measure the effect of PaP on physical activity and physical capacity , as well as self-rated health at 3 and 6 months after TIA . Methods : The primary outcome was moderate to vigorous intensities of physical activity objective ly assessed by accelerometry . Secondary outcomes were steps per day assessed by accelerometry , physical capacity assessed by the 6-minute walk test , and self-rated health assessed by EQ-5D VAS . Results : Eighty-eight individuals with TIA were r and omized to an intervention group ( n = 44 ) that received conventional treatment and PaP or to a control group ( n = 44 ) that received conventional treatment alone . There was a 30 % dropout among the participants at 6 months . No significant differences between groups were found in physical activity at 3 and 6 months . At 6 months , participants in the intervention group were significantly more likely to have improved their physical capacity than the control group . There was no significant difference between groups in self-rated health . Discussion and Conclusions : PaP did not increase physical activity after TIA ; however , there was an increase in physical capacity . The nonsignificant results for physical activity may be the result of a relatively high baseline physical activity level . The results may also indicate that prior studies suggesting that PaP increases physical activity overestimated effects because of the self-reported nature of the previous outcomes . Video Abstract available for more insights from the authors ( see Supplemental Digital Content 1 , http://links.lww.com/JNPT/A134 )", "OBJECTIVE To test the safety , feasibility , and effectiveness of reducing sitting time in stroke survivors . DESIGN R and omized controlled trial with attention-matched controls and blinded assessment s. SETTING Community . PARTICIPANTS Stroke survivors ( N=35 ; 22 men ; mean age , 66.9±12.7y ) . INTERVENTIONS Four counseling sessions over 7 weeks with a message of sit less and move more ( intervention group ) or calcium for bone health ( attention-matched control group ) . MAIN OUTCOME MEASURES Measures included safety ( adverse events , increases in pain , spasticity , or fatigue ) and feasibility ( adherence to trial protocol ) . Secondary measures included time spent sitting ( including in prolonged bouts ≥30min ) , st and ing , and stepping as measured by the thigh-worn inclinometer ( 7d , 24h/d protocol ) and time spent in physical activity of at least moderate intensity as measured by a triaxial accelerometer . The Multimedia Activity Recall for Children and Adults was used to describe changes in use of time . RESULTS Thirty-three participants completed the full protocol . Four participants reported falls during the intervention period with no other adverse events . From a baseline average of 640.7±99.6min/d , daily sitting time reduced on average by 30±50.6min/d ( 95 % confidence interval [ CI ] , 5.8 - 54.6 ) in the intervention group and 40.4±92.5min/d in the control group ( 95 % CI , 13.0 - 93.8 ) . Participants in both groups also reduced their time spent in prolonged sitting bouts ( ≥30min ) and increased time spent st and ing and stepping . CONCLUSIONS Our protocol was both safe and feasible . Participants in both groups spent less time sitting and more time st and ing and stepping postintervention , but outcomes were not superior for intervention participants . Attention matching is desirable in clinical trials and may have contributed to the positive outcomes for control participants", "Objective : To investigate whether early aerobic training has a beneficial effect on stroke patients ' independence in daily and social activities six months after the event . Design : R and omized clinical trial . Setting : Rehabilitation unit . Subjects : Ninety-two patients after a first stroke . Interventions : Forty-six patients participated in an eight-week programme of aerobic training , using a leg cycle ergometer . Main outcome measures : Frenchay Activities Index ( FAI ) measured twice , at entry to programme ( pre-event score ) and six months after the onset of the event . Results : Despite the significant improvement of study group patients ' functional abilities immediately after the intervention compared with controls , no significant difference was found in FAI mean score between groups six months post event . An interaction effect was noted between event severity , intervention and FAI total score . Mean FAI score declined significantly less in the less severely impaired study group patients . Conclusions : Early , moderately intense aerobic training has no direct impact on independence in daily and social activities as measured by FAI total score six months after a stroke", "This investigation compared ratings of perceived exertion specific to the active muscles used during resistance exercise ( RPE-AM ) using the 15-category Borg scale during high-intensity ( HIP ) and low-intensity ( LIP ) weight lifting . Ten men ( 23.2 ± 3.6 years ) and 10 women ( 21.8 ± 2.7 years ) performed 2 trials consisting of seven exercises : bench press ( BP ) , leg press , latissimus dorsi pull down , triceps press , biceps curl , shoulder press , and calf raise . The HIP and LIP protocol s were completed in counterbalanced order . During HIP , subjects completed 5 repetitions using 90 % of 1 repetition maximum ( 1RM ) . RPE-AM was measured after every repetition . During LIP , subjects completed 15 repetitions using 30 % of 1RM . RPE-AM was measured after every third repetition . RPE-AMs were greater ( p example , the mean initial BP RPE was 14.11 ± 2.08 for the HIP and 8.34 ± 1.35 for the LIP . Performing few repetitions using heavier weight is perceived to be more difficult than lifting comparatively lighter weight with more repetitions when external work is held constant", "Abstract Background : Many people with mild disability after stroke are physically inactive despite the risk of recurrent stroke . A self-management program may be one strategy to increase physical activity in stroke survivors . Objectives : To investigate the feasibility of a self-management program , and determine whether self-management can increase daily physical activity levels and self-efficacy for exercise , decrease cardiovascular risk , and improve walking ability , participation , and quality of life in people with mild disability after stroke . Method : A Phase I , single-group , pre-post intervention study was carried out with twenty stroke survivors who had mild disability and were discharged directly home from acute stroke units . A self-management program was delivered via five home-based sessions over 3 months , incorporating : education , goal setting , barrier identification , self-monitoring , and feedback . Feasibility of the intervention was determined by examining adherence , duration , usefulness , and safety . Clinical outcomes were amount of physical activity ( duration of moderate physical activity in min/day and counts of physical activity in steps/day ) , self-efficacy , cardiovascular risk , walking ability , participation , and quality of life . Results : The intervention was feasible with 96 % of sessions being delivered , each taking less than an hour ( 41 min , SD 12 ) . Participants perceived the self-management program to be useful and there were few adverse events . At 3 months , participants completed 27 min/day ( 95 % CI 4–49 ) more moderate physical activity than at baseline and 16 min/day ( 95 % CI −10 to 42 ) at 6 months . Conclusion : Self-management appears to be feasible and has the potential to increase physical activity in people with mild disability after stroke . A Phase II r and omized trial is warranted" ]	411835e2-06ff-11f0-808a-c43d1ab1c353
The aim of this systematic review was to determine whether there is a root canal filling for deciduous teeth equally or more effective than zinc oxide-eugenol cement ( ZOE ) . Six clinical trials selected for inclusion were independently review ed by two research ers . Only two showed statistically significant different success rates between the test and the control groups . One found that an iodoform paste with calcium hydroxide ( IP + Ca ) performed better than ZOE , and the other found that ZOE performed similarly to IP + Ca . The other four studies compared ZOE with an iodoform paste ( IP ) , a calcium hydroxide cement ( Ca(OH)(2 ) ) , or IP + Ca . In these trials , the success rates in the ZOE groups were slightly lower than in the other groups . There seems to be no convincing evidence to support the superiority of any material over ZOE , and both ZOE and IP + Ca appear to be suitable as root canal fillings for deciduous teeth	[ "To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results", "PURPOSE The purpose of this study was to compare clinical and radiographic success rates of zinc oxide-eugenol cement ( ZOE ) vs calcium hydroxide/iodoform paste ( Vitapex ) in pulpectomized primary molars at 6 and 12 months . METHODS Fifty-four m and ibular primary molars from 42 children ( average age 5.6 + /- 1.2 years ) that met the inclusion criteria were allocated to either test material via block r and omization . A 1-visit pulpectomy and stainless steel crown was performed by 1 investigator . The clinical and radiographic diagnoses were blindly assessed by another investigator with an intraexaminer reliability of 0.85 to 0.95 ( kappa value ) . RESULTS At 6 and 12 months , the ZOE success rates were 48 % and 85 % , respectively , and the Vitopex success rates were 78 % and 89 % . The difference in success rates between material s at 6 months was statistically significant , but at 12 months it was not . CONCLUSIONS Vitapex appeared to resolve furcation pathology at a foster rate than zinc oxide-eugenol at 6 months , while at 12 months , both material s yielded similar results", "Calcium hydroxide , a material widely used for the treatment of permanent teeth has not been used frequently for pulpectomy in primary teeth . A comparative evaluation of calcium hydroxide and zinc oxide eugenol used as root canal filling material s in primary molars is presented", "The present study , performed in-vivo , included 30 infected primary teeth in 26 children in the age group of 3 - 8 years . The purpose of this study was to compare the efficacy of two obturating material s , zinc oxide-eugenol and Maisto 's paste , in infected primary teeth . 30 teeth were divided into two groups of 15 teeth . Teeth in Group I were obturated using zinc oxide-eugenol and those in Group II were obturated using Maisto 's paste . On clinical evaluation , teeth obturated with Maisto 's paste showed 100 % success . Five teeth that were overfilled with Maisto 's paste showed complete resorption of excess material within 3 months while the two teeth overfilled with zinc oxide-eugenol showed incomplete resorption of the excess material even after 9 months . Zinc oxide-eugenol treated cases showed only 26.7 % bone regeneration while in case of Maisto 's paste , it was 93 % . Complete healing of the inter-radicular pathology was seen with Maisto 's paste . However , the pathology was present in 40 % of the zinc oxide-eugenol treated teeth even after 9 months . Maisto 's paste was thus seen to be superior to zinc oxide-eugenol both in clinical as well as radiological evaluation , done over a period of 9 months in relation to bone regeneration , healing of inter-radicular pathology and resorption of excess material", "PURPOSE To evaluate the clinical and radiographic success of zinc oxide-eugenol ( ZOE ) , Calcicur , Sealapex and Vitapex in primary molar pulpectomies . METHODS 80 primary molars , showing signs of pulpal and /or periapical involvement , with no abnormal mobility , were selected from 76 children aged between 4 - 9 years-old , free from systemic disease . Radiographic evaluation was done to exclude teeth showing internal or pathological external root resorption and /or inadequate bone support . The selected teeth ( 20 in each group ) were r and omly treated with ZOE , Sealapex , Calcicur and Vitapex . The procedure involved primarily a one-visit pulpectomy . The teeth were evaluated clinical ly and radiographically every 2 months for a period of 18 months . RESULTS In the ZOE group , all pulpectomies were successful . In the Sealapex group , two pulpectomies and in the Calcicur group , four pulpectomies showed complete resorption of the material in the root canal . Although re-treatment was performed , those teeth had to be removed due to pathological root resorption . In the Vitapex group , although six pulpectomies showed resorption of the filling material within the canals , this had no effect on the clinical and radiographical success of the treatment", "Endodontic treatment was performed on 25 pulpally involved m and ibular primary molars in 4 to 9-year-old children ; the root canals were obturated with a new root canal filling material consisting of a mixture of calcium hydroxide , zinc oxide , and 10 % sodium fluoride solution , using h and -operated lentulo-spirals . All cases were evaluated clinical ly every 3 months and also radiographically every 6 months to assess the success of the treatment ; we also examined the resorption of the root canal filling material from the root canals and the status of overpushed material , if any , as the tooth resorbed with the passage of time . At 6 months , endodontic treatment in 2 of the 25 teeth had failed and one tooth had exfoliated ; the remaining 22 teeth were without any signs or symptoms . At the end of 2 years , 14 teeth could be evaluated ; out of these 12 had physiologically exfoliated . It was observed that the rate of resorption of this new root canal obturating mixture was quite similar to the rate of physiologic root resorption in primary teeth . In three cases , where there was an overpush of the mixture , a gradual partial resorption was noted", " OBJECTIVES The aims of this study were to evaluate iodoform base material s for root canal treatment of necrotic primary teeth , and to compare them with traditionally used zinc oxide and eugenol ( ZOE ) . SAMPLE AND METHODS Zinc oxide and eugenol and Vitapex ( a premixed calcium hydroxide and iodoform paste ) were compared for root canal treatment in 52 necrotic primary teeth in two groups of children with a mean age of 5 years and 8.4 months . All the patients were followed-up clinical ly and radiographically 3 months and 10 - 16 months postoperatively . RESULTS The overall success rates of Vitapex and ZOE were 100 % and 78.5 % , respectively . Using Fisher 's Exact Test , the difference was statistically significant ( P ZOE and Vitapex gave encouraging results . Vitapex , however , can be used more safely whenever there is a doubt about the patient 's return for follow-up" ]	4118365a-06ff-11f0-808a-c43d1ab1c353
Background Governments use different approaches to ensure that private for‐profit healthcare services meet certain quality st and ards . Such government guidance , referred to as public stewardship , encompasses government policies , regulatory mechanisms , and implementation strategies for ensuring accountability in the delivery of services . However , the effectiveness of these strategies in low‐ and middle‐income countries ( LMICs ) have not been the subject of a systematic review . Objectives To assess the effects of public sector regulation , training , or co‐ordination of the private for‐profit health sector in low‐ and middle‐income countries . Search methods For related systematic review s , we search ed the Cochrane Data base of Systematic Review s ( CDSR ) 2015 , Issue 4 ; Data base of Abstract s of Review s of Effectiveness ( DARE ) 2015 , Issue 1 ; Health Technology Assessment Data base ( HTA ) 2015 , Issue 1 ; all part of The Cochrane Library , and search ed 28 April 2015 . For primary studies , we search ed MEDLINE , Epub Ahead of Print , In‐Process & Other Non‐Indexed Citations , MEDLINE Daily and MEDLINE 1946 to Present , OvidSP ( search ed 16 June 2016 ) ; Science Citation Index and Social Sciences Citation Index 1987 to present , and Emerging Sources Citation Index 2015 to present , ISI Web of Science ( search ed 3 May 2016 for papers citing included studies ) ; Cochrane Central Register of Controlled Trials ( CENTRAL ) , 2015 , Issue 3 , part of The Cochrane Library ( including the Cochrane Effective Practice and Organisation of Care ( EPOC ) Group Specialised Register ) ( search ed 28 April 2015 ) ; Embase 1980 to 2015 Week 17 , OvidSP ( search ed 28 April 2015 ) ; Global Health 1973 to 2015 Week 16 , OvidSP ( search ed 30 April 2015 ) ; WHOLIS , WHO ( search ed 30 April 2015 ) ; Science Citation Index and Social Sciences Citation Index 1975 to present , ISI Web of Science ( search ed 30 April 2015 ) ; Health Management , ProQuest ( search ed 22 November 2013 ) . In addition , in April 2016 , we search ed the reference lists of relevant articles , WHO International Clinical Trials Registry Platform , Clinical trials.gov , and various electronic data bases of grey literature . Selection criteria R and omised trials , non‐r and omised trials , interrupted time series studies , or controlled before‐after studies . Data collection and analysis Two authors independently assessed study eligibility and extracted data , comparing their results and resolving discrepancies by consensus . We expressed study results as risk ratios ( RR ) or mean differences ( MD ) with 95 % confidence intervals ( CI ) , where appropriate , and assessed the certainty of the evidence using Grade s of Recommendation , Assessment , Development and Evaluation ( GRADE ) . We did not conduct meta‐ analysis because of heterogeneity of interventions and study design s. Main results We identified 20,177 records , 50 of them potentially eligible . We excluded 39 potentially eligible studies because they did not involve a rigorous evaluation of training , regulation , or co‐ordination of private for‐profit healthcare providers in LMICs ; five studies identified after the review was su bmi tted are awaiting assessment ; and six studies met our inclusion criteria . Two included studies assessed training alone ; one assessed regulation alone ; three assessed a multifaceted intervention involving training and regulation ; and none assessed co‐ordination . All six included studies targeted private for‐profit pharmacy workers in Africa and Asia . Three studies found that training probably increases sale of oral rehydration solution ( one trial in Kenya , 106 pharmacies : RR 3.04 , 95 % CI 1.37 to 6.75 ; and one trial in Indonesia , 87 pharmacies : RR 1.41 , 95 % CI 1.03 to 1.93 ) and dispensing of anti‐malarial drugs ( one trial in Kenya , 293 pharmacies : RR 8.76 , 95 % CI 0.94 to 81.81 ) ; moderate‐certainty evidence . One study conducted in the Lao People 's Democratic Republic shows that regulation of the distribution and sale of registered pharmaceutical products may improve composite pharmacy indicators ( one trial , 115 pharmacies : improvements in four of six pharmacy indicators ; low‐certainty evidence ) . The outcome in three multifaceted intervention studies was the quality of pharmacy practice ; including the ability to ask questions , give advice , and provide appropriate treatment . The trials applied regulation , training , and peer influence in sequence ; and the study design does not permit separation of the effects of the different interventions . Two trials conducted among 136 pharmacies in Vietnam found that the multifaceted intervention may improve the quality of pharmacy practice ; but the third study , involving 146 pharmacies in Vietnam and Thail and , found that the intervention may have little or no effects on the quality of pharmacy practice ( low‐certainty evidence ) . Only two studies ( both conducted in Vietnam ) reported cost data , with no rigorous assessment of the economic implication s of implementing the interventions in re source ‐constrained setting s. No study reported data on equity , mortality , morbidity , adverse effects , satisfaction , or attitudes . Authors ' conclusions Training probably improves quality of care ( i.e. adherence to recommended practice ) , regulation may improve quality of care , and we are uncertain about the effects of co‐ordination on quality of private for‐profit healthcare services in LMICs . The likelihood that further research will find the effect of training to be substantially different from the results of this review is moderate ; implying that monitoring of the impact is likely to be needed if training is implemented . The low certainty of the evidence for regulation implies that the likelihood of further research finding the effect of regulation to be substantially different from the results of this review is high . Therefore , an impact evaluation is warranted if government regulation of private for‐profit providers is implemented in LMICs . Rigorous evaluations of these interventions should also assess other outcomes such as impacts on equity , cost implication s , mortality , morbidity , and adverse effects	[ "OBJECTIVES The objective of this study was to assess the effectiveness of government regulation of private pharmacy practice in a low-income country . METHODS The intervention comprised inspections of the pharmacies , information , and distribution of documents to drug sellers and sanctions . It was implemented at two different intensity levels , active and regular intervention . The methods used to assess the effect of the interventions were interviews with the district drug inspectors , drug sellers and customers , inspection of drug purchases , and indicator surveys of pharmacies . Indicators for pharmacy-specific quality as well as for dispensing quality were developed . RESULTS The main finding was one of strong overall improvements from initially low levels . The improvements were particularly marked by increases in the availability of essential material s for dispensing by 34 % and in order in the pharmacy by 19 % . Information given to customers increased from 35 % to 51 % and the mixing of different drugs in the same package went down from 17 % to 9 % . The pharmacies in the active intervention districts showed greater improvements for four of the six indicators , although statistically significant compared with the regular intervention districts only for the essential material s indicator . CONCLUSIONS It was concluded that the regulatory activities have probably been an important factor behind the service quality improvements . It appeared feasible as well as effective to regulate private pharmacy practice in this particular low-income setting", "OBJECTIVE The study was carried out to evaluate short term effects of one to one educational intervention approach , conducted with 40 drug sellers in order to improve the private sector 's practice s , compliance and performance in using the national treatment guidelines for malaria and other common childhood ( diarrhoea , acute respiratory tract infection-ARI ) illnesses in Kibaha district-Tanzania . METHODS The training took place one month after baseline data collection . Data collection was undertaken eight months after training and the effects of training was evaluated . The 40 drug stores were divided into 20 intervention and 20 control facilities . Trained nurses were used as clients who posed as caretakers of sick under-five children needing medication . The drug dispensers/sellers knowledge of anti-malarials and other drugs and their dispensing practice s was assessed . RESULTS The intervention seemed to have had a significant impact on knowledge pattern for prescribing and dispensing practice s of drug stores for some common childhood illnesses but not in other control drug stores/shops . About 90 % ( n=18 ) of shops prescribed to clients , the approved first-line anti-malarial drug for uncomplicated malaria ( sulfadoxine-pyrimethamine ) , as compared to only 55 % ( n=11 ) of the control shops . CONCLUSION Changing the private sectors ' knowledge , behaviour and practice s/performance may be a slow and difficult process . The intervention approach applied in this study seems to be feasible at district-level . This strategy can be applied in all districts of Tanzania with the aim of achieving significant improvements in knowledge , behaviour , compliance , improving performance and practice s of drug sellers in drug stores/shops . However , other alternative strategies are needed to influence drug sellers'/dispensers ' compliance and performance . Thus , the overall impact on performance and practice s in these facilities will remain at moderate level for quite sometime unless national policies , other programs and stakeholders are involved actively", "Background Pneumonia is a leading cause of death among children under five years of age . The Integrated Management of Childhood Illness strategy can improve the quality of care for pneumonia and other common illnesses in developing countries , but adherence to these guidelines could be improved . We evaluated an intervention in Benin to support health worker adherence to the guidelines after training , focusing on pneumonia case management . Methods We conducted a r and omized trial . After a health facility survey in 1999 to assess health care quality before Integrated Management of Childhood Illness training , health workers received training plus either study supports ( job aids , non-financial incentives and supervision of workers and supervisors ) or \" usual \" supports . Follow-up surveys were conducted in 2001 , 2002 and 2004 . Outcomes were indicators of health care quality for Integrated Management-defined pneumonia . Further analyses included a graphical pathway analysis and multivariable logistic regression modelling to identify factors influencing case-management quality . Results We observed 301 consultations of children with non-severe pneumonia that were performed by 128 health workers in 88 public and private health facilities . Although outcomes improved in both intervention and control groups , we found no statistically significant difference between groups . However , training proceeded slowly , and low- quality care from untrained health workers diluted intervention effects . Per- protocol analyses suggested that health workers with training plus study supports performed better than those with training plus usual supports ( 20.4 and 19.2 percentage-point improvements for recommended treatment [ p = 0.08 ] and \" recommended or adequate \" treatment [ p = 0.01 ] , respectively ) . Both groups tended to perform better than untrained health workers . Analyses of treatment errors revealed that incomplete assessment and difficulties processing clinical findings led to missed pneumonia diagnoses , and missed diagnoses led to inadequate treatment . Increased supervision frequency was associated with better care ( odds ratio for recommended treatment = 2.1 [ 95 % confidence interval : 1.1 - 3.9 ] per additional supervisory visit ) . Conclusion Integrated Management of Childhood Illness training was useful , but insufficient , to achieve high- quality pneumonia case management . Our study supports led to additional improvements , although large gaps in performance still remained . A simple graphical pathway analysis can identify specific , common errors that health workers make in the case-management process ; this information could be used to target quality improvement activities , such as supervision ( Clinical Trials.gov number NCT00510679 )", "Background Provider misconceptions and biases about contraceptive methods are major barriers to family planning access for women in low- and middle-income countries , including Jordan . Evidence -Based Medicine ( EBM ) programs aim to reduce biases and misconceptions by providing doctors with the most up-to- date scientific evidence on contraceptive methods . Methods We evaluate the effects of an EBM program conducted in Jordan on private providers ’ knowledge , attitudes , and practice s. Family planning providers r and omly assigned to a treatment group were invited to attend a roundtable seminar on the injectable contraceptive Depot Medroxy Progesterone Acetate ( DMPA ) , and to receive two 15 min one-on-one educational visits that reinforce the messages from the seminar . Results There was low compliance with the EBM program . The study fails to detect an impact on providers ’ knowledge of DMPA ’s side effects or on reported clinical practice s. There is suggestive evidence of a positive impact on providers ’ attitudes toward and confidence in prescribing the contraceptive to their patients . There is also evidence of positive selection into program participation . Conclusions We conclude that EBM may not be effective as a st and -alone program targeting a family planning method with a high level of provider and consumer bias . Evidence of positive selection into program participation underscores the importance of r and omization to avoid overestimating the true effects of interventions .Trial registration AEA RCT Registry , AEA RCT R0000539 ,", "Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking . The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria ( mRDTs ) in registered drug shops in Ug and a , with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy ( ACT ) in patients seeking treatment for fever in drug shops . Methods A cluster-r and omized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district , central Ug and a. Ten clusters were r and omly allocated to the intervention ( diagnostic confirmation of malaria by mRDT followed by ACT ) and ten clusters to the control arm ( presumptive treatment of fevers with ACT ) . Treatment decisions by providers were vali date d by microscopy on a reference blood slide collected at the time of consultation . The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as : malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate , and patients with no malaria parasites not given ACT . Findings A total of 15,517 eligible patients ( 8672 intervention and 6845 control ) received treatment for fever between January-December 2011 . The proportion of febrile patients who received appropriate ACT treatment was 72·9 % versus 33·7 % in the control arm ; a difference of 36·1 % ( 95 % CI : 21·3 – 50·9 ) , p to purchase an mRDT ( 97·8 % ) , of whom 58·5 % tested mRDT-positive . Drug shop vendors adhered to the mRDT results , reducing over-treatment of malaria by 72·6 % ( 95 % CI : 46·7– 98·4 ) , p substantially improved appropriate treatment of malaria with ACT . Trial Registration Clinical Trials.gov NCT01194557", "In a cluster r and omized trial , Beth Kangwana and colleagues find that provision of subsidized packs of the malaria therapy artemether-lumefantrine to shops more than doubled the proportion of children with fever who received drugs promptly", "Background Malaria is a major public health problem in Ug and a and the current policy recommends introduction of rapid diagnostic tests for malaria ( RDTs ) to facilitate effective case management . However , provision of RDTs in drug shops potentially raises a new set of issues , such as adherence to RDTs results , management of severe illnesses , referral of patients , and relationship with caretakers . The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Ug and a and document lessons and policy implication s for future scale-up of malaria control in the private health sector . Methods A cluster-r and omized trial introducing RDTs into registered drug shops was implemented in central Ug and a from October 2010 to July 2012 . An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops , the lessons learned and policy implication s. Results Introducing RDTs into drug shops was feasible . To scale-up this intervention however , drug shop practice s need to be regulated since the registration process was not clear , supervision was inadequate and record keeping was poor . Although initially it was anticipated that introducing a new practice of record keeping would be cumbersome , but at evaluation this was not found to be a constraint . This presents an important lesson for introducing health management information system into drug shops . Involving stakeholders , especially the district health team , in the design was important for ownership and sustainability . The involvement of village health teams in community sensitization to the new malaria treatment and diagnosis policy was a success and this strategy is recommended for future interventions . Conclusion Introducing RDTs into drug shops was feasible and it increased appropriate treatment of malaria with artemisinin-based combination therapy . It is anticipated that the lessons presented will help better implementation of similar interventions in the private sector", "Objective To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present , with the aim of reducing current massive overdiagnosis and overtreatment of malaria . Design Cluster r and omized trial of 24 clusters of shops . Setting Dangme West , a poor rural district of Ghana . Participants Shops and their clients , both adults and children . Interventions Providing rapid diagnostic tests with realistic training . Main outcome measures The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial . Secondary outcomes were use of antibiotics and antipyretics , and safety . Results Of 4603 clients , 3424 ( 74.4 % ) tested negative by double-read research slides . The proportion of slide-negative clients who received any antimalarial was 590/1854 ( 32 % ) in the intervention arm and 1378/1570 ( 88 % ) in the control arm ( adjusted risk ratio 0.41 ( 95 % CI 0.29 to 0.58 ) , P agreement with rapid diagnostic test result . Of those who were slide-positive , 690/787 ( 87.8 % ) in the intervention arm and 347/392 ( 88.5 % ) in the control arm received an artemisinin combination therapy ( adjusted risk ratio 0.96 ( 0.84 to 1.09 ) ) . There was no evidence of antibiotics being substituted for antimalarials . Overall , 1954/2641 ( 74 % ) clients in the intervention arm and 539/1962 ( 27 % ) in the control arm received appropriate treatment ( adjusted risk ratio 2.39 ( 1.69 to 3.39 ) , P safety concerns were identified . Conclusions Most patients with fever in Africa present to the private sector . In this trial , providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria , did not reduce prescribing of antimalarials to true malaria cases , and appeared safe . Rapid diagnostic tests should be considered for the informal private drug retail sector . Registration Clinical trials.gov", "Background Sexually transmitted diseases ( STD ) are important co-factors in HIV transmission . We studied the impact of health worker training and STD syndrome packets ( containing recommended drugs , condoms , partner notification cards and information leaflets ) on the quality of STD case management in primary care clinics in rural South Africa . Methods A r and omized controlled trial of five matched pairs of clinics compared the intervention with routine syndromic management . Outcomes were measured by simulated patients using st and ardized scripts , and included the proportion given recommended drugs ; correctly case managed ( given recommended drugs plus condoms and partner cards ) ; adequately counselled ; reporting good staff attitude ; and consulted in privacy . Results At baseline , the quality of STD case management was similarly poor in both groups . Only 36 and 46 % of simulated patients visiting intervention and control clinics , respectively , were given recommended drugs . After the intervention , intervention clinics provided better case management than controls : 88 versus 50 % ( P correctly case managed ; 68 versus 46 % ( P = 0.06 ) were adequately counselled ; 84 versus 58 % experienced good staff attitude ( P = 0.07 ) ; and 92 versus 86 % ( P = 0.4 ) were consulted privately . A syndrome packet cost US$ 1.50 ; the incremental cost was US$ 6.80 . The total intervention cost equalled 0.3 % of annual district health expenditure . Interpretation A simple and affordable health service intervention achieved substantial improvements in STD case management . Although this is a critical component of STD control and can reduce HIV transmission , community-level interventions to influence health-seeking behaviour are also needed", "Small-scale interventions on training medicine retailers on malaria treatment improve over-the-counter medicine use , but there is little evidence on effectiveness when scaled up . This study evaluated the impact of Ministry of Health ( MoH ) training programs on the knowledge and practice s of medicine retailers in three districts in Kenya . A cluster r and omized trial was planned across 10 administrative divisions . Findings indicated that 30.7 % ( 95 % confidence interval [ CI ] : 23.3 , 39.0 ) and 5.2 % ( 95 % CI : 2.1 , 10.3 ) of program and control retailers , respectively , sold MoH amodiaquine with correct advice on use to surrogate clients ( OR = 8.8 ; 95 % CI : 2.9 , 26.9 ; P reported correct knowledge on dosing with amodiaquine ( OR = 29.8 ; 95 % CI : 8.2 , 108.8 ) . Large-scale retailer training programs within the national malaria control framework led to significant improvements in retailers ' practice s across three districts", "BACKGROUND Interventions to treat STDs have been reported to reduce HIV incidence . Interventions to improve treatment-seeking for STDs may impact on the duration and prevalence of STDs . Nigeria has high rates of STDs and an increasing incidence of HIV . OBJECTIVE To evaluate the impact of an intervention on STD treatment-seeking behavior and STD prevalence among Nigerian youth . METHODS A r and omized controlled trial in 12 schools in Edo State was conducted to evaluate an intervention to improve STD treatment-seeking and STD treatment provision . The intervention , based on formative research , consisted of community participation , peer education , public lectures , health clubs in the schools , and training of STD treatment providers , including those with no formal training . A question naire measured outcomes before and 10 months into the intervention . The effect of the intervention among four r and omly selected intervention schools compared to eight r and omly selected control schools was assessed using logistic regression with Huber 's formula to account for school clusters . RESULTS One thous and eight hundred and ninety-six and 1858 youths 14 - 20 years of age were enrolled in the pre- and post-intervention surveys . Youths in the intervention schools , compared to control schools , reported statistically significant improvements in knowledge of STDs , condom use , partner awareness that the youth had an STD , and STD treatment-seeking behavior . Treatment by private physicians increased ( OR=2.1 , 95 % CI=1.1 - 4.0 ) , and treatment by patent medicine dealers or pharmacists decreased ( OR=0.44 , 95 % CI=0.22 - 0.88 ) . The reported prevalence of STD symptoms in the past 6 months was significantly reduced in the intervention compared to control schools ( OR=0.68 , 95 % CI=0.48 - 0.95 ) . CONCLUSION Significant improvements in treatment-seeking for STD symptoms can be effected among Nigerian youths . The prevalence of reported STD symptoms can be decreased by improving treatment-seeking for and awareness of STDs", "Our goal was to evaluate and analyze physicians ' adherence to the national malaria policy in Antananarivo , 5 years after its revision . This prospect i ve descriptive study was conducted in public and private health centers in Antananarivo in 2010 , from May 1 to June 30 . Adhesion to the new policy included adoption of the rapid diagnostic test for malaria ( RDT ) and /or microscopy as diagnostic methods and prescription of artemisinin-based combination therapy ( ACT ) as first-line treatment for uncomplicated malaria . A question naire was used to collect data from 106 physicians . Their average age was 43.9 years ( range : 26 to 59 years ) . The male-female sex-ratio was 0.59 . Physicians trained in using RDTs were confident in this means of diagnosis ( p ACT by physicians was associated with their participation in malaria training ( p = 0.02 ) . Only 2/3 of the physicians adhered to the current policy . Adherence increased with trust ( p availability of RDT ( p training about the policy . Physician adhesion , training and confidence are essential to this policy and to changing physician behavior . Improvement of the health system is also needed", "OBJECTIVE Using simulated client and provider interview methods , this study assessed chemists and druggists ' post-training management quality of syndromic sexually transmitted infections focusing on the areas of privacy maintaining , encouraging , history taking , counseling , referral practice , partner notification , and drug prescribing and then compared the findings of two methods . DESIGN Forty-five pharmacies from a list of 75 in Pokhara , who collected sexually transmitted infections data during 1999 , were selected r and omly . First simulated client successfully presented either urethral or vaginal discharge syndrome at 37 pharmacies and recorded the events of whole encounter into an observation form within 20 minutes . Later 39 chemists and druggists were interviewed by a pre-tested semi-structured question naire . MAIN MEASURE Results were reported mainly by numbers and corresponding percentages . For comparative purpose , P values were also shown . RESULTS Overall , interview method revealed satisfactory knowledge of chemists and druggists for management of sexually transmitted infections except drug prescribing but their actual behaviors , revealed by simulated client method , indicated lower quality and differed significantly in the areas of encouraging , history taking , counseling , referral practice , and partner notification . Both methods indicated very poor qualities of drug prescribing . CONCLUSION Retained knowledge of chemists and druggists for syndromic management of sexually transmitted infections were not applied to simulated client in actual practice . They should not prescribe drugs for patients of sexually transmitted infections , except referring to the doctors/hospitals . Continuous monitoring and further motivations for them may improve syndromic management quality of sexually transmitted infections . Moreover , depending on the purpose of study , various methods should be applied simultaneously to reach a better conclusion", "OBJECTIVES To assess the effectiveness of a multi-component intervention on knowledge and reported practice amongst staff working in private pharmacies in Hanoi regarding four conditions : urethral discharge [ sexually transmitted diseases ( STD ) ] , acute respiratory infection ( ARI ) , and non-prescription requests for antibiotics and steroids . METHOD R and omized controlled trial with staff working in 22 matched pair intervention and control private pharmacies who were administered a semistructured question naire on the four conditions before and 4 months after the interventions . The interventions focused on the four conditions and were in sequence ( i ) regulations enforcement ; ( ii ) face-to-face education and ( iii ) peer influence . Outcome measures were knowledge and reported change in practice for correct management of tracer conditions . RESULTS The intervention/control-pairs ( 22 after drop-outs ) were analysed pre- and post-intervention using the Wilcoxon signed rank test . STD : More drug sellers stated they would ask about the health of the partner ( P = 0.03 ) and more said they would advise condom use ( P = 0.01 ) and partner notification ( P = 0.04 ) . ARI : More drug sellers stated they would ask questions regarding fever ( P = 0.01 ) , fewer would give antibiotics ( P = 0.02 ) and more would give traditional medicines ( P = 0.03 ) . Antibiotics request : Fewer said they would sell a few capsules of cefalexin without a prescription ( P = 0.02 ) . Steroid requests : No statistical difference was seen in the numbers who said they would sell steroids without a prescription as numbers declined in both intervention and control groups ( P = 0.12 ) . CONCLUSION The three interventions in series over 17 months were effective in changing the knowledge and reported practice of drug sellers in Hanoi", "Private pharmacies are the first line of health care in many communities , commonly selling antibiotics in small doses and prescription-only drugs such as steroids without medical supervision . The aim was to study the effectiveness of a multi-faceted intervention on the dispensing practice s of drug sellers in Hanoi and Bangkok . The study was a r and omized , controlled trial with 68 Hanoi and 78 Bangkok pharmacies , r and omly selected and assigned for intervention and control . Behaviour was assessed by five simulated client visits per pharmacy per dispensing practice , at baseline and a month or more after each intervention . Three three-month interventions were implemented sequentially with four months in between : enforcement of regulations with local inspectors visiting to emphasize the importance of prescription-only medicine legislation ; education , performed face-to-face in Hanoi and by a large group in Bangkok ; and peer review , voluntary in Bangkok and compulsory in Hanoi . The intervention result ed in significant improvements in Hanoi , reducing the dispensing of illegal steroids ( 29 % vs. 62 % ) and low dose antibiotics ( 69 % vs. 90 % ) , sustained by means of the peer review ( 17 % vs. 57 % steroids and 71 % vs. 95 % antibiotics ) , and in fewer dispensers asking no questions and giving no advice ( 11 % vs. 30 % steroids and 51 % vs. 81 % antibiotics ) . The only significant improvement in Bangkok was the reduction in illegally dispensing steroids ( 25 % vs. 44 % ) after the regulatory intervention . In Bangkok , fewer of those in the group who volunteered for the peer review asked no questions and gave no advice for low-dose antibiotics requests after the peer review ( 58 % vs. 81 % ) . A multi-component intervention can have a profound effect in changing dispensers ' behaviour , but the effect is dependant on the context and the method of implementation . Possible reasons for differences are discussed", "Private pharmacies are an important source of health care in developing countries . A number of studies have documented deficiencies in treatment , but little has been done to improve practice s. We conducted two controlled trials to determine the efficacy of face-to-face educational outreach in improving communication and product sales for cases of diarrhoea in children in 194 private pharmacies in two developing countries . A training guide was developed to enable a national diarrhoea control programme to identify problems and their causes in pharmacies , using quantitative and qualitative research methods . The guide also facilitates the design , implementation , and evaluation of an educational intervention , which includes brief one-on-one meetings between diarrhoea programme educators and pharmacists/owners , followed by one small group training session with all counter attendants working in the pharmacies . We evaluated the short-term impact of this intervention using a before- and -after comparison group design in Kenya , and a r and omized controlled design in Indonesia , with the pharmacy as unit of analysis in both countries ( n = 107 pharmacies in Kenya ; n = 87 in Indonesia ) . Using trained surrogate patients posing as mothers of a child under five with diarrhoea , we measured sales of oral rehydration salts ( ORS ) ; sales of antidiarrhoeal agents ; and history-taking and advice to continue fluids and food . We also measured knowledge about dehydration and drugs to treat diarrhoea among Kenyan pharmacy employees after training . Major discrepancies were found at baseline between reported and observed behaviour . For example , 66 % of pharmacy attendants in Kenya , and 53 % in Indonesia , reported selling ORS for the previous case of child diarrhoea , but in only 33 % and 5 % of surrogate patient visits was ORS actually sold for such cases . After training , there was a significant increase in knowledge about diarrhoea and its treatment among counter attendants in Kenya , where these changes were measured . Sales of ORS in intervention pharmacies increased by an average of 30 % in Kenya ( almost a two-fold increase ) and 21 % in Indonesia compared to controls ( p antidiarrhoeal sales declined by an average of 15 % in Kenya and 20 % in Indonesia compared to controls ( p communication in both countries , and in Kenya we observed significant increases in discussion of dehydration during pharmacy visits ( p positive effects and cost-effectiveness of such programmes need to be tested over a longer period for other health problems and in other countries", "BACKGROUND In most Asian countries , 50 - 90 % of pharmaceutical sales are made in private drug outlets , by personnel with some training in drugs but not for the treatment of common health problems . The objective of the study was to determine effects of focused training for private drug sellers to improve practice s in treating acute respiratory infections and diarrhoea in children , and anaemia in pregnancy in Nepal . METHODS R and omized controlled , four way nested design study incorporating four interventions for drug retailers in both hill and terai districts . One group received mailed printed educational material s followed by mailed feedback ; a second received small group training followed by feedback ; a third received small group training only ; and a fourth , the control group , received no intervention . Surrogate customer method was used to assess practice s. Outcomes were measured using multivariate linear regression . RESULTS A significant increase in the asking of key history questions , recommendation ( prescribing by drug retailers ) of cotrimoxazole , and advice-giving for pneumonia ; a significant increase in ORS recommendation , and advice giving for diarrhoea including the avoidance of antidiarrhoeals ; and a significant increase in asking key history questions and recommending appropriate products in pregnancy cases . CONCLUSIONS Training intervention as well as training followed by practice feedback was effective in improving the management of common illnesses and pregnancy by private drug sellers", "In Tlaxcala State , Mexico , we determined that 80 % of children who died from diarrhoea or acute respiratory infections ( ARI ) received medical care before death ; in more than 70 % of the cases this care was provided by a private physician . Several strategies have been developed to improve physicians ' primary health care practice s but private practitioners have only rarely been included . The objective of the present study was to evaluate the impact of in-service training on the case management of diarrhoea and ARI among under-5-year-olds provided by private and public primary physicians . The training consisted of a five-day course of in-service practice during which physicians diagnosed and treated sick children attending a centre and conducted clinical discussion s of cases under guidance . Each training course was limited to six physicians . Clinical performance was evaluated by observation before and after the courses . The evaluation of diarrhoea case management covered assessment of dehydration , hydration therapy , prescription of antimicrobial and other drugs , advice on diet , and counselling for mothers ; that of ARI case management covered diagnosis , decisions on antimicrobial therapy , use of symptomatic drugs , and counselling for mothers . In general the performance of public physicians both before and after the intervention was better than that of private doctors . Most aspects of the case management of children with diarrhoea improved among both groups of physicians after the course ; the proportion of private physicians who had five or six correct elements out of six increased from 14 % to 37 % : for public physicians the corresponding increase was from 53 % to 73 % . In ARI case management , decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups ; the proportion of private physicians with at least three correct elements out of four increased from 13 % to 42 % , while among public doctors the corresponding increase was from 43 % to 78 % . H and s-on training courses thus seemed to be effective in improving the practice of physicians in both the private and public sectors", "The objective of this study was to assess the effects of a multicomponent intervention on private pharmacy practice . From 641 private pharmacies in Hanoi , 68 pharmacies were r and omly selected and matched into 34 pairs . Each pair consisted of a control and an intervention pharmacy . Three interventions were applied sequentially : Regulatory enforcement , Education , and Peer influence . Four tracer conditions were selected : uncomplicated acute respiratory infection ( ARI ) , sexually transmitted disease ( STD ) , requesting the prescription-only drugs prednisolone , and a short course of cefalexin . Practice was assessed through the Simulated Client Method ( SCM ) . The intervention pharmacies improved significantly compared to the control pharmacies ( P ARI , antibiotic dispensing decreased ( P questions regarding breathing increased ( P STD , advice to go to the doctor and dispensing the correct syndromic treatment increased ( P Dispensing of prednisolone and cefalexin decreased ( P prescription requests increased ( P pharmacy practice with a multicomponent intervention" ]	411836d2-06ff-11f0-808a-c43d1ab1c353
BACKGROUND An up-to- date overview of the effectiveness and safety of dynamic exercise therapy ( exercise therapy with a sufficient intensity , duration , and frequency to establish improvement in aerobic capacity and /or muscle strength ) is lacking . OBJECTIVES To assess the effectiveness and safety of short-term ( three months ) dynamic exercise therapy programs ( aerobic capacity and /or muscle strength training ) , either l and or water-based , for people with RA . To do this we up date d a previous Cochrane review ( van den Ende 1998 ) and made categories for the different forms of dynamic exercise programs . SEARCH STRATEGY A literature search ( to December 2008 ) within various data bases was performed in order to identify r and omised controlled trials ( RCTs ) . SELECTION CRITERIA RCTs that included an exercise program fulfilling the following criteria were selected : a ) frequency at least twice weekly for > 20 minutes ; b ) duration > 6 weeks ; c ) aerobic exercise intensity > 55 % of the maximum heart rate and /or muscle strengthening exercises starting at 30 % to 50 % of one repetition maximum ; and d ) performed under supervision . Moreover , the RCT included one or more of the following outcome measures : functional ability , aerobic capacity , muscle strength , pain , disease activity or radiological damage . DATA COLLECTION AND ANALYSIS Two review authors independently selected eligible studies , rated the method ological quality , and extracted data . A qualitative analysis ( best- evidence synthesis ) was performed and , where appropriate , a quantitative data analysis ( pooled effect sizes ) . MAIN RESULTS In total , eight studies were included in this up date d review ( two additional studies ) . Four of the eight studies fulfilled at least 8/10 method ological criteria . In this up date d review four different dynamic exercise programs were found : ( 1 ) short-term , l and -based aerobic capacity training , which results show moderate evidence for a positive effect on aerobic capacity ( pooled effect size 0.99 ( 95 % CI 0.29 to 1.68 ) . ( 2 ) short-term , l and -based aerobic capacity and muscle strength training , which results show moderate evidence for a positive effect on aerobic capacity and muscle strength ( pooled effect size 0.47 ( 95 % CI 0.01 to 0.93 ) . ( 3 ) short-term , water-based aerobic capacity training , which results show limited evidence for a positive effect on functional ability and aerobic capacity . ( 4 ) long-term , l and -based aerobic capacity and muscle strength training , which results show moderate evidence for a positive effect on aerobic capacity and muscle strength . With respect to safety , no deleterious effects were found in any of the included studies . AUTHORS ' CONCLUSIONS Based on the evidence , aerobic capacity training combined with muscle strength training is recommended as routine practice in patients with RA	[ "The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity . Maximal O2 uptake increased significantly , whereas heart rate at stage 2 and rate of perceived exertion decreased significantly , in the training group compared with the controls . Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training . Training did not induce changes in blood mononuclear cell sub population s , proliferative response , or natural killer cell activity . Furthermore the plasma concentrations of interleukin-1 alpha , interleukin-1 beta , and interleukin-6 did not change in response to training . It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis", "OBJECTIVE To evaluate the short term efficacy of a community based physical therapy ( PT ) program for people with rheumatoid arthritis ( RA ) through a single blind r and omized controlled trial . METHODS Adults with active RA were referred by their physician for community based PT . Participants were r and omized to either an immediate intervention group [ experimental group ( EG ) ] or a wait list control group ( CG ) . The intervention was a st and ardized program of education and exercise consisting of at least 4 visits or 3 h of PT over 6 weeks . Baseline , 6 , and 12 week assessment s were by a blinded independent assessor . The primary outcome instrument was the Stanford Arthritis Self-Efficacy Scale ( SES ) and secondary outcome measures included the ACREU Rheumatoid Arthritis Knowledge Question naire ( KQ ) and visual analog scale for pain ( VAS ) . Duration of morning stiffness , grip strength , and tender joint count were also collected at each assessment . Outcome analysis was conducted using analysis of variance . RESULTS Of 150 eligible and r and omized participants , 127 completed the study according to protocol . Baseline analysis showed no differences between the EG and CG for demographics , disease status , or other characteristics . At the 6 week assessment , primary outcome analysis for those who completed the protocol identified a mean change ( improvement ) of 13.5 % in the EG and 5.8 % in the CG , representing a 7.7 % difference in change scores between the 2 groups [ F(1,121 ) = 6.03 ; p = 0.015 ] . A statistically significant difference in change scores was also identified for the KQ [ F(1,120 ) = 6.67 ; p = 0.011 ] , but not for the VAS . Disease status measures did not change , except for duration of morning stiffness , which improved by 68.8 min in the EG and 8.3 min in the CG ( F(1,121 ) = 4.50 ; p = 0.036 ] . CONCLUSION Four hours of a community based PT intervention delivered over 6 weeks significantly improved self-efficacy , disease management knowledge and morning stiffness in people with RA", "OBJECTIVE To estimate the cost utility and cost effectiveness of long-term , high-intensity exercise classes compared with usual care in rheumatoid arthritis ( RA ) patients . METHODS RA patients ( n = 300 ) were r and omly assigned to either exercise classes or UC ; followup lasted for 2 years . Outcome measures were quality -adjusted life years ( QALYs ) according to the EuroQol ( EQ-5D ) , Short Form 6D ( SF-6D ) , and a transformed visual analog scale ( VAS ) rating personal health ; functional ability according to the Health Assessment Question naire ( HAQ ) and McMaster Toronto Arthritis Patient Preference Interview ( MACTAR ) ; and societal costs . RESULTS QALYs in both r and omization groups were similar according to the EQ-5D and SF-6D , but were in favor of usual care according to the VAS ( annual difference 0.037 QALY ; 95 % confidence interval [ 95 % CI ] 0.002 , 0.069 ) . Functional ability was similar according to the HAQ , but in favor of the exercise classes according to the MACTAR ( annual difference 2.9 QALY ; 95 % CI 0.9 , 4.9 ) . Annual medical costs of the exercise program were estimated at 780 per participating patient ( 1 approximately $ 1.05 ) . The increase per patient in total medical costs of physical therapy was estimated at 430 ( 95 % CI 318 , 577 ) , and the increase in total societal costs at 602 ( 95 % CI -490 , 1,664 ) . For societal willingness-to-pay equal to 50,000 per QALY , usual care had better cost utility than exercise classes , and significantly so according to the VAS . CONCLUSION From a societal perspective and without taking possible preventive health effects into account , long-term , high-intensity exercise classes provide insufficient improvement in the valuation of health to justify the additional costs", "The aims of this study were to describe rheumatoid arthritis patients ’ compliance with continued exercise after participation in a 2-year supervised high-intensity exercise program and to investigate if the initially achieved effectiveness and safety were sustained . Data were gathered by follow-up of the participants who completed the 2-year high-intensity intervention in a r and omized controlled trial ( Rheumatoid Arthritis Patient In Training study ) . Eighteen months thereafter , measurements of compliance , aerobic capacity , muscle strength , functional ability , disease activity , and radiological damage of the large joints were performed . Seventy-one patients were available for follow-up at 18 months , of whom 60 ( 84 % ) were still exercising ( exercise group : EG ) , with average similar intensity but at a lower frequency as the initial intervention . Eleven patients ( 16 % ) reported low intensity or no exercises ( no-exercise group : no-EG ) . Patients in the EG had better aerobic fitness and functional ability , lower disease activity , and higher attendance rate after the initial 2-year intervention . At follow-up , both groups showed a deterioration of aerobic fitness and only patients in the EG were able to behold their muscle strength gains . Functional ability , gained during the previous participation in high-intensity exercises , remained stable in both groups . Importantly , no detrimental effects on disease activity or radiological damage of the large joints were found in either group . In conclusion , the majority of the patients who participated in the 24-month high-intensity exercise program continued exercising in the ensuing 18 months . In contrast to those who did not continue exercising , they were able to preserve their gains in muscle strength without increased disease activity or progression of radiological damage", "OBJECTIVES The aim of this study was to evaluate the effects of moderately intensive pool exercise therapy on patients with rheumatoid arthritis ( RA ) . METHODS Forty-six patients with chronic RA were r and omly assigned to a treatment group and a control group . The treatment group ( n = 20 ) exercised in a temperate pool twice a week for 12 weeks . The control group ( n = 23 ) continued with their previous activities . Aerobic capacity , measured by means of a submaximum bicycle test , and the physical component of the SF-36 were chosen as the primary outcome measures . Two tests of muscle endurance were chosen as the secondary outcome measure . Additional functional tests and instruments were included . RESULTS No significant differences between the groups were found for the primary outcome measures . Significant improvements in the following aspects of muscular function ( P isometric shoulder endurance , grip force , dynamic endurance of lower extremities ( chair test ) and muscle function of lower extremities . Significant improvements were also found for vitality ( SF-36 ) compared with the control group . The improvements in the training group were maintained for 3 months . CONCLUSIONS Pool exercise therapy of moderate intensity significantly improved muscle endurance in the upper and lower extremities in patients with RA , while no impact on aerobic capacity was found . However , the study population was small and there is a need for further studies with larger population", "The effects of detraining subsequent to strength training on neuromuscular function were examined in 39 recent-onset rheumatoid arthritis ( RA ) patients . Eighteen age- and sex-matched healthy people ( H ) served as controls . Patients were r and omly allocated either to the experimental group ( PE ) , who carried out progressive strength training for 6 months , or to the control group ( PC ) , who maintained only their habitual physical activities . After 6 months , PE returned to their earlier physical activities and strength training was terminated . At baseline , the maximal strength of the trunk extensors ( not significant ) , grip strength and maximal dynamic strength and the shape of the force-time curve of the knee extensors were lower in PE and PC ( P maximal strength of all muscle groups without changes in the shape of the force-time curve . The increases in muscle strength in PE obtained by strength training were lost to a great degree during the detraining period for the isometric trunk extension ( P knee extension strength ( P grip strength . In PC , trunk extension and flexion strength decreased significantly throughout the study period . At the post-test , all the strength values in both patient groups were much lower than in H. RA is a chronic disease which seems to need continuous physical exercise with sufficient intensity to minimize/prevent the loss of muscle strength and functional capacity", "OBJECTIVE To evaluate the effects of a 12 month , weight bearing , aerobic exercise program on disease activity , physical function , and bone mineral density ( BMD ) in women with rheumatoid arthritis ( RA ) taking low dose prednisone . METHODS A group of women with RA ( n = 23 ) not receiving steroid therapy and in American College of Rheumatology functional class I or II was compared to 30 steroid treated patients with similar demographics . The latter group was r and omized to usual care ( n = 16 ) or an aerobic , weight bearing exercise program ( n = 14 ) 3 times a week for 12 months . All subjects were recruited from an outpatient rheumatology clinic or physical therapy department and met the study inclusion criteria . Outcome measures included disease activity ( erythrocyte sedimentation rate , active joint count ) , physical function ( Health Assessment Question naire disability index , activity level ) and BMD of the spine and femoral neck ( by dual energy projection radiology ) . RESULTS Subjects in the exercise group had a small but nonsignificant decrease in disease activity and statistically significant improvements in function ( p = 0.05 ) and activity levels ( p = 0.05 ) . BMD remained unchanged in the exercise group , decreased significantly ( p = 0.004 ) in the nonsteroid comparison group ( hip ) , and changed nonsignificantly in the control group . However , between-group changes in spinal BMD of the steroid treated groups was not significant ( p = 0.09 ) . CONCLUSION Women with RA taking low dose steroid therapy can safely participate in a dynamic , weight bearing exercise program with positive effects on their physical function , activity and fitness levels , and BMD with no exacerbation of disease activity ", "OBJECTIVE To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the h and s and feet in patients with rheumatoid arthritis ( RA ) . METHODS Data of the 281 completers of a 2 year r and omised controlled trial comparing the effects of usual care physical therapy ( UC ) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage ( Larsen score ) of the h and s and feet . Potential determinants of outcome were defined : disease activity , use of drugs , change in physical capacity and in bone mineral density , and attendance rate at exercise sessions . RESULTS After 2 years , the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC . The mean ( SD ) increase in damage was 3.5 ( 7.9 ) in the exercise group and 5.7 ( 10.2 ) in the UC group , p = 0.045 . Separate analysis of the damage to the h and s and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the h and s. The rate of damage was independently associated with less disease activity , less frequent use of glucocorticoids , and with an improvement in aerobic fitness . CONCLUSION The progression of radiological joint damage of the h and s and feet in patients with RA is not increased by long term high intensity weightbearing exercises . These exercises may have a protective effect on the joints of the feet", "OBJECTIVE To investigate the effects of a 21-week concurrent strength and endurance training protocol on physical fitness profile in women with early or longst and ing rheumatoid arthritis ( RA ) compared with healthy subjects . METHODS Twenty-three female patients with RA volunteered for the study . Twelve had early RA and eleven had longst and ing RA . Twelve healthy women served as controls . Maximal strength of different muscle groups was measured by dynamometers , walking speed with light cells , and vertical squat jump on the force platform to mirror explosive force . Maximal oxygen uptake was measured by gas analyzer . Six training sessions ( 3 strength training and 3 endurance training ) were carried out in a 2-week period for 21 weeks . RESULTS The training led to large gains in maximal strength both in women with RA and in healthy women ( P strength gains were accompanied by increases in walking speed ( P vertical squat jump ( P maximal aerobic capacity in all groups ( P Both early and longst and ing RA patients with stable disease can safely improve all characteristics of their physical fitness profile using a progressive concurrent strength and endurance training protocol", "OBJECTIVES To compare quadriceps sensorimotor function , lower limb functional performance and disability in patients with rheumatoid arthritis ( RA ) and healthy subjects , and to investigate the efficacy and safety of a brief rehabilitation regime . METHODS Quadriceps strength , voluntary activation , proprioceptive acuity and the aggregate time [ aggregate functional performance time ( AFPT ) ] taken to perform four common activities [ aggregate functional performance time ( AFPT ) ] were compared between 103 RA patients who had lower limb involvement and 25 healthy subjects . In addition , disability ( Health Assessment Question naire ) , clinical disease activity and the plasma concentration of proinflammatory cytokines were measured in the RA patients . In a follow-on r and omized controlled trial of rehabilitation , these variables were used as baseline data for 93 of the RA patients , who were r and omized to a rehabilitation or a control group . Changes in the variables were analysed within and between groups . RESULTS Compared with healthy subjects , RA patients had weaker quadriceps [ mean difference 157 N ; 95 % confidence interval ( CI ) 125 - 189 ] , poorer activation ( 8 % , 95 % CI 4.5 - 15 ) and proprioceptive acuity ( 0.8 degrees , 95 % CI 0.4 - 1.3 ) and took longer to perform the AFPT ( 34 s , CI 23.5 - 44.8 ) . Rehabilitation increased quadriceps strength ( mean increase 61 N , 95 % CI 28 - 95 ) and voluntary activation ( 8 % , 95 % CI 3 - 12.4 ) and decreased the AFPT ( 12.3 s , 95 % CI -2 to 27.7 ) and subjective disability ( 0.21 HAQ points , 95 % CI 0 - 0.35 ) without exacerbating disease activity . All the improvements were maintained at the 6-month follow-up . There was no change during the control period . CONCLUSIONS Patients with RA that affected their lower limb had quadriceps sensorimotor deficits that were associated with lower limb disability . A clinical ly applicable rehabilitation regime increased quadriceps sensorimotor function and decreased lower limb disability without exacerbating pain or disease activity . For patients with well-controlled RA that causes lower limb involvement , the regime is effective and safe", "OBJECTIVE To investigate physical fitness and work capacity in women with rheumatoid arthritis ( RA ) . METHODS The 42 subjects were a subset of a prospect i ve trial of conditioning exercise in rheumatic disease . Assignment to an exercise or nonexercise group was determined by proximity to the intervention , a 3-month supervised group exercise program . Physical fitness and work capacity were assessed at baseline , 3 months , and 12 months . RESULTS At baseline , subjects were deconditioned and limited in h and function , lifting ability , and lower extremity mobility . Only the exercise group improved their aerobic capacity and exercise tolerance . There were no significant changes in measured work capacity in either group . Moderate to strong correlations were found between aerobic capacity , mobility , h and function , and work capacity . Grip strength was a strong and consistent correlate of work capacity . CONCLUSION Our findings suggest that physical capacity , particularly h and function , may be important in the complex phenomenon of work disability in RA", "OBJECTIVES The McMaster Toronto Arthritis patient preference question naire ( MACTAR ) is a functional index that measures change in impaired activities selected by each patient in a baseline interview , and change in rheumatoid arthritis ( RA ) disease activity . In addition , it contains questions on the state of physical , social and emotional function and overall health , and their relation to RA . We evaluated MACTAR 's feasibility and validity ( content validity , construct validity , and responsiveness ) . METHODS A r and omized trial of combined treatment in 155 patients with early RA ; patients ' mean age at baseline was 50 years and median disease duration since diagnosis was 4 months . RESULTS Feasibility : MACTAR requires trained interviewers . In the trial , interviews took about 15 min . In longer term followup , activities selected at baseline may become less relevant as the pattern of disability changes . Followup from 153 patients ( 99 % ) was available . At least 5 impaired activities were identified and ranked by 147 patients ( 95 % ) ; interviewers could follow 99 % of these . The scoring system proved complex and required amendments . Content validity : Although its main focus is physical function , the MACTAR also contains generic questions ; 75 % of the patients named at least one impaired activity from the category \" mobility . \" Only 48 % were covered by Health Assessment Question naire ( HAQ ) items . Construct validity : MACTAR scores correlate highly with other functional indices and with measures of disease activity . Responsiveness : At 16 weeks the st and ardized response mean for the total MACTAR score in the combined-treatment group was excellent , at 2.2 . Items that directly address change were even more responsive . CONCLUSION The MACTAR interview is a valid and highly responsive instrument to assess change in functional ability of patients with early RA with active disease . It provides insight into problems -- mainly of physical function -- that really matter to patients . For st and ard clinical trials and clinical care , feasibility of the MACTAR is limited and the simpler HAQ remains the instrument of choice", "OBJECTIVE To investigate at 5 years whether an initial 2 year home based strength training period imposes sustained effects on muscle strength , bone mineral density ( BMD ) , structural joint damage , and on disease activity in patients with early rheumatoid arthritis ( RA ) . METHODS Seventy patients were r and omised either to perform home based strength training with loads of 50 - 70 % of repetition maximum ( EG ) or range of motion exercises ( CG ) . Both groups were encouraged to take part in aerobic activities 2 - 3 times a week . Maximal muscle strength of different muscle groups was measured by dynamometers , and BMD at the femoral neck and lumbar spine by dual x ray densitometry . Disease activity was assessed by the 28 joint disease activity score , and joint damage by x ray findings . RESULTS 62 patients completed 2 years ' training and 59 patients attended check up at 5 years . Mean ( SD ) maximum muscle strength indices increased from baseline to 2 years-in EG from 212 ( 78 ) kg by a mean ( 95 % CI ) of 68 ( 55 to 80 ) and in CG from 195 ( 72 ) kg by 35 ( 13 to 60 ) kg- and remained at that level for the next 3 years . Development of BMD in EG tended to be more favourable than that in CG . Muscle strength training was not detrimental to joint structures or disease activity . CONCLUSION The patients ' exercise induced muscle strength gains during a 2 year training period were maintained throughout a subsequent self monitored training period of 3 years . Despite substantial training effects in muscle strength , BMD values remained relatively constant . Radiographic damage remained low even at 5 years", "The objective was to study the long-term effect ( 2 years ) of different training programs in patients with rheumatoid arthritis . The method was a r and omized trial with 75 patients participating . The measured variables included morning stiffness , a pain score , number of swollen joints , a health assessment score , a functional score , ESR , Hb , the cost of medicine , and progression using X-rays of h and s and feet . The results showed no effect of training on the disease activity or on the progression of the disease . The conclusion is that although most patients are in favour of training , the present study does not support that training lessons per se affect the disease activity or the progression of the disease", "OBJECTIVE To evaluate the effectiveness of three different physiotherapeutic approaches in the management of the rheumatoid h and . METHODS In a r and omized controlled trial , participants with rheumatoid arthritis ( RA ) recruited from a rheumatology department in Mid-Staffordshire , UK ( February 1999 to January 2001 ) were r and omized to three groups . All received joint protection ( JP ) information delivered by a therapist at baseline . Group 1 participants received a set of additional h and -strengthening and mobilizing home exercises , group 2 a different set of additional h and -stretching exercises and group 3 the JP information alone . The primary outcome was the Arthritis Impact Measurement Scales II ( AIMS II ) ( upper limb ; h and and finger function subscales ) . Outcomes were assessed at baseline and 1 , 3 and 6 months . Analysis was by intention to treat . RESULTS Sixty-seven participants ( mean age 59.6 yr ) were recruited : group 1 n = 21 , group 2 n = 24 and group 3 n = 22 . A 78 % follow-up was achieved at 6 months . There was a mean fall ( SD ) in AIMS II upper limb function 0 - 6 month change scores in group 1 of 1.00 ( 1.07 ) . In groups 2 and 3 there was a mean increase in AIMS II scores of 0.18 ( 1.54 ) and 0.30 ( 1.22 ) , respectively . The differences in AIMS change scores between group 1 and groups 2 and 3 were statistically significant ( P = 0.007 ) and remained so after adjustment for multiple testing ( P = 0.012 ) . CONCLUSION Statistically significant improvements in arm function have been demonstrated following a programme of home-strengthening h and exercises in RA patients compared with simple stretches or advice alone", "OBJECTIVE To evaluate the impact of a 2-year program of strength training on muscle strength , bone mineral density ( BMD ) , physical function , joint damage , and disease activity in patients with recent-onset ( METHODS In this prospect i ve trial , 70 RA patients were r and omly assigned to perform either strength training ( all major muscle groups of the lower and upper extremities and trunk , with loads of 50 - 70 % of repetition maximum ) or range of motion exercises ( without resistance ) twice a week ; all were encouraged to engage in recreational activities 2 - 3 times a week . All patients completed training diaries ( evaluated bi-monthly ) and were examined at 6-month intervals . All were treated with medications to achieve disease remission . Maximum strength of the knee extensors , trunk flexors and extensors , and grip strength was measured with dynamometers . BMD was measured at the femoral neck and lumbar spine by dual x-ray densitometry . Disease activity was determined by the Disease Activity Score , the extent of joint damage by the Larsen score , and functional capacity by the Health Assessment Question naire ( HAQ ) ; walking speed was also measured . RESULTS Sixty-two patients ( 31 per group ) completed the study . Strength training compliance averaged 1.4 - 1.5 times/week . The maximum strength of all muscle groups examined increased significantly ( 19 - 59 % ) in the strength-training group , with statistically significant improvements in clinical disease activity parameters , HAQ scores , and walking speed . While muscle strength , disease activity parameters , and physical function also improved significantly in the control group , the changes were not as great as those in the strength-training group . BMD in the femoral neck and spine increased by a mean + /- SD of 0.51 + /- 1.64 % and by 1.17 + /- 5.34 % , respectively , in the strength-training group , but decreased by 0.70 + /- 2.25 % and 0.91 + /- 4.07 % in the controls . Femoral neck BMD in the 17 patients with high initial disease activity ( and subsequent use of oral glucocorticoids ) remained constantly at a statistically significantly lower level than that in the other 45 patients . CONCLUSION Regular dynamic strength training combined with endurance-type physical activities improves muscle strength and physical function , but not BMD , in patients with early RA , without detrimental effects on disease activity", "Twenty-six patients with rheumatoid arthritis ( RA ) participated either in a 21 day , community sponsored , in-patient multidisciplinary rehabilitation program ( N = 20 ) or ; received traditional , out-patient physiotherapy design ed by the patient 's rheumatologist ( N = 6 ) . Clinical assessment s were made ( prior to , immediately after , and 6 months after rehabilitation ) to evaluate the response to these two quite different rehabilitative measures that included : functional classification , joint score index , subjective VAS of pain , HAQ , pain disability index , Comprehensible psychopathological rating scale , hemoglobin , and CRP measurements . Economic assessment s included salary , direct and community sponsored costs , for rehabilitation and costs for sick days and production losses . No clear-cut differences between the two rehabilitation modes were detected . Both modes showed improvement in different assessment parameters ; patients with higher education and , therefore , with a less joint-disturbing work profile appeared to profit more from an extensive in-patient rehabilitation program . Patients with less education and a more manually-oriented working profile , did worse and had a higher tendency to seek medical pensioning , in spite of rehabilitative measures . As the total costs for out-patient rehabilitation only add up to 15.8 % of the total costs for in-patient rehabilitation , this study setting cautiously suggests that out-patient rehabilitation might be an acceptable alternative to individualized patient groups that might not compromise clinical and vocational outcome . Larger patient groups are needed , however , to confirm these findings", "The aim of the study was to evaluate the effects of a dynamic training program versus a muscle relaxation training program as home exercise in patients with inflammatory rheumatic diseases . Fifty-four patients ( mean age 54 years , mean symptom duration 14 years ) were r and omized to one of the two programs . After personal instructions every patient exercised at home for half an hour , 5 days a week during 3 months . Before and after the interventions , all patients were assessed for health-related quality of life , joint tenderness and physical capacities . The dynamic training group had improved in perceived exertion at the walking test ( p training group had improved their total Nottingham Health Profile ( p subscale for lack of energy ( p Ritchie 's articular index ( p muscle function of the lower extremities ( p arm endurance ( p changes in muscle function of the lower extremities during the intervention period , there was a significant difference ( p progressive muscle relaxation training might improve health related quality of life , reduce joint tenderness and be superior to dynamic muscle training in improving the muscle function of the lower extremities in patients with inflammatory rheumatic diseases . The clinical effects were small and the results have to be interpreted with caution", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "Thirty-nine consecutive patients with recent-onset rheumatoid or psoriatic arthritis were r and omly allotted for six months period either to the experimental progressive dynamic strength training group ( EG , 10 women and 11 men ; 41 + /- 10 yrs ) , or to the control group ( CG , 10 women and 8 men ; 45 + /- 11 yrs ) who just maintained their habitual physical activities . All patients received antirheumatic medication throughout the experimental period . During the study period significant improvements took place in the EG in maximal muscle strength of all examined muscle groups ( 31.5 % for the knee extensors , p erytrocyte sedimentation rate ( p Ritchie 's articular index ( RI ) ( p HAQ ( p RI was statistically significant ( p Erosive changes in joints increased only slightly and less in the EG than in the CG . The present results suggest that dynamic strength training in early arthritis increases the neuromuscular performance without detrimental effects on disease activity or joint damage", "The effectiveness of an exercise prescription and unsupervised home exercise programme was tested on 37 subjects with rheumatoid arthritis and 34 with systemic lupus erythematosus . Subjects were r and omly assigned to control or stationary bicycling at home , using loaned bicycles . Exercise subjects ( with bicycles ) did better than controls , but not significantly , on all outcome d measures ( exercise tolerance test , fatigue , depression and helplessness ) at 3 months . Bicycles were recl aim ed at 3 months and all subjects in both groups given instructions for home exercise . Exercise in the second 3 months was predicted primarily by baseline exercise habits and fatigue . It is concluded that although safe , unsupervised home exercise programmes may benefit few patients . Future research should address methods of stimulating and maintaining unsupervised exercise programmes in patients with systemic rheumatic disease", "OBJECTIVE The aim of this study was to evaluate the therapeutic effects of hydrotherapy which combines elements of warm water immersion and exercise . It was predicted that hydrotherapy would result in a greater therapeutic benefit than either of these components separately . METHODS One hundred thirty-nine patients with chronic rheumatoid arthritis were r and omly assigned to hydrotherapy , seated immersion , l and exercise , or progressive relaxation . Patients attended 30-minute sessions twice weekly for 4 weeks . Physical and psychological measures were completed before and after intervention , and at a 3-month followup . RESULTS All patients improved physically and emotionally , as assessed by the Arthritis Impact Measurement Scales 2 question naire . Belief that pain was controlled by chance happenings decreased , signifying improvement . In addition , hydrotherapy patients showed significantly greater improvement in joint tenderness and in knee range of movement ( women only ) . At followup , hydrotherapy patients maintained the improvement in emotional and psychological state . CONCLUSIONS Although all patients experienced some benefit , hydrotherapy produced the greatest improvements . This study , therefore , provides some justification for the continued use of hydrotherapy", "The effects of 12 weeks of low-impact aerobic exercise on fatigue , aerobic fitness , and disease activity were examined in a quasi-experimental time series study of 25 adults with rheumatoid arthritis ( RA ) . Measures were obtained preintervention , midtreatment ( after 6 weeks of exercise ) , end of treatment ( after 12 weeks of exercise ) , and at a 15-week follow-up . ANOVAS for repeated measures showed that those subjects who participated more frequently reported decreased fatigue , while those who participated less frequently reported an increase in fatigue . All subjects , on average , showed increased aerobic fitness and increased right and left h and grip strength , decreased pain , and decreased walk time . There were no significant increases in joint count or sedimentation rate . Significant improvements in measures at the 15-week follow-up also were found . Findings indicate that persons with RA who participate in appropriate exercises may lessen fatigue levels and experience other positive effects without worsening their arthritis", "OBJECTIVE To assess the effects of 12 months ' dynamic strength training on muscle strength and bone mineral density ( BMD ) at the lumbar spine and femoral neck in patients with early rheumatoid arthritis ( RA ) . METHODS Thirty-two subjects in the training group ( EG ) and 33 in the control group ( CG ) completed the study . EG carried out strength training 2 times a week with moderate loads of 50 - 70 % of repetition maximum . They were also encouraged to do recreational physical activities . CG performed recreational physical activities and range of motion exercises . Maximal strength of the knee extensors , trunk extensors and flexors , and grip strength were recorded with dynamometers . BMD was measured using dual x-ray absorptiometry . Modified Disease Activity Score , erythrocyte sedimentation rate , and pain were used for the estimation of disease activity , and Stanford Health Assessment Question naire to measure functional disability . RESULTS The 12 month resistance training in EG led to statistically significant mean increases of 22 - 35 % in all muscle groups examined . CG patients were also able to increase their strength to some degree ( 3 - 24 % ) , but at the end of the study strengths in CG were significantly lower than in EG . By the end of the study lumbar spine BMD had changed by + 0.19 % ( 4.24 ) in EG and by -1.14 % ( 4.36 ) in CG . The corresponding changes of femoral BMD were + 1.10 % ( 3.71 ) and -0.03 % ( 3.58 ) . The changes in BMD were minor and statistically not significant in both groups . However , femoral BMD was found to be decreased among those patients treated periodically with oral glucocorticoids ( n = 15 , 3 subjects from EG and 12 from CG ) compared with changes in BMD among those not treated with systemic glucocorticoids ( n = 50 ) . CONCLUSION Minimally supervised strength training result ed in significant improvements in muscle strength without detrimental effects on disease activity . The detected annual changes in central BMD were minor and statistically insignificant in both groups . Special attention should be focused on those patients with RA with high disease activity and concomitant glucocorticoid treatment", "OBJECTIVE To determine whether hydrotherapy in a thermomineral institution is superior to the same hydrotherapy in an ordinary hospital exercise-bath . DESIGN Controlled therapeutic trial . SETTING The thermomineral institution at Arcen and the exercise bath at the Maasl and Hospital in Sittard , the Netherl and s. PATIENTS AND METHODS 46 patients with rheumatoid arthritis were treated in a by a skilled physiotherapist , according to a st and ardized exercise-scheme : 27 were treated in the thermomineral institution and 19 ( control-group ) in the hospital exercise-bath . Each patient received 12 treatments in 12 weeks . ENDPOINTS PARAMETERS : Morning stiffness , erythrocyte sedimentation rate , Ritchie index , amount of pain , answers to 11 questions concerning the activities of daily life , and psychosocial aspects of the disease . The various subjective and objective parameters were scored by the same physician . RESULTS Statistically significant improvement was observed in both groups concerning morning stiffness . Other subjective parameters improved , but did not reach significance . Objective parameters did not change significantly . Between-group differences were not found . CONCLUSION Hydrotherapy has a positive effect on some subjective but not on objective parameters in patients with rheumatoid arthritis , whether it is applied in a thermomineral institution or an ordinary hospital exercise bath", "OBJECTIVE To determine the effect of a low load resistance exercise training program on muscle strength , functional outcome , and cardiovascular endurance . METHODS Forty-nine patients , 37 women and 12 men between the ages of 35 - 76 yrs ( mean 60.5 yrs ) , with definite rheumatoid arthritis ( RA ) functional class II and III ( mean disease duration of 10.5 yrs ) were r and omly assigned to exercise and control groups for a 12 wk resistive muscle training program . A circuit weight bearing form of training was incorporated using light loads with high repetitions . A video tape demonstrating the exercises was given to all exercising participants to enable them to continue the program at home at least 3 times per wk with a biweekly self-report evaluation . Baseline and post-intervention evaluations included joint activity , muscle strength , endurance , functional outcome , and self-report . Cardiovascular fitness measured by treadmill time , anaerobic threshold and peak oxygen consumption ( VO2 ) in this group were assessed at baseline and 12 wks . RESULTS A significant improvement at 12 wks was noted in the exercise group for self-reported joint count ( p = 0.02 ) , number of painful joints ( p = 0.004 ) , HAQ ( p = 0.012 ) , sit-to-st and time ( p = 0.02 ) , grip strength ( p = 0.05 ) knee extension 60 degrees ( p = 0.03 ) , Arthritis Impact Measurement Scales dexterity ( p = 0.02 ) , and time to anaerobic threshold ( p = 0.03 ) . Significant improvement in the exercise group compared to the control group was noted for self-reported joint count ( p = 0.02 ) , night time pain ( p = 0.05 ) , and sit-to-st and time ( p = 0.02 ) . Increase in treadmill time was not statistically significant nor was a change in peak oxygen consumption ( VO2 ) noted . Abnormalities on initial treadmill screening were detected in 2 of 49 asymptomatic patients . They were excluded from the study and subsequent workup revealed significant coronary artery disease . CONCLUSION Low load resistive muscle training increased functional capacity as reported by patients and is a clinical ly safe form of exercise in functional class II and III RA . Screening this population for dormant coronary artery disease is recommended", "OBJECTIVE To ascertain the effectiveness of the National Arthritis Foundation ( NAF ) aquatic and on-l and exercise programs on functional fitness and perceived ability to perform activities of daily living ( ADL ) measures in older adults with arthritis . DESIGN The effects of aquatic and on-l and exercise intervention programs were analyzed by repeated- measures analysis of variance by using a planned comparison approach with an independent 3 x 2 ( group by test ) design . omega(2 ) analyses were used to ascertain the relative treatment magnitude of each dependent variable . SETTING Testing in an indoor track facility ; exercise programs conducted in community setting s. PARTICIPANTS A volunteer sample of 30 men and women with arthritis ( osteoarthritis , n=22 ; rheumatoid arthritis , n=8 ) , r and omly assigned into either an aquatic exercise ( n=10 ) , on-l and exercise ( n=10 ) , or control group ( n=10 ) . INTERVENTION Eight-week on-l and and aquatic exercise program . MAIN OUTCOME MEASURES Functional fitness , ADLs , and h and -held dynamometry measures assessed on a 1-day pretest and posttest session , before and after an 8-week exercise program . RESULTS Aquatic and on-l and exercise subjects showed significant improvements on 9 of 12 functional fitness , 3 of 4 ADLs , and 7 of 8 h and -held isometric strength tests after their respective exercise programs . No significant changes were found in any of these measures for the control group . CONCLUSION Both NAF exercise programs appear to be effective in improving functional physical fitness and perceived ability to perform ADL measures in older adults with arthritis", "The aim was to compare static and dynamic shoulder rotator endurance training in a group of women with mild rheumatoid arthritis and to see whether such training could influence impairment , disability , and h and icap . The effects on general health were also studied . Patients were r and omly assigned to a static ( n = 17 ) ( average age 59 , median disease duration 7 ) or a dynamic training group ( n = 20 ) ( average age 56 , median disease duration 10.5 ) . Measurements were taken at the start , 10 weeks later when the training period was finished , and after a further 10 weeks . After the training both groups had fewer swollen joints in the upper extremity and less shoulder-arm pain . The dynamic group patients also improved according to the physical and overall dimensions of the Sickness Impact Profile . As impairment and aspects of disability and h and icap were influenced by training but not by the patients ' opinions regarding perceived disease activity and health , these relationships must be studied further", "OBJECTIVE : To investigate the benefit of intensive dynamic exercises in comparison to range of motion ( ROM ) and isometric exercises in rheumatoid arthritis . METHODS : 100 consecutive rheumatoid arthritis patients on stable medication were r and omly assigned to ( 1 ) intensive dynamic group exercises which included full weight bearing exercises and conditioning exercises on a stationary bicycle while the heart rate was maintained at 70 - 85 % of the age predicted maximum heart rate , ( 2 ) range of motion ( ROM ) exercises and isometric exercises in a group , ( 3 ) individual isometric and ROM exercises , and ( 4 ) home instructions for isometric and ROM exercises . Variables of physical condition , muscle strength , joint mobility , daily functioning ( HAQ ) , and disease activity were assessed before and after the 12 week exercise course , and 12 weeks thereafter . An intention to treat analysis was performed . RESULTS : Increases in aerobic capacity ( n = 77 ) , muscle strength , and joint mobility in the high intensity exercise programme were respectively 17 % , 17 % and 16 % and differed significantly from the changes in aerobic capacity , muscle strength , and joint mobility in the other exercise groups . No deterioration of disease activity was observed . Twelve weeks after discontinuation of the exercise course the gain in physical capacity had disappeared . CONCLUSIONS : Intensive dynamic training is more effective in increasing aerobic capacity , joint mobility , and muscle strength than ROM exercises and isometric training in rheumatoid arthritis patients with well controlled disease", "This study aim ed at evaluating the effects of a dynamic physical training programme on circulating levels of corticotropin-releasing hormone ( CRH ) , beta-lipotropin ( beta-LPH ) , and beta-endorphin ( beta-EP ) after high-intensity training for 6 weeks ( 60 min twice a week ) and after low-intensity training ( home-training ) for another 6 months in patients with rheumatoid arthritis ( RA ) and in healthy subjects . Additionally , differences in neuropeptide levels between the two groups were studied . A total of 30 patients with RA were r and omly allocated to the study , 15 in the training group ( TG ) and 15 in the control group ( CG ) . In addition , 20 healthy subjects ( 10 in TG ; 10 in CG ) participated . In addition to the biochemical analyses , the following variables were assessed for the RA group : pain and disability ( Stanford health assessment question naire ) , joint tenderness ( Ritchie articular index ) , disease activity , muscle function , aerobic capacity , sociodemographic data and attitudes . The results obtained at the start revealed significant differences ( p CRH levels , RA patients showing the lower levels ( RA-group Md = 24 pmol/L , healthy group Md = 29 pmol/L ) . No significant differences concerning beta-LPH and beta-EP were found here . After the high-intensity training period , a significant increase of the CRH levels were found for the RA-TG ( pretest Md = 24 pmol/L , after 6 weeks Md = 27 pmol/L , p beta-EP , significant differences between the RA-TG and healthy-TG were found after the training . RA patients generally showing higher levels as compared with the healthy ( RA-group Md = 42 pmol/L , healthy group Md = 36 pmol/L , p beta-LPH levels . In conclusion , the effects of physical training on circulating neuropeptides remain still incompletely examined , and there is no definite answer to the question whether increased beta-EP levels are good or bad", "OBJECTIVE Patients with rheumatoid arthritis ( RA ) are more at risk for the development of osteoporosis and osteoporotic fractures than are their healthy peers . In this r and omized , controlled , multicenter trial , the effectiveness of a 2-year high-intensity weight-bearing exercise program ( the Rheumatoid-Arthritis- Patients -In-Training [ RAPIT ] program ) on bone mineral density ( BMD ) was compared with usual care physical therapy , and the exercise modalities associated with changes in BMD were determined . METHODS Three hundred nine patients with RA were assigned to an intervention group , either the RAPIT program or usual care physical therapy . The primary end points were BMD of the hip and spine . The exercise modalities examined were aerobic fitness , muscle strength , and , as a surrogate for those effects not directly measured by the RAPIT program , attendance rate . RESULTS The data on the 136 RAPIT participants and 145 usual care participants who completed the study were analyzed . The mean rate of decrease in hip BMD , but not in lumbar spine BMD , was smaller in patients participating in the RAPIT program when compared with that in the usual care group , with a mean decrease of 1.6 % ( 95 % confidence interval [ 95 % CI ] 0.8 - 2.5 ) over the first year and 0.5 % ( 95 % CI 1.1 - 2.0 ) over the second year . The change in hip BMD was significantly and independently associated with changes in both muscle strength ( multivariate odds ratio [ OR ] 1.75 , 95 % CI 1.07 - 2.86 ) and aerobic fitness ( OR 1.79 , 95 % CI 1.10 - 2.90 ) , but not with the attendance rate ( OR 1.00 , 95 % CI 0.99 - 1.00 ) . CONCLUSION A long-term high-intensity weight-bearing exercise program for RA patients is effective in slowing down the loss of BMD at the hip . The exercise modalities associated with this effect are muscle strength and aerobic fitness", "A group of 120 patients with rheumatoid arthritis or osteoarthritis volunteered to be subjects for this study of aerobic versus nonaerobic exercise . Patients were stratified by diagnosis and r and omized into an exercise program of aerobic walking , aerobic aquatics , or nonaerobic range of motion ( controls ) . The retention rate for the 12-week program was 83 % . Exercise tolerance , disease-related measures , and self-reported health status were assessed . The aquatics and walking exercise groups showed significant improvement over the control group in aerobic capacity , 50-foot walking time , depression , anxiety , and physical activity after the 12-week exercise program . There were no significant between-group group differences in the change scores for flexibility , number of clinical ly active joints , duration of morning stiffness , or grip strength . Our findings document the feasibility and efficacy of conditioning exercise for people who have rheumatoid arthritis or osteoarthritis", "OBJECTIVE . A Phase II trial was performed as a preliminary test of the efficacy and safety of progressive resistance training ( PRT ) as adjunct treatment for rheumatoid cachexia . METHODS Ten mildly disabled patients with well-controlled rheumatoid arthritis ( RA ) trained , on average , 2.5 times per week for 12 weeks . Ten age and sex matched RA patients with similar disease characteristics were non-r and omly assigned to a control group . Body composition , physical function , and disease activity were assessed pre and post intervention period . RESULTS Between group comparisons at followup by ANCOVA using baseline scores as covariate showed significant increases in fat-free mass ( + 1253 g , p = 0.004 ) , total body protein ( + 1063 g , p = 0.044 ) , and arm ( + 280 g , p = 0.005 ) and leg ( + 839 g , p = 0.001 ) lean mass ( a proxy measure of total body skeletal muscle mass ) in response to PRT with no exacerbation of disease activity . There was also a trend for loss of fat mass in the trunk ( -752 g , p = 0.084 ) and a significant reduction in percent body fat ( -1.1 % , p = 0.047 ) . Changes in body composition were associated with improvements in various measures of physical function . CONCLUSION Intense PRT with adequate volume seems to be an effective and safe intervention for stimulating muscle growth in patients with RA . Pending confirmation of these results in a larger r and omized controlled trial that includes patients with more active and severe disease , a similar PRT program should be included in the management of RA as adjunct treatment for cachexia", "OBJECTIVE To evaluate the impact of a 2-year home-based strength-training program on physical function in patients with early rheumatoid arthritis ( RA ) after a subsequent 3-year followup . METHODS Seventy patients with early RA were r and omized to perform either strength training ( experimental group [ EG ] ) or range-of-motion exercises ( control group [ CG ] ) . Maximal strength values were recorded by dynamometers . The Modified Disease Activity Score ( DAS28 ) , pain , Health Assessment Question naire ( HAQ ) , walking speed , and stair-climbing speed were also measured . RESULTS The maximum strength of assessed muscle groups increased by 19 - 59 % in the EG during the training period and remained at the reached level throughout the subsequent 3 years . Muscle strength improved in the CG by 1 - 31 % , but less compared with the EG . During the 2-year training period , DAS28 decreased by 50 % and 45 % and pain by 67 % and 39 % in the EG and CG , respectively . The differences in muscle strength , DAS28 , and HAQ were significantly in favor of the EG both at the 2-year and 5-year followup assessment s. CONCLUSIONS The improvements achieved during the 2-year strength-training period were sustained for 3 years in patients with early RA", "Twenty-three patients with rheumatoid arthritis ( RA ) have been given physical training for 4 to 8 years . To compare , we have had a control group of equal size and with the same disease severity . The training program consisted of home-training and for most of the patients also group-training led by a physiotherapist . During the observation period we have found a significantly less pronounced progress of X-ray changes in the joints of the active patients compared with control patients . Physiological tests and clinical parameters , including sick-pension and sick-leave , show unanimously a better disease outcome in the active group of patients . There is probably a risk of overuse or disuse of the joints in RA but we believe that it is better to be overactive rather than the reverse . As in many other diseases , the general prescription of rest in RA is not adequate", "BACKGROUND AND PURPOSE Rheumatoid arthritis frequently results in functional impairment . This study investigated the effect of a specific exercise regimen on function . METHOD A r and omized controlled assessor-blinded ( N = 36 ) compared the effect of knee extensor and flexor muscle training on pain , the timed up and go ( TUG ) test and the Health Assessment Question naire in subjects with non-acute rheumatoid arthritis . RESULTS Knee extensor and flexor muscle training increased isokinetic torques at speeds of 60 degrees/sec-1 and 120 degrees/sec-1 as measured by an isokinetic dynamometer ( p = 0.02 - 0.003 ) . The experimental group experienced a reduction in pain ( p = 0.03 ) , an improvement in TUG time ( p = 0.01 ) and in function as measured by the Health Assessment Question naire ( p = 0.04 ) . CONCLUSIONS Specific knee muscle training can be administered safely in people with non-acute rheumatoid arthritis , and may produce functional benefits", "For decades , physical training of rheumatoid arthritis (RA)- patients has been controversial , especially for patients with active disease . The aim of this study was to investigate whether RA- patients could receive graduated training without increasing the activity of the disease . In a controlled cross-over study the effect of graduated progressive training has been evaluated in 18 RA- patients with moderately active disease . The training was performed twice weekly with aerobic conditioning and strength exercises progressing to strenuous exercises over an 8-week period . The design was a crossover project with two groups obtained by minimisation . After training the patients had significantly fewer swollen joints than before . Training of the muscles acting over the swollen joints result ed in more than a 35 % decrease in the number of swollen joints . The hemoglobin level increased significantly after the training period . The erythrocyte sedimentation rate , the complement factor C3d , and the number of sore joints remained unchanged . A decrease in the need for medicine was non-significant . From this study it appears that RA- patients with some activity are trainable without aggravating the disease , even in the chronically swollen joints . The rheumatoid arthritis activity decreased with fewer swollen joints and higher hemoglobin level after training", "OBJECTIVE To study the short-term effects of physical therapy ( ice massage or wax packs , thermal baths , and faradic h and baths ) and exercise therapy on the rheumatoid h and . METHODS The effect of individual physical therapy and exercise therapy programs was evaluated in 50 r and omly selected rheumatoid arthritis in patients ( 38 women and 12 men ) . Mean patient age ( + /- SD ) was 47.94 + /- 11.22 years , and mean disease duration was 5.04 + /- 4.80 years . The control group consisted of 50 r and omly selected rheumatoid arthritis out patients ( 37 women and 13 men ; mean age 48.46 + /- 10.65 years , mean duration of disease 5.23 + /- 4.89 years ) who at the time of the investigation were not receiving any physical or exercise therapy . The clinical indices used for evaluation of inflammation included erythrocyte sedimentation rate ( ESR ) , pain intensity , proximal interphalangeal ( PIP ) joint size , and Ritchie articular index . H and grip strength , palmar tip-to-tip and key pinch finger strength , finger range of motion , and activities of daily living ( ADL ) were the parameters used to assess the functional h and status . The study was single-blinded and of 3 weeks duration . RESULTS In the physical therapy treated group , there was an improvement for most of the observed indices from baseline parameters that achieved statistical significance ( P ESR and PIP joint size improved clinical ly but failed to reach statistical significance . Patients had a more significant improvement in h and pain , joint tenderness , and ADL score ( P range of motion ( P physical and , particularly , exercise therapy produce a favorable improvement in the functional status of the rheumatoid h and", "Objective : The objective was to prospect ively evaluate the short as well as the long‐term effects of intensive physiotherapy in a stable , sunny and warm climate on physical function and health related quality of life in patients with rheumatoid arthritis ( RA ) and spondylarthropathies ( SpA ) . Methods : Ninety‐three Swedish patients with RA and SpA receiving physiotherapy for 4 weeks in Israel or Tenerife were followed for 6 months . Physical function was evaluated by the Swedish version of Stanford Health Assessment Question naire ( HAQ ) and quality of life by the Nottingham Health Profile ( NHP ) question naire . Results : There were significant improvements in HAQ‐scores and global NHP‐scores as well as all subcategories of NHP immediately after the treatment abroad , effects that were still measurable after six months . At that time point nearly half of the patients had clinical ly meaningful reduction of HAQ‐scores ( ≥0.25 ) . Conclusion : Physiotherapy in a warm and stable climate , with many hours of daily sunshine , is a valuable treatment complement for Swedish patients with RA and", "OBJECTIVE To investigate the effects of a dynamic , intensive exercise regimen on pain , disease activity , and physical functioning in active rheumatoid arthritis ( RA ) . METHODS 64 patients with RA with a mean age of 60 ( 13 ) years and mean disease duration of 8 ( 8) years , admitted to hospital because of active disease , were r and omly assigned to an intensive exercise programme or to a conservative exercise programme during their period in hospital with a mean length of 30 ( 14 ) days . The intensive exercise programme consisted of knee and shoulder dynamic and isometric muscle strengthening exercises against resistance five times a week and conditioning bicycle training three times a week and was supplemental to the conservative exercise programme of range of motion and isometric exercises . Indices of disease activity , pain , muscle strength , and functional ability were assessed at 0 , 3 , 6 , 12 , and 24 weeks by a blinded observer . RESULTS The medical treatment during the study was the same in both groups . Both groups improved in measures of disease activity , differences between groups were not statistically significant . The mean improvement in disease activity score at 24 weeks in the intensive and conservative exercise group was −1.4 ( 1.5 ) and −0.7 ( 1.4 ) , respectively . Measures of physical functioning improved significantly for patients in the intensive exercise group , and differences between groups were statistically significant for measures of muscle strength . CONCLUSION A short term intensive exercise programme in active RA is more effective in improving muscle strength than a conservative exercise programme and does not have deleterious effects on disease activity", "Sixty-seven patients with classical or definite rheumatoid arthritis ( RA ) were studied concerning the effects of st and ardized physical training on muscle function in the lower extremities . The patients were r and omly assigned to four different training groups and were given 6 weeks of training supervised by a physiotherapist at a health care centre . The groups differed according to type ( dynamic or static ) and extent ( 12 or 4 times ) of training . During this training period as well as for an additional 3 months , the patients carried out programs of exercise at home ( either dynamic or static ) . A significantly greater increase in function during the 6-week period as regards muscle strength , endurance , aerobic capacity , and functional ability was found for the dynamic as compared with the static groups . The findings at follow-up 3 months later were similar . The effectiveness of the programs did not vary with the extent of training . In conclusion , in RA patients , dynamic training gives a greater increase in physical capacity than does static training", "OBJECTIVE There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis ( RA ) . We undertook this r and omized , controlled , multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program ( Rheumatoid Arthritis Patients In Training [ RAPIT ] ) with those of physical therapy ( termed usual care [ UC ] ) . METHODS Three hundred nine RA patients were assigned to either the RAPIT program or UC . The primary end points were functional ability ( assessed by the McMaster Toronto Arthritis [ MACTAR ] Patient Preference Disability Question naire and the Health Assessment Question naire [ HAQ ] ) and the effects on radiographic progression in large joints . Secondary end points concerned emotional status and disease activity . RESULTS After 2 years , participants in the RAPIT program showed greater improvement in functional ability than participants in UC . The mean difference in change of the MACTAR Question naire score was 2.6 ( 95 % confidence interval [ 95 % CI ] 0.1 , 5.2 ) over the first year and 3.1 ( 95 % CI 0.7 , 5.5 ) over the second year . After 2 years , the mean difference in change of the HAQ score was -0.09 ( 95 % CI -0.18 , -0.01 ) . The median radiographic damage of the large joints did not increase in either group . In both groups , participants with considerable baseline damage showed slightly more progression in damage , and this was more obvious in the RAPIT group . The RAPIT program proved to be effective in improving emotional status . No detrimental effects on disease activity were found . CONCLUSION A long-term high-intensity exercise program is more effective than UC in improving functional ability of RA patients . Intensive exercise does not increase radiographic damage of the large joints , except possibly in patients with considerable baseline damage of the large joints", "OBJECTIVE To investigate whether a high-intensity exercise program accelerates the rate of radiologic damage of the large joints in predefined subgroups of patients with rheumatoid arthritis . METHODS The data of 277 participants in a 2-year r and omized controlled trial , comparing the effects of high-intensity exercises with usual care , were used . Linear regression analysis was used to test which predefined variables at baseline ( age , disease duration , disease activity , physical capacity , functional ability , joint damage ) modified the effect of high-intensity exercise on the progression of radiologic damage of the large joints over 24 months . RESULTS Baseline radiologic joint damage was the only variable associated with the effect of high-intensity exercise on joint damage progression in large joints . In a subgroup of 218 patients with no or little joint damage ( defined as Larsen score the proportions of patients with an increase in joint damage were similar for the exercise and usual-care group ( 35 % versus 36 % , risk ratio [ RR ] 1.0 [ 0.7 - 1.4 ] ; P = not significant ) , whereas , in a subgroup of 59 patients who already had extensive damage of large joints ( defined as Larsen score > 5 ) the proportion was significantly higher in the exercise group ( 85 % versus 48 % , RR 1.8 [ 1.2 - 2.6 ] ; P High-intensity weight-bearing exercises appear to accelerate joint damage progression in patients with preexisting extensive damage . Patients with extensive large joint damage should , therefore , be advised to refrain from activities excessively loading the damaged joints", "ABSTRACT Cardiorespiratory function and exercise tolerance appear very limited in persons with rheumatoid arthritis ( RA ) . Many studies have demonstrated that aerobic exercise training is beneficial to prevent physical deconditioning without inducing adverse effects on an individual 's joints and general health . The present study was conducted to demonstrate that a dance-based exercise program is a safe and efficient activity to improve physical fitness and psychological state in persons with RA . A group of 19 persons ( mean age , 49.3 ± 13 yr ) participated in a 12-wk exercise program ( twice weekly ) , whereas 10 persons ( mean age , 49.4 ± 12 yr ) served as controls . Health status , use of medication , joint pain and swelling , physical fitness , activity of daily living and psychological state were assessed at baseline , after the 12-wk training program and 6 mo after the end of the program . Exercise training induced a mean improvement of 13 % in aerobic power , with the highest values reaching 40 % . No significant changes were observed in joint status , even though the count of painful joints tended to decrease in the exercise group . Positive changes in depression , anxiety , fatigue and tension were observed after the 12-wk exercise program . These findings provide some evidence s in favor of aerobic exercise in individuals with RA . Furthermore , it is of primary interest to note that a weight-bearing activity with limited ground impacts do not provoke short-term adverse effects on joint status . Further studies , however , are required to determine the long-term effect of weight-bearing exercise on the health status of individuals with RA", "The effects of physical training on elderly , fragile patients with rheumatoid arthritis ( RA ) who are on low-dose steroids were investigated . The controlled study included 24 patients who had been treated with low-dose steroids for 2 years . Each patient was assigned either to a treatment group receiving training or to an untrained control group . The training took place over a 3-month period and was based on a protocol using progressive interval training consisting of bicycle exercises , heel lifts , and step-climbing . The exercises were performed twice weekly for 45 minutes . Comparison of the two groups showed that disease activity did not increase in the trained group and that fewer , but not significantly fewer , swollen joints were observed in this group ( p = 0.06 ) . No significant changes were noticed in erythrocyte sedimentation rate , tender joints , or morning stiffness . The work capacity of the trained patients were doubled and the numbers of repetitions increased 76 % . Individually adapted exercise programs can therefore be recommended for elderly rheumatoid arthritis patients on steroid treatment" ]	4118374a-06ff-11f0-808a-c43d1ab1c353
The role of nutritional supplementation is of increasing interest with regard to ocular disease . R and omised controlled trials have demonstrated the effectiveness of supplementation for age-related macular degeneration , and formulations are now being developed for use by people with diabetes and diabetic retinopathy . The aim of this review was to synthesis e the evidence for use of nutritional supplementation in type 2 diabetes . MEDLINE and EMBASE data bases were search ed using a systematic approach . Only double-masked r and omised controlled trials were selected . A total of 50 trials were identified as suitable for inclusion . The potential role of alpha-lipoic acid , chromium , folic acid , isoflavones , magnesium , Pycnogenol , selenium , vitamin C , vitamin E , and zinc in the treatment of type 2 diabetes is discussed . The review of trials identifies positive effects of these nutrients on various outcome measures relating to insulin resistance and cardiovascular factors . Chromium was the most studied supplement , accounting for 16 of the 50 trials . A majority of the trials found a positive effect of chromium on fasting plasma glucose . Isoflavones were found to have a positive effect on insulin resistance and cardiovascular outcome measures , but only when combined with soy proteins . Vitamin E is reported to reduce oxidative stress at levels of 200 mg day(-1 ) or more	[ "OBJECTIVE Hypomagnesemia occurs in 25–38 % of patients with type 2 diabetes . Several studies have suggested an association between magnesium ( Mg ) depletion and insulin resistance and /or reduction of insulin secretion in these cases . Our purpose was to evaluate if Mg supplementation ( as magnesium oxide [ MgO ] ) would improve metabolic control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied 128 patients with type 2 diabetes ( 32 men , 96 women , aged 30–69 years ) , treated by diet or diet plus oral antidiabetic drugs , in the Bahia Federal University Hospital , Brazil . Patients at risk for hypomagnesemia or with reduced renal function were excluded . This study was a clinical r and omized double-blind placebo-controlled trial . Patients received either placebo , 20.7 mmol MgO , or 41.4 mmol MgO daily(elementary Mg ) for 30 days . Mg concentrations were measured in plasma , in mononuclear cells , and in 24-h urine sample s. Fasting blood glucose , HbA1 , and fructosamine were used as parameters of metabolic control . RESULTS Of the patients , 47.7 % had low plasma Mg , and 31.1 % had low intramononuclear Mg levels . Intracellular Mg in patients with diabetes was significantly lower than in the normal population ( 62 blood donors ; 1.4 ± 0.6 vs. 1.7 ± 0.6 μg/mg of total proteins ) . No correlation was found between plasma and intracellular Mg concentrations ( r = −0.179 ; P = 0.15 ) or between Mg concentrations and glycemic control ( r = −0.165 ; P = 0.12 ) . Intracellular Mg levels were lower in patients with peripheral neuropathy than in those without ( 1.2 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . Similar findings were observed in patients with coronary disease ( 1.0 ± 0.5 vs. 1.5 ± 0.6 μg/mg ) . In the placebo and in the 20.7 mmol Mg groups , neither a change in plasma and intracellular levels nor an improvement in glycemic control were observed . Replacement with 41.4 mmol Mg tended to increase plasma , cellular , and urine Mg and caused a significant fall ( 4.1 ± 0.8 to 3.8 ± 0.7 mmol/1 ) in fructosamine ( normal , 1.87–2.87 mmol/1 ) . CONCLUSIONS Mg depletion is common in poorly controlled patients with type 2 diabetes , especially in those with neuropathy or coronary disease . More prolonged use of Mg in doses that are higher than usual is needed toestablish its routine or selective administration in patients with type 2 diabetes to improve control or prevent chronic complications", "Objective : To determine the effects of combined zinc ( Zn ) and chromium ( Cr ) supplementation on oxidative stress and glucose homeostasis of people with type 2 diabetes . Design : Tunisian adult subjects with HbA1C > 7.5 % were supplemented for 6 months with 30 mg/d of Zn as Zn gluconate or 400 μg/d of Cr as Cr pidolate or combined Zn/Cr supplementation or placebo . The effects of supplementation on plasma zinc ( Zn ) , copper ( Cu ) , selenium ( Se ) , urinary Zn , Cr , plasma thiobarbituric acid reactive substances ( TBARS ) , Cu-Zn superoxide dismutase ( SOD ) and Se glutathione peroxidase ( GPx ) in red blood cells , blood lipids and lipoproteins , HbA1C and fasting glucose were measured at the beginning of the study and after six months . Results : At the beginning of the study , more than 30 % of the subjects may have been Zn deficient with plasma Zn values less than 10.7 μmol/L , whereas levels of plasma Cu , Se and antioxidant RBC enzyme activities were in the normal ranges . Following supplementation , there were significant decreases of plasma TBARS in the Cr ( 13.6 % ) , Zn ( 13.6 % ) and Zn/Cr ( 18.2 % ) groups with no significant changes in the placebo group . The value for the TBARS of the control healthy Tunisian subjects was 2.08 ± 0.04 μmol/L and that of the Tunisian subjects with diabetes was 3.32 ± 0.05 μmol/L. This difference of 1.24 μmol/L between the control group and the subjects with diabetes was reduced from 36 % to 50 % in the three supplemented groups . Supplementation did not modify significantly HbA1C nor glucose homeostasis . No adverse effects of Zn supplementation were observed on Cu status , HDL cholesterol nor interactions in Zn or Cr . Conclusions : These data suggest the potential beneficial antioxidant effects of the individual and combined supplementation of Zn and Cr in people with type 2 DM . These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes", "BACKGROUND We investigated the potential effects of chromium supplementation on QTc interval duration in type 2 diabetic patients . METHODS Of 60 patients with type 2 diabetes mellitus , 30 were r and omly assigned to group A , and 30 to group B. Group A received 1000 microg of chromium picolinate ( CrPic ) daily for 3 months , followed by placebo in the next 3 months ; group B was treated with placebo for the first 3 months and CrPic in the next 3 months . At each visit , QT interval was measured on a st and ard electrocardiogram by averaging 3 consecutive beats in leads II and V4 and corrected for heart rate with Bazett formula . RESULTS Although baseline QTc interval was similar in both groups ( 422 + /- 34 milliseconds in group A vs 425 + /- 24 milliseconds in group B , P = .77 ) , QTc interval at 3 months was shorter in group A ( 406 + /- 35 milliseconds ) than in group B ( 431 + /- 26 milliseconds , P = .01 ) . In the following 3 months , QTc interval shortened in group B but not in group A , which result ed in a comparable QTc interval duration of both groups at the end of the study ( 414 + /- 28 milliseconds in group A vs 409 + /- 22 milliseconds in group B , P = .50 ) . Apart from body mass index ( 31.4 + /- 4.2 kg/m2 in patients with QTc shortening vs 28.7 + /- 4.2 kg/m2 in patients without QTc shortening , P = .03 ) , none of the clinical and laboratory variables predicted QTc interval shortening in our patient cohort . CONCLUSIONS Short-term chromium supplementation shortens QTc interval in patients with type 2 diabetes mellitus", "OBJECTIVE Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease . Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause . The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance , glycemic control , and cardiovascular risk markers in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a r and omized , double blind , cross-over trial of dietary supplementation with phytoestrogens ( soy protein 30 g/day , isoflavones 132 mg/day ) versus placebo ( cellulose 30 g/day ) for 12 weeks , separated by a 2-week washout period . RESULTS Compliance with the dietary supplementation was > 90 % for both treatment phases . When compared with the mean percentage change from baseline seen after 12 weeks of placebo , phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin ( mean + /- SD 8.09 + /- 21.9 % , P = 0.006 ) , insulin resistance ( 6.47 + /- 27.7 % , P = 0.003 ) , HbA(1c ) ( 0.64 + /- 3.19 % , P = 0.048 ) , total cholesterol ( 4.07 + /- 8.13 % , P = 0.004 ) , LDL cholesterol ( 7.09 + /- 12.7 % , P = 0.001 ) , cholesterol/HDL cholesterol ratio ( 3.89 + /- 11.7 % , P = 0.015 ) , and free thyroxine ( 2.50 + /- 8.47 % , P = 0.004 ) . No significant change occurred in HDL cholesterol , triglycerides , weight , blood pressure , creatinine , dehydroepi and rosterone sulfate , and rostenedione , and the hypothalamic-pituitary-ovarian axis hormones . CONCLUSIONS These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance , glycemic control , and serum lipoproteins in postmenopausal women with type 2 diabetes , thereby improving their cardiovascular risk profile", "Alpha-lipoic acid ( ALA ) , a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models . Clinical studies described an increase of insulin sensitivity after acute and short-term ( 10 d ) parenteral administration of ALA . The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled , multicenter pilot study to determine see whether oral treatment also improves insulin sensitivity . Seventy-four patients with type-2 diabetes were r and omized to either placebo ( n = 19 ) ; or active treatment in various doses of 600 mg once daily ( n = 19 ) , twice daily ( 1200 mg ; n = 18 ) , or thrice daily ( 1800 mg ; n = 18 ) alpha-lipoic acid . An isoglycemic glucose-clamp was done on days 0 ( pre ) and 29 ( post ) . In this explorative study , analysis was done according to the number of subjects showing an improvement of insulin sensitivity after treatment . Furthermore , the effects of active vs. placebo treatment on insulin sensitivity was compared . All four groups were comparable and had a similar degree of hyperglycemia and insulin sensitivity at baseline . When compared to placebo , significantly more subjects had an increase in insulin-stimulated glucose disposal ( MCR ) after ALA treatment in each group . As there was no dose effect seen in the three different alpha-lipoic acid groups , all subjects receiving ALA were combined in the \" active \" group and then compared to placebo . This revealed significantly different changes in MCR after treatment ( + 27 % vs. placebo ; p placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA . The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes . The encouraging findings of this pilot trial need to be substantiated by further investigations", "We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations ( 2.18 + /- 0.04 vs 1.86 + /- 0.03 mmol/L , P less than 0.01 ) in twelve aged ( 77.8 + /- 2.1 y ) vs 25 young ( 36.1 + /- 0.4 y ) , nonobese subjects . Subsequently , aged subjects were enrolled in a double-blind , r and omized , crossover study in which placebo ( for 4 wk ) and chronic magnesium administration ( CMA ) ( 4.5 g/d for 4 wk ) were provided . At the end of each treatment period an intravenous glucose tolerance test ( 0.33 g/kg body wt ) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed . CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action . Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action . In aged patients , correction of a low erythrocyte magnesium concentration may allow an improvement of glucose h and ling", "BACKGROUND Some studies have shown potential benefit of vitamin E on platelet function , but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation . Gamma-tocopherol , a major dietary form of vitamin E , may have protective properties different from those of alpha-tocopherol . OBJECTIVE We compared the effects of supplementation with alpha-tocopherol ( 500 mg ) and a gamma-tocopherol-rich compound ( 500 mg , containing 60 % gamma-tocopherol ) on serum and cellular tocopherol concentrations , urinary tocopherol metabolite excretion , and in vivo platelet activation in subjects with type 2 diabetes . DESIGN Fifty-eight subjects were r and omly assigned to receive either 500 mg alpha-tocopherol/d , 500 mg mixed tocopherols/d , or matching placebo . Serum , erythrocyte , and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention . Soluble CD40 lig and , urinary 11-dehydro-thromboxane B2 , serum thromboxane B2 , soluble P-selectin , and von Willebr and factor were measured as biomarkers of in vivo platelet activation . RESULTS Serum alpha-tocopherol increased with both tocopherol treatments . Serum and cellular gamma-tocopherol increased 4-fold ( P red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation . Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols . Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol , which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver . Neither treatment had any significant effect on markers of platelet activation . CONCLUSIONS Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol , whereas mixed tocopherols increased both serum alpha-tocopherol and serum and cellular gamma-tocopherol . Changes in serum tocopherol closely reflect changes in cellular concentrations of tocopherols after supplementation", "Ten control ( healthy ) subjects and 15 non-insulin-dependent diabetics underwent an oral glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation ( 900 mg/d for 4 mo ) . In control subjects ( placebo-treated vs vitamin E-supplemented subjects , respectively ) vitamin E reduced the area under the curve for glucose ( 344 + /- 21 vs 287 + /- 13 mmol . L-1 x min-1 ; P total body glucose disposal ( 39.0 + /- 0.3 vs 47.6 + /- 0.4 mumol.kg lean body mass-1 x min-1 ; P non-oxidative glucose metabolism ( 23.4 + /- 0.2 vs 30.8 + /- 0.3 mumol.kg lean body mass-1 x min-1 ; P vitamin E supplementation reduced glucose area under the curve ( 614 + /- 129 vs 544 + /- 98 mmol . L-1 x min-1 ; P glucose disappearance ( 19.4 + /- 0.4 vs 26.4 + /- 0.7 mumol.kg lean body mass-1.min-1 ; P total glucose disposal ( 19.0 + /- 0.7 vs 28.1 + /- 0.4 mumol.kg lean body mass-1 x min-1 ; P nonoxidative glucose metabolism ( 8.5 + /- 0.3 vs 13.9 + /- 0.3 mumol.kg lean body mass-1 x min-1 ; P vitamin E is a useful tool to reduce oxidative stress and improve insulin action", "OBJECTIVE To study the effects of supplementation with organic and inorganic chromium on glucose tolerance , serum lipids , and drug dosage in type 2 diabetes patients , in the hope of finding a better and more economical method of control . METHODS Seventy eight type 2 diabetes patients were divided r and omly into two groups and given Brewer 's yeast ( 23.3ug Cr/day ) , and CrCl3 ( 200ug Cr/day ) sequentially with placebo in between , in a double blind cross-over design of four stages , each lasting 8 weeks . At the beginning and end of each stage , subjects were weighed , their dietary data and drug dosage recorded , and blood and urine sample s were collected for analysis of glucose ( fasting and 2 hour post 75 g glucose load ) fructosamine , triglycerides , total and HDL-cholesterol , and serum and urinary chromium . RESULTS Both supplements caused a significant decrease in the means of glucose ( fasting and 2 hour post glucose load ) , fructosamine and triglycerides . The means of HDL-cholesterol , and serum and urinary chromium were all increased . The mean drug dosage decreased slightly ( and significantly in case of Glibenclamide ) after both supplements and some patients no longer required insulin . No change was noted in dietary intakes or Body Mass Index . A higher percentage of subjects responded positively to Brewer 's yeast chromium , which was retained more by the body , with effects on fructosamine , triglycerides , and HDL-cholesterol maintained in some subjects when placebo followed it , and mean urinary chromium remaining significantly higher than zero time mean . CONCLUSION Chromium supplementation gives better control of glucose and lipid variables while decreasing drug dosage in type 2 diabetes patients . A larger scale study is needed to help decide on the convenient chemical form , and dosage required to achieve optimal response", "Abstract Through the use of a double-blind cross-over investigative method , the effect of trivalent chromium supplements on blood sugar concentrations of normal and diabetic human subjects was evaluated . Four normal and 10 diabetic subjects took 50 μg . of trivalent chromium and a chromium-placebo thrice daily by mouth for 16-week periods . Chromium did not improve hyperglycemia in diabetic patients , and there was no difference in diabetic glucose tolerance measured after placebo and chromium treatment . Normal glucose tolerance was also unaffected . Despite evidence that trivalent chromium may be an essential micronutrient for maintenance of normal glucose tolerance in rats , results of this investigation do not support suggestions of a similar role in man", "The aim of this study was to determine the effect of chromium (Cr)-enriched yeast on blood glucose and insulin variables , blood lipids , and blood markers of oxidative stress in persons with type 2 diabetes mellitus ( median duration : 3.0 yr ) . Thirty-six subjects ( 9 men , 27 women ; mean age : 61.3 yr ; mean body mass index : 34.33 kg/m2 ) were supplemented with 400 μg Cr/d as Cr-enriched yeast ( n=19 ) or placebo ( n=17 ) for 12 wk in a r and omized , double-blind study . The most interesting results were obtained by comparison of the change in the placebo group to the change in the Cr group . The Cr group showed a significantly greater increase in serum Cr compared to the placebo group ( p decrease in fasting serum glucose compared to placebo ( p ) . Blood markers of oxidative stress glutathione peroxidase activity and levels of reduced glutathione were essentially unchanged in the Cr group after 12 wk , but decreased significantly in the placebo group ( p respectively ) , Serum HbA1c and glycated protein ( fructosamine ) were essentially unchanged in the Cr group , whereas HbA1c tended to increase in the placebo group ( from 6.94 % to 7.11 % ) . Fasting serum insulin decreased in both groups , with a greater tendency in the Cr group ( −16.5 % vs −9.5 % ) . These data suggest that supplementation of well-controlled type 2 diabetics with Cr-enriched yeast is safe and can result in improvements in blood glucose variables and oxidative stress", "Abstract —Experimental evidence suggests that acute parenteral administration of high-dose ascorbic acid has beneficial vascular effects in type 2 diabetes . We studied the hemodynamic effects of chronic oral supplementation in this condition . Thirty patients , 45 to 70 years of age , with type 2 diabetes , were r and omly assigned in a double-blind manner to receive 500 mg ascorbic acid daily by mouth or placebo . Patients were studied at baseline and after 4 weeks of assigned treatment . The central aortic augmentation index ( AgIx ) and the time to wave reflection ( Tr ) were derived from radial artery pulse wave analysis data . AgIx and Tr were used as measures of systemic arterial stiffness and aortic stiffness , respectively . Ascorbic acid decreased brachial systolic blood pressure from 142.1±12.6 ( SD ) to 132.3±12.1 mm Hg ( difference [ 95 % CI ] 9.9 [ 4.7 , 15.0];P from 83.9±4.8 to 79.5±6.0 mm Hg ( 4.4 [ 1.8 , 7.0];P and AgIx from 26.8±5.5 % to 22.5±6.8 % ( 4.3 [ 1.5 , 7.1];P Tr increased from 137.1±12.6 to 143.4±9.2 ms ( −6.3 [ −10.1 , −2.5];P 0.01 ) . Placebo had no hemodynamic effects , and this difference between treatments was significant ( P oral ascorbic acid lowered arterial blood pressure and improved arterial stiffness in patients with type 2 diabetes . As strict control of blood pressure reduces cardiovascular risk in diabetes , ascorbic acid supplementation may potentially be a useful and inexpensive adjunctive therapy . Larger and longer studies now need to be performed", "This triple-blind , placebo-controlled clinical trial was conducted to determine the effect of the vitamin E on fasting blood sugar ( FBS ) , serum insulin , and glycated hemoglobin ( GHb ) in type 11 diabetic patients ( NIDDM ) . A total of 100 patients , with no complications , aged 20 - 60 years old were chosen from those consulting the Isfahan Social Security Service Diabetes Clinic and divided r and omly into two treated and placebo groups , and matched for age , sex , level of education , and occupation . The treated and placebo groups were given vitamin E tablets ( 200 IU/day ) and placebo respectively . Serum vitamin E , total cholesterol ( TC ) , triglycerides ( TG ) , FBS , insulin , and GHb were measured at the beginning and at the end of the study ( a period of 27 weeks ) ; FBS , GHb and insulin levels were also determined several times during the period . Blood lipids and FBS were measured using the ELAN 2000 autoanalyzer at the Isfahan Cardiovascular Research Center , while for measuring insulin the enzyme-linked immunosorbent assay ( ELISA ) method was used ; GHb was determined calorimetrically ( thiobarbituric acid ) , and for vitamin E measurements the Hansen and Warwick method was used , by which the vitamin E was determined fluorometrically . The findings of this study show no effect of vitamin E supplementation in the patients : GHb did not change appreciably , FBS was reduced nonsignificantly ( -4.3 % in the treated group vs. -14.0 % in the placebo group , p insulin , no increase was seen ; instead , a decrease was observed ( slightly more than 17 % in the two groups , p = 0.15 ) . No changes were observed in the levels of blood lipids . It was concluded that a daily vitamin E supplement of 200 IU for a period of 27 weeks does not affect insulin , GHb , or FBS in type II diabetic patients . However , since this antioxidant vitamin is beneficial in other ways in these patients , it would seem justified to recommend its use . Certainly , more extensive research is necessary to draw definite conclusions", "Atherosclerosis is associated with stiffening of conduit arteries and increased platelet activation , partly as a result of reduced bioavailability of nitric oxide ( NO ) , a mediator that normally has a variety of protective effects on blood vessels and platelets . Increased levels of oxygen free radicals are a feature of atherosclerosis that contributes to reduced NO bioavailability and might lead to increased arterial stiffness and platelet activation . Vitamin C is a dietary antioxidant that inactivates oxygen free radicals . This placebo-controlled , double-blind , r and omized study was design ed to establish whether acute oral administration of vitamin C ( 2 g ) , would reduce arterial stiffness and in vitro platelet aggregation in healthy male volunteers . Plasma vitamin C concentrations increased from 42+/-8 to 104+/-8 microM at 6 h after oral administration , and were associated with a significant reduction in augmentation index , a measure of arterial stiffness ( by 9.6+/-3.0 % ; p = 0.016 ) , and ADP-induced platelet aggregation ( by 35+/-13 % ; p = 0.046 ) . There was no change in these parameters after placebo . Vitamin C , therefore , appears to have beneficial effects , even in healthy subjects . The mechanism responsible is likely to involve protection of NO from inactivation by oxygen free radicals , but this requires confirmation . If similar effects are observed in patients with atherosclerosis or risk factors , vitamin C supplementation might prove an effective therapy in cardiovascular disease", "Manifestations of vascular disease , including microvascular changes , constitute the major part of the morbidity and mortality in diabetic patients . Oxidative stress has been suggested to play an important role in the vascular dysfunction of diabetic patients . Furthermore , epidemiological observations indicate a beneficial effect of an increased dietary intake of antioxidants . The present study tested the hypothesis that the antioxidant ascorbic acid influences microcirculatory function in patients with Type II diabetes . Patients with Type II diabetes were treated with 1 g of ascorbic acid three times a day for 2 weeks in a r and omized placebo-controlled double-blind cross-over design . Microvascular reactivity was assessed by vital capillaroscopy and PRH ( post-occlusive reactive hyperaemia ) . hs-CRP ( high-sensitivity C-reactive protein ) , IL-6 ( interleukin-6 ) , IL-1ra ( interleukin-1 receptor antagonist ) and ox-LDL ( oxidized low-density lipoprotein ) were analysed . The results showed no significant change in microvascular reactivity assessed after 2 weeks of ascorbic acid treatment . TtP ( time to peak ) was 12.0+/-3.3 s before and 11.2+/-3.5 s after ascorbic acid ( n=17 ) . In comparison , TtP was 11.5+/-2.9 s before and 10.6+/-2.8 s after placebo ( not significant ) . IL-1ra , IL-6 , hs-CRP and ox-LDL did not change significantly after ascorbic acid , neither as absolute or relative values . In conclusion , in contrast with some studies reported previously , we could not demonstrate an effect of continuous oral treatment with ascorbic acid on microvascular reactivity assessed at the level of individual capillaries . Furthermore , we found no indication of an effect on inflammatory cytokines or ox-LDL", "Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism . The chromium requirement is postulated to increase with increased glucose intolerance and diabetes . The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes . Individuals being treated for type 2 diabetes ( 180 men and women ) were divided r and omly into three groups and supplemented with : 1 ) placebo , 2 ) 1.92 μmol ( 100 μg ) Cr as chromium picolinate two times per day , or 3 ) 9.6 μmol ( 500 μg ) Cr two times per day . Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits . HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol ( 1,000 pg ) Cr per day and was lower in both chromium groups after 4 months ( placebo , 8.5 ± 0.2 % ; 3.85 pmol Cr , 7.5 ± 0.2 % ; 19.2 pmol Cr , 6.6 ± 0.1 % ) . Fasting glucose was lower in the 19.2-μmol group after 2 and 4 months ( 4-month values : placebo , 8.8 ± 0.3 mmol/1 ; 19.2 μmol Cr , 7.1 ± 0.2 mmol/1 ) . Two-hour glucose values were also significantly lower for the subjects consuming 19.2 μmol supplemental Cr after both 2 and 4 months ( 4-month values : placebo , 12.3 ± 0.4 mmol/1 ; 19.2 μmol Cr , 10.5 ± 0.2 mmol/1 ) . Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months . Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 μmol/day Cr . These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c , glucose , insulin , and cholesterol variables in subjects with type 2 diabetes . The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake", "Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress . Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal . Thus endothelial dysfunction may worsen insulin resistance . Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes . In the present study , we investigated effects of high-dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes . Plasma vitamin C levels in 109 diabetic subjects were lower than healthy ( 36 + /- 2 microM ) levels . Thirty-two diabetic subjects with low plasma vitamin C ( were subsequently enrolled in a r and omized , double-blind , placebo-controlled study of vitamin C ( 800 mg/day for 4 wk ) . Insulin sensitivity ( determined by glucose clamp ) and forearm blood flow in response to ACh , sodium nitroprusside ( SNP ) , or insulin ( determined by plethysmography ) were assessed before and after 4 wk of treatment . In the placebo group ( n = 17 subjects ) , plasma vitamin C ( 22 + /- 3 microM ) , fasting glucose ( 159 + /- 12 mg/dl ) , insulin ( 19 + /- 7 microU/ml ) , and SI(Clamp ) [ 2.06 + /- 0.29 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] did not change significantly after placebo treatment . In the vitamin C group ( n = 15 subjects ) , basal plasma vitamin C ( 23 + /- 2 microM ) increased to 48 + /- 6 microM ( P 80 microM ) . No significant changes in fasting glucose ( 156 + /- 11 mg/dl ) , insulin ( 14 + /- 2 microU/ml ) , SI(Clamp ) [ 2.71 + /- 0.46 x 10(-4 ) dl x kg(-1 ) x min(-1)/(microU/ml ) ] , or forearm blood flow in response to ACh , SNP , or insulin were observed after vitamin C treatment . We conclude that high-dose oral vitamin C therapy , result ing in incomplete replenishment of vitamin C levels , is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes", "BACKGROUND Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes . These abnormalities might be secondary to increased plasma concentrations of homocysteine . We sought to determine whether oral folic acid supplementation , by lowering homocysteine levels , enhanced endothelial function and reduced arterial stiffness in type 2 diabetes . METHODS Twenty-six type 2 diabetic patients ( age 56.5 + /- 0.9 years , diabetes duration 5.5 + /- 0.6 years , means + /- SEM ) with no history of cardiovascular disease received 5 mg/d of oral folic acid or placebo for 4 weeks in a double-blind , r and omized controlled , parallel group trial . The following parameters were measured before and after treatment : 1 ) endothelial function ( forearm arterial blood flow during local intra-arterial administration of endothelium-dependent [ acetylcholine 1.5 , 4.5 , and 15 microg/min ] and endothelium-independent [ sodium nitroprusside 1 , 2 , and 4 microg/min ] vasodilators ) ; and 2 ) carotid-radial and carotid-femoral pulse wave velocity . RESULTS Folic acid reduced plasma homocysteine concentrations and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate ( mean and 95 % confidence interval post versus pretreatment differences in forearm arterial blood flow ratio between the infused and control arm + 0.19 ( 0.03 - 0.35 ) , P Endothelium-independent vasodilatation and pulse wave velocity were not affected . No significant changes in forearm arterial blood flow and pulse wave velocity were observed in the placebo group . Multiple regression analysis showed that changes in folic acid , but not homocysteine , concentrations independently described changes in maximal endothelium-dependent vasodilatation . CONCLUSIONS Short-term oral folic acid supplementation significantly enhances endothelial function in type 2 diabetic patients , independent of homocysteine lowering", "OBJECTIVE Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific population s of patients with type 2 diabetes . The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes . RESEARCH DESIGN AND METHODS In this 6-month double-blind study , patients with an HbA(1c ) ( A1C ) > 8 % and insulin requirements of > 50 units/day were r and omly assigned to receive treatment with placebo or 500 or 1,000 mug chromium daily in the form of chromium picolinate . The primary efficacy parameter was a change in A1C . Secondary end points were changes in lipid profile , BMI , blood pressure , and insulin requirements . RESULTS In this per- protocol analysis ( n = 46 ) , the decrease in A1C was approximately equal across the three groups ( 0.4 % ) . All patients had a BMI > 25 kg/m(2 ) . No differences were found in the secondary end points . We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile . CONCLUSIONS There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes", "OBJECTIVE The role of selenium in preventing cardiovascular diseases has been largely described . Oxidative stress and the subsequent activation of nuclear factor-kappa B ( NF-kappaB ) have been linked to the development of vascular complications . We investigated the effects of selenium supplementation in type 2 diabetic patients on several oxidative stress parameters and NF-kappaB activity . METHODS We enrolled 56 type 2 diabetic patients with similar glycaemic control : 21 were supplemented by selenium ( 960 micro g d(-1 ) , 3 months ) and 27 received a placebo , and 10 nondiabetic subjects formed the control group . To determine NF-kappaB activation , we used an electrophoretic mobility shift assay followed by a semi-quantitative determination of NF-kappaB in peripheral blood mononuclear cells . RESULTS Selenium treatment result ed in a significant increase in plasma selenium and red-cell Se GSH px activity . It had no effect on lipid peroxidation measured by malone-dialdehyde ( MDA ) or on red-cell Cu/Zn SOD . NF-kappaB activity was increased by 80 % in diabetic patients . In patients receiving selenium supplementation , selenium NF-kappaB activity was significantly reduced , reaching the same level as the nondiabetic control group . CONCLUSION In type 2 diabetic patients , activation of NF-kappaB measured in peripheral blood monocytes can be reduced by selenium supplementation , confirming its importance in the prevention of cardiovascular diseases", "AIMS Vascular endothelial dysfunction , an early marker of atherosclerosis , has been demonstrated in Type 2 diabetes mellitus ( DM ) . Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk . We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM . METHODS Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent ( sodium nitroprusside ) and dependent ( acetylcholine , bradykinin ) vasodilators . Those with diabetes received 1600 i.u . daily oral alpha-tocopherol or placebo , double-blind for 8 weeks , and had endothelial function reassessed . RESULTS The diabetic group had higher HbA1c ( 6.9+/-1.4 vs 4.8+/-0.6 % ; P systolic ( 145+/-15 vs. 130+/-16 mm Hg ; P diastolic blood pressure ( 79+/-8 vs. 76+/-9 mm Hg ; P = 0.15 ) . There was blunted vasodilation to acetylcholine ( 15 microg/min ; P Vasodilation to sodium nitroprusside and bradykinin was similar ( all P>0.1 ) . Alpha-tocopherol did not affect vasodilation to nitroprusside ( P>0.1 ) , acetylcholine ( P>0.1 ) or bradykinin ( P>0.1 ) . CONCLUSIONS There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM . This is not improved by treatment with alpha-tocopherol", "Renal accumulation of advanced glycation end products ( AGEs ) has been linked to the progression of diabetic nephropathy . Cleavage of pre-formed AGEs within the kidney by a cross-link breaker , such as ALT-711 , may confer renoprotection in diabetes . STZ diabetic rats were r and omized into a ) no treatment ( D ) ; b ) treatment with the AGE cross-link breaker , ALT-711 , weeks 16 - 32 ( DALT early ) ; and c ) ALT-711 , weeks 24 - 32 ( DALT late ) . Treatment with ALT-711 result ed in a significant reduction in diabetes-induced serum and renal AGE peptide fluorescence , associated with decreases in renal carboxymethyllysine and RAGE immunostaining . Cross-linking of tail tendon collagen seen in diabetic groups was attenuated only by 16 weeks of ALT-711 treatment . ALT-711 , independent of treatment duration , retarded albumin excretion rate ( AER ) , reduced blood pressure , and renal hypertrophy . It also reduced diabetes-induced increases in gene expression of transforming growth factor beta1 ( TGF-beta1 ) , connective tissue growth factor ( CTGF ) , and collagen IV . However , glomerulosclerotic index , tubulointerstitial area , total renal collagen , nitrotyrosine , protein expression of collagen IV , and TGF-beta1 only showed improvement with early ALT treatment alone . This study demonstrates the utility of a cross-link breaker as a treatment for diabetic nephropathy and describes effects not only on renal AGEs but on putative mediators of renal injury , such as prosclerotic cytokines and oxidative stress", "Epidemiologic studies have correlated fasting and postload insulin levels with the risk of coronary heart disease , assuming that insulin levels are reliable markers of insulin resistance . However , this assumption has not been systematic ally studied . The author measured insulin response to an oral glucose load and quantitated insulin resistance using the euglycemic hyperinsulinemic clamp technique to evaluate the correlation between insulin level and the degree of insulin resistance in individuals with varying degrees of glucose tolerance . Subjects were r and omly selected from previous population studies done in 1987 - 1989 at the Department of Medicine of the University of Kuopio in east Finl and . Altogether , 50 subjects with normal glucose tolerance , 28 with impaired glucose tolerance , and 54 with non-insulin-dependent diabetes mellitus were studied . Correlations of insulin resistance ( whole-body glucose uptake in clamp studies ) with fasting or postload insulin levels were remarkably consistent , ranging from -0.58 to -0.74 ( p fasting insulin level correlated significantly with insulin resistance ( -0.47 , p fasting insulin level should be used as a marker of insulin resistance , particularly in subjects with abnormal glucose tolerance", "Type II diabetes is characterized by increased oxidative stress , endothelial dysfunction and hypertension . We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes . Subjects ( n = 35 ) received vitamin C ( 1.5 g daily in three doses ) or matching placebo for 3 weeks in a r and omized , double-blind , parallel-group design . Plasma concentrations of 8-epi-prostagl and in F(2alpha ) ( 8-epi-PGF(2alpha ) ) , a non-enzymically derived oxidation product of arachidonic acid , were used as a marker of oxidative stress . Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine ( with nitroprusside as an endothelium-independent control ) and by the pulse wave responses to systemic albuterol ( endothelium-dependent vasodilator ) and glyceryl trinitrate ( endothelium-independent vasodilator ) . Plasma concentrations of vitamin C increased from 58+/-6 to 122+/-10 micromol/l after vitamin C , but 8-epi-PGF(2alpha ) levels ( baseline , 95+/-4 pg/l ; after treatment , 99+/-5 pg/l ) , blood pressure ( baseline , 141+/-5/80+/-2 mmHg ; after treatment , 141+/-5/81+/-3 mmHg ) and endothelial function , as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine , were not significantly different from baseline or placebo . Thus treatment with vitamin C ( 1.5 g daily ) for 3 weeks does not significantly improve oxidative stress , blood pressure or endothelial function in patients with Type II diabetes", "A double-blind , placebo-controlled , r and omized , multi-center study was performed with 77 diabetes type II patients to investigate anti-diabetic effects of the French maritime pine bark extract , Pynogenol . Supplementation with 100 mg Pycnogenol for 12 weeks , during which a st and ard anti-diabetic treatment was continued , significantly lowered plasma glucose levels as compared to placebo . HbA1(c ) was also lowered ; however , the difference as compared to placebo was statistically significant only for the first month . In the Pycnogenol-group endothelin-1 was significantly decreased , while 6-ketoprostagl and in F(1a ) in plasma was elevated compared to placebo . Nitric oxide levels in plasma increased during treatment in both groups , but , differences did not reach statistical significance . Pycnogenol was well-tolerated with ECG , electrolytes , creatinine and blood urea nitrogen remaining unchanged in both groups . Mild and transient unwanted effects were reported for both groups without significant differences . Supplementation of Pycnogenol to conventional diabetes treatment lowers glucose levels and improves endothelial function", "Objective Oxidative stress has been suggested to play a role in the development of diabetes , hypertension and vascular dysfunction . Vitamin E , a major lipid-soluble dietary antioxidant , has two major dietary forms , α-tocopherol and γ-tocopherol . The potential importance of γ-tocopherol has largely been overlooked . Our aim was to investigate the effect of α-tocopherol and γ-tocopherol supplementation on 24-h ambulatory blood pressure ( BP ) and heart rate , vascular function and oxidative stress in individuals with type 2 diabetes . Method Fifty-eight individuals with type 2 diabetes were r and omized in a double-blind , placebo-controlled trial . Participants were r and omized to a daily dose of 500 mg/day RRR-α-tocopherol , 500 mg/day mixed tocopherols ( 60 % γ-tocopherol ) or placebo for 6 weeks . Primary endpoints were 24-h ambulatory BP and heart rate , endothelium-dependent and independent vasodilation and plasma and urinary F2-isoprostanes . Results Treatment with α-tocopherol significantly increased systolic BP [ 7.0 ( 5.2 , 8.8 ) mmHg , P [ 5.3 ( 4.0 , 6.5 ) mmHg , P 0.0001 ] , pulse pressure [ 1.8 ( 0.6 , 3.0 ) mmHg , P Treatment with mixed tocopherols significantly increased systolic BP [ 6.8 ( 4.9 , 8.6 ) mmHg , P BP [ 3.6 ( 2.3 , 4.9 ) mmHg , P [ 3.2 ( 2.0 , 4.4 ) mmHg , P 0.0001 ] and heart rate [ 1.8 ( 0.5 , 3.2 ) bpm , P Treatment with α-tocopherol or mixed tocopherols significantly reduced plasma F2-isoprostanes versus placebo , but had no effect on urinary F2-isoprostanes . Endothelium-dependent and independent vasodilation was not affected by either treatment . Conclusion In contrast to our initial hypothesis , treatment with either α- or mixed tocopherols significantly increased BP , pulse pressure and heart rate in individuals with type 2 diabetes", "OBJECTIVE To investigate the effect of chromium picolinate supplementation on the lipid profile of the predominantly Hispanic population of non-insulin-dependent diabetes mellitus ( NIDDM ) patients in San Antonio , Texas . RESEARCH DESIGN AND METHODS A prospect i ve , double-blind , placebo-controlled , crossover study was performed on 14 men and 16 women . Initially , each patient was r and omly assigned to receive either chromium picolinate or placebo for 2 months . This initial treatment phase was followed by a 2-month washout period . Subjects were then crossed-over and received the alternate capsule for an additional 2 months . Fasting blood glucose , HbA1c , and serum lipids were compared at the end of each treatment phase . RESULTS Twenty-eight of the originally enrolled 30 patients completed the study . There were no adverse reactions to chromium reported . There were no differences noted between the control and chromium-treated subjects in glucose control , high-density lipoprotein cholesterol levels , or low-density lipoprotein cholesterol levels . Triglyceride ( TG ) levels were reduced significantly ( 17.4 % ; P chromium supplementation . CONCLUSIONS Ours is the first report of a significant reduction in serum TGs in a group of NIDDM patients treated with chromium . The low cost and excellent safety profile of chromium make it an attractive lipid-lowering agent for this population . Long-term studies are needed to determine if the short-term changes in plasma lipids can be sustained", "Tocopherol has been shown to have antiplatelet effects in insulin-dependent diabetes mellitus . However , its antiplatelet effect in non-insulin-dependent diabetes mellitus ( NIDDM ) remains to be established . In this report , the antiplatelet effect of tocopherol was assessed in a r and omized , double-blind and crossover study of 15 NIDDM subjects . Each subject received tocopherol ( dl-alpha-tocopherol nicotinate , 200 mg , tid ) and a placebo for two six-week treatment periods separated by a three-week period in between for wash-out . The mechanisms of the antiplatelet effect of tocopherol were also studied in vitro . A significant decrease in platelet reactivity was observed after tocopherol treatment as compared with the pretest , and the magnitude of the decrease during tocopherol treatment was significantly evident when compared with that of the placebo treatment , as assessed by collagen ( 5 , 10 micrograms/mL)-induced platelet aggregation of whole blood . A dose-dependent reduction in both ADP- and collagen-induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in vitro . No corresponding changes in ATP secretion and thromboxane synthesis were observed . Tocopherol also significantly inhibited fibrinogen-induced aggregation of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that platelet aggregation of whole blood ex vivo , among 15 NIDDM subjects was suppressed in tocopherol treatment , so tocopherol may have an antiplatelet effect in NIDDM subjects . The inhibitory effect of the platelet aggregation of tocopherol may be partially accomplished through interference with fibrinogen binding towards its receptor", "OBJECTIVE To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein ( LDL ) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus ( NIDDM ) . RESEARCH DESIGN AND METHODS Twenty-one men with NIDDM ( HbA1c = 6 - 10 % ) , ages 50–70 , were r and omly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period . LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy . Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation ( lag time ) and formation of thiobarbituric acid-reactive substances ( TBARS ) . Fasting serum glucose , mean weekly blood glucose , HbA1c , and glycated plasma protein concentrations were also determined at these time points . RESULTS Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold , respectively , in the vitamin E-treated group . Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo ( lag time , 243 ± 46 vs. 151 ± 22 min , P ) . Vitamin E content also increased significantly in both buoyant and dense LDL subfractions , and their oxidation was dramatically reduced . The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions ( r = 0.69–0.92 ) . Glycemic indexes did not change significantly in either group during the study . Protein glycation , including glycated hemoglobin , glycated albumin , glycated total plasma proteins , and glycated LDL were unchanged in the vitamin E group . CONCLUSIONS Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation . Despite a greater percentage increase in vitamin E content in small dense LDL , it remained substantially more susceptible to oxidation than was buoyant LDL . This suggests that dense , LDL may gain less protection against oxidation from antioxidant supplementation than does larger , more buoyant LDL . In contrast to previous reports , vitamin E supplementation did not reduce glycation of intracellular or plasma proteins", "OBJECTIVE Diabetic hyperglycemia promotes sorbitol production from glucose via aldose reductase . Since the intracellular accumulation of sorbitol , or its sequelae , are postulated to contribute to the progression of chronic diabetic complications , aldose reductase inhibitors ( ARI ) offer therapeutic promise . Others have shown that vitamin C at pharmacologic doses decreases erythrocyte ( RBC ) sorbitol . We examined whether smaller , physiologic doses of vitamin C were also effective in individuals with insulin-dependent diabetes mellitus ( IDDM ) and whether vitamin C was an ARI in vitro . METHODS Vitamin C supplements ( 100 or 600 mg ) were taken daily for 58 days by young adults with IDDM and nondiabetic adults in an otherwise free-living design . Diabetic control was monitored by fasting plasma glucose , glycosylated hemoglobin , and glycosuria and was moderate to poor throughout the study . RBC sorbitol was measured at baseline and again at 30 and 58 days . Three-day dietary records and 24-hour urine collection s were performed for each sampling day . RESULTS RBC sorbitol levels were significantly elevated in IDDMs , on average doubled , despite their more than adequate dietary intakes of vitamin C and normal plasma concentrations . Vitamin C supplementation at either dose normalized the RBC sorbitol in IDDMs within 30 days . This correction of sorbitol accumulation was independent of changes in diabetic control . Furthermore , our in vitro studies show that ascorbic acid inhibited aldose reductase activity . CONCLUSIONS Vitamin C supplementation is effective in reducing sorbitol accumulation in the erythrocytes of diabetics . Given its tissue distribution and low toxicity , we suggest a superiority for vitamin C over pharmaceutic ARIs", "In order to confirm the effect of ascorbic acid ( AA ) on human erythrocyte sorbitol accumulation and explore its mechanism of action , the effects of ascorbic acid in vitro on the sorbitol ( S ) and glucose ( EG ) content of human erythrocytes and in particular on the S/EG ratio as a marker of aldose reductase ( AR ) activity were carefully observed . The results showed that both the accumulation of erythrocyte sorbitol and the S/EG ratio were strongly reduced by the addition of AA . The sorbitol content in the erythrocyte and the S/EG ratio were reduced by a maximum of 87.3 % and 83.4 % and 93.8 % and 63.9 % when the medium 's AA concentration was at its peak with 5.6 mmol/l and 28 mmol/l glucose in the medium , respectively . The contents of erythrocyte glucose measured coincidentally revealed a positive correlation with the ascorbic acid concentration in the medium during incubation in 5.6 mmol/l glucose while at a higher glucose level ( 28 mmol/l ) in the medium the correlation became negative . These results suggested that the polyol pathway could be inhibited effectively by AA through its direct action on AR . The results of a double-blind cross-over trial using AA tablets or inositol tablets in eight diabetic patients showed that the supplementation of 1000 mg AA/day for 2 weeks result ed in reductions of 12.2 % and 21.8 % in erythrocyte sorbitol and red cell sorbitol/plasma glucose ( S/PG ) ratio , respectively ( P 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Vitamin E isomers may protect against atherosclerosis . The aim of this study was to compare the effects of supplementation with either alpha-tocopherol ( alphaT ) or mixed tocopherols rich in gamma-tocopherol ( gammaT ) on markers of oxidative stress and inflammation in patients with type 2 diabetes . METHODS In a double-blind , placebo-controlled trial , 55 patients with type 2 diabetes were r and omly assigned to receive ( 500 mg/day ) ( a ) alphaT , ( b ) mixed tocopherols , or ( c ) placebo for 6 weeks . Cellular tocopherols , plasma and urine F(2)-isoprostanes , erythrocyte antioxidant enzyme activities , plasma inflammatory markers , and ex vivo assessment of eicosanoid synthesis were analyzed pre- and postsupplementation . RESULTS Neutrophil alphaT and gammaT increased ( both P tocopherol supplementation , whereas alphaT ( P gammaT decreased ( P tocopherol supplementation result ed in reduced plasma F(2)-isoprostanes ( P 24-h urinary F(2)-isoprostanes or erythrocyte antioxidant enzyme activities . Neither alphaT nor mixed tocopherol supplementation affected plasma C-reactive protein , interleukin 6 , tumor necrosis factor-alpha , or monocyte chemoattractant protein-1 . Stimulated neutrophil leukotriene B(4 ) production decreased significantly in the mixed tocopherol group ( P = 0.02 ) but not in the alphaT group ( P = 0.15 ) . CONCLUSIONS The ability of tocopherols to reduce systemic oxidative stress suggests potential benefits of vitamin E supplementation in patients with type 2 diabetes . In population s with well-controlled type 2 diabetes , supplementation with either alphaT or mixed tocopherols rich in gammaT is unlikely to confer further benefits in reducing inflammation", "The aim of this study is to evaluate the effect and safety of chromium-containing milk powder in patients with type 2 diabetes mellitus . A r and omized , double-blind , placebo-controlled trial was conducted in Taiwan . A total of 60 patients with type 2 diabetes mellitus , aged 30 to 75 years , and on a dose of gliclazide sulfonylurea agent ( Their glycosylated hemoglobin ranged from 7.5 % to 12 % , fasting plasma glucose ( FPG ) from 140 to 250 mg/dL , and body mass index from 20 to 35 kg/m(2 ) . The subjects were divided into 2 groups , one group to receive chromium-containing milk powder ( chromium 200 microg/20 g milk powder ) and the other to receive placebo twice a day for 16 weeks . Frequently sample d intravenous glucose tolerance test ( IVGTT ) was performed before and after treatment . The chromium group demonstrated a lower FPG and fasting insulin ( -38.1 + /- 9.2 vs 63 + /- 8 . 5 mg/dL and -1.7 + /- 0.2 vs 1.9 + /- 0.3 microU/mL , respectively ; P Lower glycosylated hemoglobin was observed in chromium-treated male patients ( -1.1 + /- 0 . 5 vs 0.7 + /- 0 . 2 ; P metabolic parameters ( lipid profiles including total cholesterol , triglyceride , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol ) , except improvement of insulin resistance ( homeostasis model assessment for insulin resistance and insulin sensitivity index from frequently sample d intravenous glucose tolerance test ) observed in male patients ( -2.1 + /- 1.1 vs -0.41 + /- 1.12 and 0.18 + /- 0.11 vs -0.15 + /- 0 . 2 , respectively ; P adverse events in both groups , except for mild complaints in the chromium group on constipation ( 5 % ) and flatulence ( 5 % ) . Intake of milk powder containing 400 microg/d of chromium for 16 weeks in subjects with type 2 diabetes mellitus result ed in lowering of FPG , fasting insulin , and improvement of metabolic control in male patients", "Macular degeneration associated with age and drusen , an important cause of severe visual loss in older persons , is of unknown cause . The sensory retina and retinal pigment epithelium , which are cell layers in zinc , appear to be prominently involved in the disease process . Because zinc plays a role in the metabolic function of several important enzymes in the chorioretinal complex , we undertook a prospect i ve , r and omized , double-masked , placebo-controlled investigation of the effects of oral zinc administration on the visual acuity outcome in 151 subjects with drusen or macular degeneration . Although some eyes in the zinc-treated group lost vision , this group had significantly less visual loss than the placebo group after a follow-up of 12 to 24 months . This is the first controlled oral intervention study to show a positive , if limited , treatment effect in macular degeneration , a major public health problem . Because of the pilot nature of the study and the possible toxic effects and complications of oral zinc administration , widespread use of zinc in macular degeneration is not now warranted", "Our investigations carried out in patients with diabetes mellitus revealed oxidative stress loads . The study presented here was to clarify whether a therapy with antioxidants can contribute to an improvement of prognosis . 80 patients affected with a long term diabetic late syndrome were r and omised and arranged to 4 groups of n = 20 each . In contrast to a control group these patients received 600 mg of alpha lipoic acid or 100 micrograms of selenium ( sodium selenite ) daily or 1200 IE of D-alpha-tocopherol respectively for a time of 3 months . In comparison with the control group all groups treated in an antioxidative way showed significantly diminished serum concentrations of thiobarbituric acid reactive substances and of urinary albumin excretion rates . The symptoms of distal symmetric neuropathy measured according to the thermo- and vibration sensitivity also improved in a highly significant manner . The results prove that oxidative stress plays a promoting role in developing of long term diabetic late complications and that a therapy with adjuvant antioxidants may lead to a regression of diabetic late complications", "The effect of magnesium ( Mg ) and ascorbic acid ( AA ) supplementation on metabolic control was assessed in 56 outpatient diabetics . A 90-day run-in period was followed by two 90-day treatment periods , during which Mg ( 600 mg/day ) and AA ( 2 g/day ) were administered in a r and omized double-blind cross-over fashion . A decrease in systolic and diastolic blood pressure ( 132 + /- 3 vs. 138 + /- 4 and 77 + /- 2 vs. 82 + /- 2 mm Hg ; p insulin-dependent diabetes mellitus subjects during Mg supplementation . No beneficial effect of Mg supplementation was observed on glycemic control , lipids or blood pressure in non-insulin-dependent diabetes mellitus ( NIDDM ) subjects . AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose ( 9.1 + /- 0.5 vs. 10.1 + /- 0.6 mmol/l ; p HbA1c ( 8.5 + /- 0.3 vs. 9.3 + /- 0.3 % ; p AA supplementation on cholesterol ( 5.9 + /- 0.2 vs. 6.2 + /- 0.2 mmol/l ; p triglycerides ( 2.2 + /- 0.2 vs. 2.5 + /- 0.2 ; p AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids" ]	411837cc-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE Studies have suggested that even a single session of physical exercise enhances executive functions . ADHD is among the most common developmental disorders in childhood , but little is known about alternative treatments for this disorder . Therefore , we performed a systematic review of the literature to analyze articles that evaluated the executive functions of children with ADHD after an acute exercise session . METHOD We review ed articles indexed in the PubMed , American Psychiatric Association ( APA ) psychNET , Scopus , and Web of Knowledge data bases between 1980 and 2013 . RESULTS Of 231 articles selected , only three met the inclusion criteria . CONCLUSION Based on these 3 articles , we concluded that 30 min of physical exercise reportedly improved the executive functions of children with ADHD . Due to the small number of articles selected , further studies are needed to confirm these benefits	[ "This study was conducted to determine the effect of acute aerobic exercise on executive function in children with attention deficit hyperactivity disorder ( ADHD ) . Forty children with ADHD were r and omly assigned into exercise or control groups . Participants in the exercise group performed a moderate intensity aerobic exercise for 30 min , whereas the control group watched a running/exercise-related video . Neuropsychological tasks , the Stroop Test and the Wisconsin Card Sorting Test ( WCST ) , were assessed before and after each treatment . The results indicated that acute exercise facilitated performance in the Stroop Test , particularly in the Stroop Color-Word condition . Additionally , children in the exercise group demonstrated improvement in specific WCST performances in Non-perseverative Errors and Categories Completed , whereas no influences were found in those performances in the control group . Tentative explanations for the exercise effect postulate that exercise allocates attention re sources , influences the dorsolateral prefrontal cortex , and is implicated in exercise-induced dopamine release . These findings are promising and additional investigations to explore the efficacy of exercise on executive function in children with ADHD are encouraged", "Objective : Physical activity associates with mental health and neurocognitive function , showing potential for addressing ADHD symptoms . As a preliminary assessment of this potential , the authors piloted a before-school physical activity intervention for young children . Method : Seventeen children ( Grade s K-3 ) exhibiting four or more hyperactivity/impulsivity symptoms on the Disruptive Behavior Disorders Rating Scale ( Pelham , 2002 ) completed about 26 min of continuous moderate-to-vigorous physical activity daily over eight school weeks . The authors administered cognitive , motor , social , and behavioral functioning measures at pre- and postprogram , assessed response inhibition weekly , and coded negative behaviors daily . Results : Several measures showed significant or marginally significant change over time ( effect size = 0.35 - 0.96 ) with additional measures showing meaningful effect size values ( ≥ 0.20 ) . Response inhibition effects were most consistent . Most participants ( 64 % to 71 % ) exhibited overall improvement according to postprogram parent , teacher , and program staff ratings . Conclusion : Physical activity shows promise for addressing ADHD symptoms in young children", "PURPOSE The purpose of this study was to assess the impact of 24 wk of resistance training at two different intensities on cognitive functions in the elderly . METHODS Sixty-two elderly individuals were r and omly assigned to three groups : CONTROL ( N = 23 ) , experimental moderate ( EMODERATE ; N = 19 ) , and experimental high ( EHIGH ; N = 20 ) . The volunteers were assessed on physical , hemodynamic , cognitive , and mood parameters before and after the program . RESULTS On the 1 RM test ( P lean mass ( P = 0.05 ) than the CONTROL group and performed better on the following tests : digit span forward ( P Corsi 's block-tapping task backward ( P = 0.001 ) , similarities ( P = 0.03 ) , Rey-Osterrieth complex figure immediate recall ( P = 0.02 ) , Toulouse-Pieron concentration test errors ( P = 0.01 ) , SF-36 ( general health ) ( P = 0.04 ) , POMS ( tension-anxiety , P = 0.04 ; depression-dejection , P = 0.03 ; and total mood disorder , P = 0.03 ) . The EMODERATE group scored higher means than the CONTROL group on digit span forward ( P Corsi 's block-tapping task backward ( P = 0.01 ) , similarities ( P = 0.02 ) , Rey-Osterrieth complex figure immediate recall ( P = 0.02 ) , SF-36 ( general health , P = 0.005 ; vitality , P = 0.006 ) , POMS ( tension-anxiety , P = 0.001 ; depression-dejection , P = 0.006 ; anger-hostility , P = 0.006 ; fatigue-inertia , P = 0.02 ; confusion-bewilderment , P = 0.02 ; and total mood disorder , P = 0.001 ) . We also found that IGF-1 serum levels were higher in the experimental groups ( EMODERATE , P = 0.02 ; EHIGH , P Moderate- and high-intensity resistance exercise programs had equally beneficial effects on cognitive functioning", "In the present study we use the in vivo microdialysis sampling technique to register extracellular levels of neurotransmitters in the striatum of trained and untrained rats . We further evaluate the influence of 1 h of exercise on the striatal release of dopamine ( DA ) , noradrenaline ( NA ) , glutamate ( GLU ) and gamma-aminobutyric acid ( GABA ) in trained and untrained rats . Male Wistars were r and omly assigned to a training or control group . The exercise training consisted of running on a treadmill for 6 weeks , 5 days week-1 , with running time and speed gradually increased from 30 min at 19 m min-1 during the first week to 80 min at 26 m min-1 during the final training week . The animals of the control group were placed on the treadmill twice a week , and received a total of four ' adaptation sessions ' , in which they exercised 15 - 45 min at 26 m min-1 . Brain dialysates were analysed with microbore liquid chromatography ( LC ) , with electrochemical detection ( monoamines and GABA ) and fluorescence detection ( GLU ) . Soleus citrate synthase and basal striatal concentrations of DA , NA and GLU were significantly different between the trained and control animals . Sixty minutes of exercise significantly increased extracellular DA , NA and GLU levels in both groups , but there was no statistically significant difference in the exercise-induced increase between trained and control animals . There was no statistical difference in basal or exercise-induced GABA levels between trained and control animals . The results indicate that exercise training appears to result in diminished basal activity of striatal neurotransmitters , while maintaining the necessary sensitivity for responses to acute exercise", "Attention deficit hyperactivity disorder ( ADHD ) is related to a deficiency of central catecholamines ( CA ) in cognitive , biochemical , and physical tests , and pharmaceutical intervention may have no effect if it is not accompanied by changes in the environment . The objective of our study was to test the hypothesis that central CA are responsible for the increase in speed reaction seen after physical activity ( PA ) and to measure the impact of high intensity PA on the sustained attention of 25 children diagnosed with ADHD consistent with the Disease Statistical Mental-IV ( DSM-IV ) criteria . It is possible that practicing sports assists in the management of the disorder . The children were divided between users ( US ) and non-users ( NUS ) of methylpheni date ( MTP ) , and the groups were compared to evaluate the effect of the drug on cognition after PA . Post-exercise performance on Conner ’s Continuous Performance Test-II ( CPT ) was not affected by MTP , we observed significant improvements in response time , and we saw normalization in the impulsivity and vigilance measures . These results suggest that the improvements in cognition after physical effort are not CA dependent . Additionally , our results suggest that children ’s attention deficits can be minimized through PA irrespective of treatment with MTP . Additional studies are necessary to confirm that exercise mitigates the harmful symptoms of ADHD" ]	41183844-06ff-11f0-808a-c43d1ab1c353
The usefulness of peak atrial longitudinal strain ( PALS ) in identifying patients at high risk of atrial fibrillation ( AF ) recurrence after radiofrequency ablation ( RFA ) has been investigated in several small AF population s. The aim of this systematic review and meta- analysis was to investigate whether PALS predicts recurrence of AF after RFA treatment . MEDLINE , EMBASE and the Cochrane Library were search ed . Studies investigating the value of PALS in predicting successful RFA in AF patients were selected . Patients underwent echocardiography prior to RFA . Risk of bias was evaluated using the Quality in Prognosis Studies ( QUIPS ) Tool . Twelve studies and a total of 1025 patients suffering from paroxysmal or persistent AF were included . Odds ratios ( OR ) were assessed in a r and om and fixed effects model for univariable and multivariable pooled analyses respectively . PALS was found to be a significant predictor of AF recurrence after RFA across study population s ( Univariable : OR : 1.17 , CI95 % [ 1.03–1.34 ] , p = 0.018 , per 1 % decrease ) ( Multivariable : OR : 1.16 , CI95 % [ 1.09–1.24 ] , p Patients with recurrence had significantly lower PALS prior to RFA than patients who maintained sinus rhythm ( 15.7 ± 5.7 % vs. 23.0 ± 7.0 % , p = 0.016 ) . A pooled analysis of weighted mean differences ( WMD ) also showed a significant difference in PALS between the two groups ( WMD : − 6.57 , CI95 % [ − 8.49 : − 4.65 ] , p Lower values of PALS are associated with an increased risk of AF recurrence after RFA . PALS provides prognostic value in clinical practice	[ "Background The objective of this study was to investigate atrial myocardial properties through two-dimensional ( 2D ) myocardial imaging in patients with atrial fibrillation ( AF ) and its predictive role for recurrence after catheter ablation . Methods and results Echocardiographic examinations were performed in 40 patients with paroxysmal AF before catheter ablation and 40 age- and gender-matched healthy control subjects . Using a software package , bidimensional acquisitions were analyzed to measure longitudinal strain and strain rate for the left atrium ( LA ) . Systolic strain and strain rate in all eight segments , and its average values , were significantly reduced in AF patients compared to controls . During 9 months of follow-up after catheter ablation for AF , 11 of 40 AF patients had AF recurrence . AF recurrence was associated with gender , LA volume index , and average values of systolic strain and strain rate . By multivariate analysis , only average strain was an independent predictor of AF recurrence ( OR = 0.88 , 95 % CI 0.79 - 0.98 , p = 0.018 ) . Conclusions Lower systolic strain of LA was strongly associated with recurrence after catheter ablation . Thus , diverse adjunctive ablation strategies should be considered to reduce recurrence in patients with lower systolic strain", "AIMS The aim of this multicentre study was to determine the normal range and the clinical relevance of the myocardial function of the left atrium ( LA ) analysed by 2D speckle-tracking echocardiography ( 2DSTE ) . METHODS AND RESULTS We analysed 329 healthy adult subjects prospect ively included in 10 centres and a validation group of 377 patients with left ventricular diastolic dysfunction ( LVDD ) . LA myocardial function was analysed by LA strain rate peak during LA contraction ( LA-SRa ) and LA strain peak during LA relaxation ( LA-Strain ) . The range of values of LA myocardial function in healthy subjects was LA-SRa -2.11 ± 0.61 s(-1 ) and LA-Strain 45.5 ± 11.4 % , and the lowest expected values of these LA analyses ( calculated as -1.96 SD from the mean of healthy subjects ) were LA-SRa -0.91 s(-1 ) and LA-Strain 23.1 % . Concerning the clinical relevance of these LA myocardial analyses , LA-SRa and LA-Strain detected subtle LA dysfunction in patients with LVDD , even though LA volumetric measurements were normal . In addition , in these patients we found that the functional class ( dyspnoea-NYHA classification ) was inversely related to both LA-Strain and LA-SRa . CONCLUSION In the present multicentre study analysing a large cohort of healthy subjects and patients with LVDD , the normal range and the clinical relevance of the myocardial function of the LA using 2DSTE have been determined", "OBJECTIVE Since predictors of recurrence of atrial fibrillation ( AF ) after ablation procedures are poorly defined , this prospect i ve study was conducted to assess the value of left atrial ( LA ) deformation imaging with two-dimensional speckle-tracking ( 2D-ST ) to predict AF recurrences after successful ablation procedures . METHODS AND RESULTS One hundred and three consecutive patients ( age 58.1 ± 16.6 years , 72.8 % male ) with AF ( 76 paroxysmal , 27 persistent ) and 30 matched controls underwent transthoracic echocardiography and 2D-ST-LA-deformation analysis with assessment of LA-radial and LA-longitudinal strain ( Sr , Sl ) , and velocities derived from the apical 4- and 2-chamber views ( 4CV , 2CV ) . AF recurrence was assessed during 6 months of follow-up . For determination of AF-related LA changes , AF patients were compared to controls and patients with AF recurrences after ablation procedures ( n = 30 , 29.1 % ) were compared with patients who maintained sinus rhythm ( n = 73 , 70.9 % ) . Atrial deformation capabilities were significantly reduced ( P for AF recurrence after ablation procedures were 2CV-LA-global-strain ( Sr , P = 0.03 ; Sl , P = 0.003 ) , 4CV-LA-gobal-strain ( Sr , P = 0.03 ; Sl , P = 0.02 ) , and regional LA-septal wall-Sl ( P = 0.008 ) . LA-global-strain parameters were superior to regional LA function analysis for the prediction of AF recurrences , with cutoff values ( cov ) , hazard ratios ( HR ) , positive and negative predictive values ( PPV , NPV ) were : 4CVSl cov , 10.79 % ( HR 27.8 , P 2D-ST identifies patients with high risk for AF recurrence after ablation procedures . This imaging technique may help to improve therapeutic guiding for patients with AF", "The incremental value of left atrial ( LA ) deformation analysis by speckle tracking echocardiography compared with LA volume or LA ejection fraction as a cardiovascular risk marker has not been evaluated prospect ively . We sought to compare LA function by speckle tracking echocardiography to other conventional LA parameters for prediction of adverse cardiovascular outcomes . This prospect i ve study included 312 adults ( mean age 71 ± 6 years , 56 % men ) in sinus rhythm who were followed for development of first atrial fibrillation , congestive heart failure , stroke , transient ischemic attack , myocardial infa rct ion , coronary revascularization , and cardiovascular death . Global peak atrial longitudinal strain ( PALS ) by speckle tracking echocardiography was measured in all subjects by averaging all atrial segments . Left atrium was assessed with biplane LA volume , LA ejection fraction , 4-chamber LA area , and M-mode dimension . Of 312 subjects at baseline , 43 had 61 new events during a mean follow-up of 3.1 ± 1.4 years . All LA parameters , traditional parameters , and parameters derived by speckle tracking echocardiography were independently predictive of combined outcomes ( p Overall performance for prediction of cardiovascular events was greatest for global PALS ( area under receiver operator characteristic curve : global PALS 0.83 , indexed LA volume 0.71 , LA ejection fraction 0.69 , LA area 0.64 , LA diameter 0.59 ) . A grade d association between degree of LA enlargement and risk of cardiovascular events was evident only for global PALS and indexed LA volume . In conclusion , global PALS is a strong and independent predictor of cardiovascular events and appears to be superior to conventional parameters of LA analysis", "BACKGROUND Given the potential complications of atrial fibrillation ( AF ) recurrence after ablation , better predictors of the effectiveness of the procedure are necessary to guide patient selection . AIM This prospect i ve study was conducted to evaluate the clinical relevance of global left atrial longitudinal strain ( GLAS ) and AF recurrence after catheter ablation . METHODS In 115 consecutive patients with AF ( persistent , n=62 ; paroxysmal , n=53 ) , transthoracic echocardiography was performed before catheter ablation to assess baseline left atrial mechanical function using speckle tracking echocardiography ( STE ) . RESULTS After 12 months of follow-up , 22 ( 35.5 % ) patients in the persistent AF group and 15 ( 28.3 % ) in the paroxysmal AF group exhibited AF recurrence . In both the paroxysmal and persistent AF population s , patients with recurrence presented with significantly impaired GLAS compared with patients without recurrence . Patients with recurrence also had a significantly higher pro-B-type natriuretic peptide concentration . A receiver operator curve analysis yielded area under the curve values of 0.94 and 0.86 for paroxysmal and persistent AF , respectively . In a multivariable Cox proportional-hazards analysis , GLAS was an independent predictor of AF recurrence after catheter ablation in both the paroxysmal AF group ( hazard ratio : 0.79 , 95 % confidence interval : 0.67 - 0.96 ; P=0.01 ) and the persistent AF group ( hazard ratio : 0.81 , 95 % confidence interval : 0.71 - 0.93 ; P=0.004 ) . CONCLUSIONS In both paroxysmal and persistent AF , decreased baseline left atrial deformation capabilities assessed by two-dimensional STE can help to identify patients at high risk of AF recurrence after catheter ablation . This variable may help to guide c and i date selection and improve therapeutic strategies", "Background Atrial fibrillation ( AF ) is a common arrhythmia with relevant impact on mortality and morbidity . Pulmonary vein isolation ( PVI ) is an established therapy in patients who remain symptomatic under optimal medical therapy . However , up to 70 % of patients present with recurrence of AF after PVI . Therefore , identifying ideal c and i date s is an unmet clinical need . Left atrial ( LA ) fibrosis is associated with reduced LA function . Analysis of LA mechanics using 2D speckle tracking echocardiography ( STE ) might give more insight into LA substrates and be therefore of predictive value . Methods This prospect i ve single-center pilot study included 31 patients ( mean age , 62.3 ± 9.1 years ; 19 males ) with AF who underwent PVI and 20 matched healthy controls ( mean age , 60.6 ± 6.6 years ; 10 males ) . 2D STE strain indices of LA reservoir ( RLA ) , conduit , and , if feasible , contractile function , were analyzed before and 6 months after PVI . Assessment of the LV diastolic function was based on st and ard indices . Responders to PVI were defined as being asymptomatic and free of AF in a 7-day Holter-ECG after 6 months . Results At baseline , all patients with AF had significantly lower reservoir and contractile function compared with controls . After 6 months , 17 patients ( 54.8 % ) were identified as responders . At baseline , the reservoir function was significantly higher in responders compared with nonresponders ( 32.7 ± 11.1 vs. 22.9 ± 10.9 % ; P = 0.019 ) . Only in responders , RLA and contractile LA function improved and reached normal values whereas LA function remained unchanged in nonresponders . In a ROC analysis , a RLA value of ≥19.5 % discriminated responders and nonresponders in patients with persistent AF with a sensitivity of 86 % and a specificity of 100 % ( P = 0.012 ; area under the curve 0.943 ; CI , 0.81–1.0 ) . Conclusions LA reservoir function helps to predict efficacy of PVI after 6 months . Only in responders , reservoir , and contractile function normalized within 6 months after PVI indicating a lower level of atrial remodeling at baseline . No deleterious effects of ablation were detected in nonresponders", "During the past three decades , catheter and surgical ablation of atrial fibrillation ( AF ) have evolved from investigational procedures to their current role as effective treatment options for patients with AF . Surgical ablation of AF , using either st and ard , minimally invasive , or hybrid techniques , is available in most major hospitals throughout the world . Catheter ablation of AF is even more widely available , and is now the most commonly performed catheter ablation procedure . In 2007 , an initial Consensus Statement on Catheter and Surgical AF Ablation was developed as a joint effort of the Heart Rhythm Society ( HRS ) , the European Heart Rhythm Association ( EHRA ) , and the European Cardiac Arrhythmia Society (ECAS).1 The 2007 document was also developed in collaboration with the Society of Thoracic Surgeons ( STS ) and the American College of Cardiology ( ACC ) . This Consensus Statement on Catheter and Surgical AF Ablation was rewritten in 2012 to reflect the many advances in AF ablation that had occurred in the interim.2 The rate of advancement in the tools , techniques , and outcomes of AF ablation continue to increase as enormous research efforts are focused on the mechanisms , outcomes , and treatment of AF . For this reason , the HRS initiated an effort to rewrite and up date this Consensus Statement . Reflecting both the worldwide importance of AF , as well as the worldwide performance of AF ablation , this document is the result of a joint partnership between the HRS , EHRA , ECAS , the Asia Pacific Heart Rhythm Society ( APHRS ) , and the Latin American Society of Cardiac Stimulation and Electrophysiology ( Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia [ SOLAECE ] ) . The purpose of this 2017 Consensus Statement is to provide a state-of-the-art review of the field of catheter and surgical ablation of AF and to report the findings of a writing group , convened by these five international societies . The writing group is charged with defining the indications , techniques , and outcomes of AF ablation procedures . Included within this document are recommendations pertinent to the design of clinical trials in the field of AF ablation and the reporting of outcomes , including definitions relevant to this topic . The writing group is composed of 60 experts representing 11 organizations : HRS , EHRA , ECAS , APHRS , SOLAECE , STS , ACC , American Heart Association ( AHA ) , Canadian Heart Rhythm Society ( CHRS ) , Japanese Heart Rhythm Society ( JHRS ) , and Brazilian Society of Cardiac Arrhythmias ( Sociedade Brasileira de Arritmias Cardiacas [ SOBRAC ] ) . All the members of the writing group , as well as peer review ers of the document , have provided disclosure statements for all relationships that might be perceived as real or potential conflicts of interest . All author and peer review er disclosure information is provided in Appendix A and Appendix B. In writing a consensus document , it is recognized that consensus does not mean that there was complete agreement among all the writing group members . Surveys of the entire writing group were used to identify areas of consensus concerning performance of AF ablation procedures and to develop recommendations concerning the indications for catheter and surgical AF ablation . These recommendations were systematic ally balloted by the 60 writing group members and were approved by a minimum of 80 % of these members . The recommendations were also subject to a 1-month public comment period . Each partnering and collaborating organization then officially review ed , commented on , edited , and endorsed the final document and recommendations . The grading system for indication of class of evidence level was adapted based on that used by the ACC and the AHA.3,4 It is important to state , however , that this document is not a guideline . The indications for catheter and surgical ablation of AF , as well as recommendations for procedure performance , are presented with a Class and Level of Evidence ( LOE ) to be consistent with what the reader is familiar with seeing in guideline statements . A Class I recommendation means that the benefits of the AF ablation procedure markedly exceed the risks , and that AF ablation should be performed ; a Class IIa recommendation means that the benefits of an AF ablation procedure exceed the risks , and that it is reasonable to perform AF ablation ; a Class IIb recommendation means that the benefit of AF ablation is greater or equal to the risks , and that AF ablation may be considered ; and a Class III recommendation means that AF ablation is of no proven benefit and is not recommended . The writing group review ed and ranked evidence supporting current recommendations with the weight of evidence ranked as Level A if the data were derived from high- quality evidence from more than one r and omized clinical trial , meta-analyses of high- quality r and omized clinical trials , or one or more r and omized clinical trials corroborated by high- quality registry studies . The writing group ranked available evidence as Level B-R when there was moderate- quality evidence from one or more r and omized clinical trials , or meta-analyses of moderate- quality r and omized clinical trials . Level B-NR was used to denote moderate- quality evidence from one or more well- design ed , well-executed nonr and omized studies , observational studies , or registry studies . This design ation was also used to denote moderate- quality evidence from meta-analyses of such studies . Evidence was ranked as Level C-LD when the primary source of the recommendation was r and omized or nonr and omized observational or registry studies with limitations of design or execution , meta-analyses of such studies , or physiological or mechanistic studies of human subjects . Level C-EO was defined as expert opinion based on the clinical experience of the writing group . Despite a large number of authors , the participation of several societies and professional organizations , and the attempts of the group to reflect the current knowledge in the field adequately , this document is not intended as a guideline . Rather , the group would like to refer to the current guidelines on AF management for the purpose of guiding overall AF management strategies.5,6 This consensus document is specifically focused on catheter and surgical ablation of AF , and summarizes the opinion of the writing group members based on an extensive literature review as well as their own experience . It is directed to all health care professionals who are involved in the care of patients with AF , particularly those who are caring for patients who are undergoing , or are being considered for , catheter or surgical ablation procedures for AF , and those involved in research in the field of AF ablation . This statement is not intended to recommend or promote catheter or surgical ablation of AF . Rather , the ultimate judgment regarding care of a particular patient must be made by the health care provider and the patient in light of all the circumstances presented by that patient . The main objective of this document is to improve patient care by providing a foundation of knowledge for those involved with catheter ablation of AF . A second major objective is to provide recommendations for design ing clinical trials and reporting outcomes of clinical trials of AF ablation . It is recognized that this field continues to evolve rapidly . As this document was being prepared , further clinical trials of catheter and surgical ablation of AF were under way" ]	411838bc-06ff-11f0-808a-c43d1ab1c353
Background . This paper aim ed to identify condition-specific patient-reported outcome measures used in clinical trials among people with wrist osteoarthritis and summarise empirical peer- review ed evidence supporting their reliability , validity , and responsiveness to change . Methods . A systematic review of r and omised controlled trials among people with wrist osteoarthritis was undertaken . Studies reporting reliability , validity , or responsiveness were identified using a systematic reverse citation trail audit procedure . Psychometric properties of the instruments were examined against predefined criteria and summarised . Results . Thirteen clinical trials met inclusion criteria . The most common patient-reported outcome was the disabilities of the arm , shoulder , and h and question naire ( DASH ) . The DASH , the Michigan H and Outcomes Question naire ( MHQ ) , the Patient Evaluation Measure ( PEM ) , and the Patient-Reported Wrist Evaluation ( PRWE ) had evidence supporting their reliability , validity , and responsiveness . A post-hoc review of excluded studies revealed the AUSCAN Osteoarthritis H and Index as another suitable instrument that had favourable reliability , validity , and responsiveness . Conclusions . The DASH , MHQ , and AUSCAN Osteoarthritis H and Index instruments were supported by the most favourable empirical evidence for validity , reliability , and responsiveness . The PEM and PRWE also had favourable empirical evidence reported for these elements . Further psychometric testing of these instruments among people with wrist osteoarthritis is warranted	[ "Background and purpose The Artelon CMC spacer is design ed for surgical treatment of osteoarthritis ( OA ) in the carpometacarpal joint of the thumb ( CMC-I ) . Good results using this degradable device were previously presented in a pilot study . We now present results from a larger r and omized , controlled , multicenter study . Patients and methods 109 patients ( 94 females ) with a mean age of 60 ( 42–83 ) years , suffering from painful CMC OA , were included in the study at 7 centers in Sweden . The patients were r and omized to Artelon CMC spacer ( test , n = 72 ) or tendon arthroplasty ( control , n = 37 ) at a ratio of 2:1 . Perceived pain was recorded on a visual analog scale ( VAS ) before treatment and after 3 , 6 , and 12 months , when measuring maximal tripod pinch strength ( primary outcome measure ) . In addition , range of motion , radiographic findings , and functional testing were recorded pre- and postoperatively . Results Swelling and pain were more common in the test group and 6 implants were removed because of such symptoms . 5 of these patients did not receive antibiotics preoperatively according to the study protocol . In a per- protocol analysis , i.e. patients without signs of concomitant OA in the scaphoid-trapezium-trapezoid ( STT ) joint and those in the test group who received antibiotics , the mean difference in tripod pinch strength increase , adjusted for baseline , was 1.4 kg in favor of the test group ( not statistically significant ) . Statistically significant pain relief was achieved in both groups , with perceived pain gradually decreasing during the follow-up period . In the intention-to-treat analysis but not in the per- protocol analysis , significantly better pain relief ( VAS ) was obtained in the control group . Patient-perceived disability evaluated by the DASH question naire improved in both groups . Interpretation The Artelon CMC spacer did not show superior results compared to tendon interposition arthroplasty . Proper use of preoperative antibiotics and a thorough patient selection appear to be important for the results", "OBJECTIVE : To compare the functional results of carpectomy and four‐corner fusion surgical procedures for treating osteoarthrosis following carpal trauma . METHODS : In this prospect i ve r and omized study , 20 patients underwent proximal row carpectomy or four‐corner fusion to treat wrist arthritis and their functional results were compared . The midcarpal joint was free of lesions in all patients . RESULTS : Both proximal row carpectomy and four‐corner fusion reduced the pain . All patients had a decreased range of motion after surgery . The differences between groups were not statistically significant . CONCLUSIONS : Functional results of the two procedures were similar as both reduced pain in patients with scapholunate advanced collapse/scaphoid non‐union advanced collapse ( SLAC/SNAC ) wrist without degenerative changes in the midcarpal joint", "This prospect i ve study compared the outcome --subjective , objective and radiographic -- of two surgical techniques for treating basal joint arthritis of the thumb : a \" simple \" trapeziectomy ( group I ) and a ligament reconstruction/tendon ( group II ) interposition technique . There were respectively 22 patients in group I and 34 in group II , all women with primary osteoarthritis . Both techniques gave favourable results and there were no significant differences for pain relief , patient satisfaction , mobility , DASH-score , key pinch force and gripping force . However in group II , the trapezial height was better preserved indicating that the proximal migration of the thumb was prevented or limited . There was also a significant correlation between the remaining trapezial space and key pinch force", "Background Assessment s of change in subjective patient reported outcomes such as health-related quality of life ( HRQoL ) are a key component of many clinical and research evaluations . However , conventional longitudinal evaluation of change may not agree with patient perceived change if patients ' underst and ing of the subjective construct under evaluation changes over time ( response shift ) or if patients ' have inaccurate re collection ( recall bias ) . This study examined whether older adults ' perception of change is in agreement with conventional longitudinal evaluation of change in their HRQoL over the duration of their hospital stay . It also investigated this level of agreement after adjusting patient perceived change for recall bias that patients may have experienced . Methods A prospect i ve longitudinal cohort design nested within a larger r and omised controlled trial was implemented . 103 hospitalised older adults participated in this investigation at a tertiary hospital facility . The EQ-5D utility and Visual Analogue Scale ( VAS ) scores were used to evaluate HRQoL. Participants completed EQ-5D reports as soon as they were medically stable ( within three days of admission ) then again immediately prior to discharge . Three methods of change score calculation were used ( conventional change , patient perceived change and patient perceived change adjusted for recall bias ) . Agreement was primarily investigated using intraclass correlation coefficients ( ICC ) and limits of agreement . Results Overall 101 ( 98 % ) participants completed both admission and discharge assessment s. The mean ( SD ) age was 73.3 ( 11.2 ) . The median ( IQR ) length of stay was 38 ( 20 - 60 ) days . For agreement between conventional longitudinal change and patient perceived change : ICCs were 0.34 and 0.40 for EQ-5D utility and VAS respectively . For agreement between conventional longitudinal change and patient perceived change adjusted for recall bias : ICCs were 0.98 and 0.90 respectively . Discrepancy between conventional longitudinal change and patient perceived change was considered clinical ly meaningful for 84 ( 83.2 % ) of participants , after adjusting for recall bias this reduced to 8 ( 7.9 % ) . Conclusions Agreement between conventional change and patient perceived change was not strong . A large proportion of this disagreement could be attributed to recall bias . To overcome the invalidating effect of response shift ( on conventional change ) and recall bias ( on patient perceived change ) a method of adjusting patient perceived change for recall bias has been described", "We r and omly selected 39 patients undergoing excision of the trapezium for osteoarthritis of the first carpometacarpal joint into two groups , with mobilisation either at one or at four weeks after operation . The patients were review ed at a median of six months ( 6 to 8) . The clinical details , the severity of the disease and the preoperative clinical measurements of both groups were similar . Excision of the trapezium result ed in significant improvement in objective and subjective function . Comparison of the outcomes of the two groups showed no differences except that patients found early mobilisation significantly more convenient . Although there was no significant difference in the range of movement between the groups , there was a small loss of movement at the metacarpophalangeal joint in the late mobilisation group . Our findings show that simple excision of the trapezium is an effective procedure for patients with carpometacarpal osteoarthritis of the thumb and that prolonged splintage is neither necessary nor desirable", "Background Clinical practice and clinical research has made a concerted effort to move beyond the use of clinical indicators alone and embrace patient focused care through the use of patient reported outcomes such as health-related quality of life . However , unless patients give consistent consideration to the health states that give meaning to measurement scales used to evaluate these constructs , longitudinal comparison of these measures may be invalid . This study aim ed to investigate whether patients give consideration to a st and ard health state rating scale ( EQ-VAS ) and whether consideration of good and poor health state descriptors immediately changes their self-report . Methods A r and omised crossover trial was implemented amongst hospitalised older adults ( n = 151 ) . Patients were asked to consider descriptions of extremely good ( Description-A ) and poor ( Description-B ) health states . The EQ-VAS was administered as a self-report at baseline , after the first descriptors ( A or B ) , then again after the remaining descriptors ( B or A respectively ) . At baseline patients were also asked if they had considered either EQ-VAS anchors . Results Overall 106/151 ( 70 % ) participants changed their self-evaluation by ≥5 points on the 100 point VAS , with a mean ( SD ) change of + 4.5 ( 12 ) points ( p the best health VAS anchor , of the 77 who did 59 ( 77 % ) thought the good health descriptors were more extreme ( better ) then they had previously considered . Similarly 85/151 ( 66 % ) participants did not consider the worst health anchor of the 66 who did 63 ( 95 % ) thought the poor health descriptors were more extreme ( worse ) then they had previously considered . Conclusions Health state self-reports may not be well considered . An immediate significant shift in response can be elicited by exposure to a mere description of an extreme health state despite no actual change in underlying health state occurring . Caution should be exercised in research and clinical setting s when interpreting subjective patient reported outcomes that are dependent on brief anchors for meaning . Trial Registration Australian and New Zeal and Clinical Trials Registry ( # ACTRN12607000606482 )", "Background Expectations held by patients and health professionals may affect treatment choices and participation ( by both patients and health professionals ) in therapeutic interventions in contemporary patient-centered healthcare environments . If patients in rehabilitation setting s overestimate their discharge health-related quality of life , they may become despondent as their progress falls short of their expectations . On the other h and , underestimating their discharge health-related quality of life may lead to a lack of motivation to participate in therapies if they do not perceive likely benefit . There is a scarcity of empirical evidence evaluating whether patients ’ expectations of future health states are accurate . The purpose of this study is to evaluate the accuracy with which older patients admitted for subacute in-hospital rehabilitation can anticipate their discharge health-related quality of life . Methods A prospect i ve longitudinal cohort investigation of agreement between patients ’ anticipated discharge health-related quality of life ( as reported on the EQ-5D instrument at admission to a rehabilitation unit ) and their actual self-reported health-related quality of life at the time of discharge from this unit was undertaken . The mini-mental state examination was used as an indicator of patients ’ cognitive ability . Results Overall , 232(85 % ) patients had all assessment data completed and were included in analysis . Kappa scores ranged from 0.42 - 0.68 across the five EQ-5D domains and two patient cognition groups . The percentage of exact correct matches within each domain ranged from 69 % to 85 % across domains and cognition groups . Overall 40 % of participants in each cognition group correctly anticipated all of their self-reported discharge EQ-5D domain responses . Conclusions Patients admitted for subacute in-hospital rehabilitation were able to anticipate their discharge health-related quality of life on the EQ-5D instrument with a moderate level of accuracy . This finding adds to the foundational empirical work supporting joint treatment decision making and patient-centered models of care during rehabilitation following acute illness or injury . Accurate patient expectations of the impact of treatment ( or disease progression ) on future health-related related quality of life is likely to allow patients and health professionals to successfully target interventions to priority areas where meaningful gains can be achieved", "Objective : To evaluate the responsiveness of patient reported outcomes ( PROs ) , including fatigue , sleep , activity limitation , and quality of life , in patients with rheumatoid arthritis ( RA ) . Methods : Data were considered from a r and omised controlled trial comparing abatacept ( n = 258 ) with placebo ( n = 133 ) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy ( ATTAIN study ) . PROs assessed included SF-36 , activity limitation , fatigue , and sleep . For each outcome the treatment difference , relative per cent improvement , st and ardised response mean ( SRM ) , and relative efficiency for assessing an outcome ’s ability to detect a treatment effect relative to tender joint count ( TJC ) were calculated . A relative efficiency > 1 suggests a measure that is more efficient than TJC in detecting treatment effect . Results : Moderate to large SRMs ( ⩾0.6 ) were observed for the PRO measures . In particular , SRMs ( 95 % confidence interval ) were : physician global , 0.72 ( 0.51 to 0.94 ) ; HAQ , 0.63 ( 0.42 to 0.85 ) ; SF-36 physical component score , 0.62 ( 0.40 to 0.83 ) ; SF-36 bodily pain , 0.68 ( 0.46 to 0.90 ) ; and fatigue , 0.59 ( 0.38 to 0.81 ) . Relative efficiencies for physician global ( 1.6 ) , SF-36 bodily pain domain ( 1.4 ) , pain intensity ( 1.4 ) , HAQ ( 1.2 ) , SF-36 physical component score ( 1.2 ) , fatigue ( 1.1 ) , and patient global assessment ( 1.04 ) were all more responsive than TJC . The SF-36 mental component score ( 0.3 ) , swollen joint count ( 0.6 ) , activity limitation ( 0.8 ) , sleep ( 0.7 ) , and C reactive protein ( 0.9 ) were less responsive . Conclusions : Using PROs for evaluating treatments for RA can detect improvements and will identify changes that are important to patients . In general , physical assessment s are more responsive to an effective treatment than mental assessment", " Forty-three h and s in 41 adults with osteoarthrosis of the trapeziometacarpal joint were allocated r and omly to undergo a trapeziectomy through either an anterior approach or the posterior ( dorsoradial ) approach . Forty h and s were available for review at a median of 33 months postoperatively . The demographic characteristics , severity of disease and pre-operative measurements of the two groups were indistinguishable . Trapeziectomy result ed in significantly improved objective and subjective function in both groups , but the anterior approach group had better outcomes for power , scar tenderness and satisfaction . Scar-related complications were three times more common in the posterior group . Trapeziectomy is a good method of treating osteoarthritis of the thumb base , but outcomes for the anterior approach are equally good or better than with the posterior", "OBJECTIVE Prospect i ve assessment of the efficacy and tolerability of intra-articular sodium hyaluronate ( SH ; Ostenil mini ) and triamcinolone acetonide ( TA ; Volon A10 ) for treatment of osteoarthritis ( OA ) of the carpometacarpal ( CMC ) joint of the thumb in a 26-week , controlled , r and omized , on an intention to treat , masked-observer study . METHODS Patients were treated with three intra-articular injections of either SH ( n = 28 ) or TA ( n = 28 ) . Primary assessment s were pain according to a 100 mm visual analogue scale and extensive clinical and functional parameters such as swelling , grip power and range of motion . The population was analysed using one- and two-sided Mann-Whitney ( MW ) estimators . RESULTS Maximum pain relief occurred at 2 - 3 weeks for TA and at week 26 for SH after the first intra-articular injection . At weeks 2 - 3 TA was significantly better than SH ( MW : 0.3319 and 0.3063 ; P = 0.9827 and 0.9929 ) . At week 26 a slight superiority of SH could be observed ( MW : 0.53 ; P = 0.3624 ) and non-inferiority could be proven . After 26 weeks lateral pinch power was significantly better in the SH-group ( MW : 0.6331 ; P = 0.0226 ) . In all , 88.0 % of patients treated with SH and 79.1 % of the TA-group described pain improvement after 26 weeks . Both agents were well tolerated . No adverse events with causal connection to the investigational products occurred . CONCLUSION A single course of three SH injections is effective in relieving pain and improving joint function in patients with OA of the CMC joint of the thumb . Although in comparison with triamcinolone its effects are achieved more slowly , the results indicate a superior long-lasting effect of hyaluronan at 6 months after end of treatment period", "An important method ological issue in measuring health-related quality of life is whether instruments such as SF-36 and EQ can be used on an elderly population . This paper aims to test the completion , reliability and validity of the SF-36 and Euroqol on an elderly female population , and to compare them with the OPCS Disability Survey . Three hundred and eighty women aged 75 and over participated in a r and omized controlled trial of the use of clodronate provided the sample . As part of the trial , patients were asked to complete the UK SF-36 and Euroqol , and the OPCS disability survey instrument administered by interview in a hospital clinic at baseline . A r and om sub sample of respondents were retested six months later . The SF-36 achieved poorer levels of completion by dimension ( 68.1%–88.9 % ) than the OPCS ( 99.2 % ) and Euroqol ( 84%–93.5 % ) instruments . There were no major floor effects in the distribution of scores , except for the role dimensions of SF-36 . Correlation between test-retest were significant for all instruments , but lower for the role dimensions and social functioning of SF-36 , and these dimensions also had 95 % Cls for the mean differences in excess of 10 points . There was substantial agreement between the three instruments , and evidence for their construct validity against age and recent use of health services . The sensitivities of the instruments were tested through hypothetical changes in health status . There was some evidence of greater sensitivity to lower levels of morbidity in the SF-36 . Where brevity is required and the health changes are expected to be substantial , then EQ may be sufficient . For greater sensitivity SF-36 seems to have an advantage , however lower completion rates and problems with consistency suggest it requires adaptation . One solution would be to use interviewer administration . Another would be to change the SF-36 to make it more suitable for use in elderly people , although this may reduce its usefulness as a generic instrument", "OBJECTIVE To evaluate the efficacy of continuous low-level heat wrap therapy for the treatment of various sources of wrist pain including strain and sprain ( SS ) , tendinosis ( T ) , osteoarthritis ( OA ) , and carpal tunnel syndrome ( CTS ) . DESIGN Prospect i ve , r and omized , parallel , single-blind ( investigator ) , placebo-controlled , multicenter clinical trial . SETTING Two community-based research facilities . PARTICIPANTS Ninety-three patients ( age range , 18 - 65 y ) with wrist pain . INTERVENTION Subjects with moderate or greater wrist pain were r and omized and stratified to 1 of the following treatments : efficacy evaluation ( heat wrap , n=39 ; oral placebo , n=42 ) or blinding ( oral acetaminophen , n=6 ; unheated wrap , n=6 ) . Data were recorded over 3 days of treatment and 2 days of follow-up . MAIN OUTCOME MEASURES The primary comparison was between the heat wrap and the oral placebo group among SS/T/OA subjects for pain relief . Outcome measures included pain relief ( 0 - 5 scale ) , joint stiffness ( 101-point numeric rating scale ) , grip strength measured by dynamometry , and perceived pain and disability ( Patient Rated Wrist Evaluation [ PRWE ] ) ; subjects with CTS also completed the Symptom Severity Scale and Functional Status Scale . RESULTS Heat wrap therapy showed significant benefits in day 1 to 3 mean pain relief ( P=.045 ) and increased day 3 grip strength ( P=.02 ) versus oral placebo for the SS/T/OA group . However , joint stiffness and PRWE results were comparable between the 2 treatments . For the CTS group , heat wraps provided greater day 1 to 3/hour 0 to 8 mean pain relief ( P=.001 ) , day 1 to 3 mean joint stiffness reduction ( P=.004 ) , increased day 3 grip strength ( P=.003 ) , reduced PRWE scores ( P=.0015 ) , reduced symptom severity ( P=.001 ) , and improved functional status ( P=.04 ) . In addition , the heat wrap showed significant extended benefits through follow-up ( day 5 ) in the CTS group . CONCLUSIONS Continuous low-level heat wrap therapy was efficacious for the treatment of common conditions causing wrist pain and impairment", " Forty-three patients were r and omly allocated to undergo either trapeziectomy alone ( control ) or with a ligament reconstruction and tendon interposition ( LRTI ) using an abductor pollicis longus tendon slip . The patients were review ed at a median 13 ( range , 7–29 ) months after surgery . The demographic characteristics , severity of disease and pre-operative clinical measurements of the two study groups were indistinguishable but LRTI lengthened the operation by approximately 15 minutes . Both groups expressed equal satisfaction with the operation and there were no significant differences between the two treatment groups . Simple trapeziectomy is an effective operation for osteoarthrosis at the base of the thumb and the addition of a ligament reconstruction was not shown to confer any additional benefit", "The purpose of this study was to compare the objective , subjective , and radiographic responses of patients with carpometacarpal joint osteoarthritis ( CMCJ-OA ) wearing a prefabricated neoprene splint ( PFN ) , which crosses the CMCJ and metacarpophalangeal joint , with those of patients wearing a custom-made thermoplastic short opponens splint ( CMT ) , which crosses only the CMCJ . Patients ( N = 25 ) with first CMCJ stage I and II osteoarthritis were assigned r and omly to wear either the PFN splint or the CMT splint for one week . After one week , the subjects rated their function in the splint and their satisfaction and pain levels on visual analogue scales . Pinch measurements were performed and x-rays were taken to assess carpometacarpal subluxation . The second splint was then applied for one week and all measures were repeated . The subjects rated the PFN splint significantly higher , and most reported that they would choose the PFN splint over the CMT splint for daily and long-term use . Both pain and function were improved with splinting , but the effect was amplified with the PFN splint compared with the CMT splint . Both splints reduced subluxation at the first carpometacarpal joint , but the CMT effect was greater . This study further supports current evidence that subjects with stage I and II first CMCJ-OA will have pain relief with thumb splinting . In addition , the PFN splint will provide greater relief when compared with the CMT splint . Furthermore , this study reveals that patients prefer the PFN splint to the CMT splint", "The quality of life ( QOL ) of the Chinese ‘ floating ’ migrant population is of growing concern . Urban construction workers are the main migrant population in China , but there is little published research on their QOL . The reliability and validity of the 36-Item Short Form Health Survey ( SF-36 ) question naire were assessed by conducting a population -based study of migrant construction workers in Shenyang , China . Two construction sites were r and omly selected from each of the five districts of Shenyang City and 1200 copies of the question naire were distributed to rurally-registered , non-Shenyang workers aged ≥ 16 years at these sites . A total of 1125 question naires were evaluated . The overall Cronbach 's a coefficient of the SF-36 question naire was 0.821 while the respective Cronbach 's α coefficient for each dimension was > 0.70 . Results showed that the SF-36 question naire demonstrated good reliability and validity , and that it can be used to measure QOL among Chinese migrant urban construction workers" ]	41183934-06ff-11f0-808a-c43d1ab1c353
CONTEXT And rogen-deficient men are at increased risk of osteoporosis . The extent to which testosterone can prevent and treat osteoporosis in men remains unclear . OBJECTIVE AND DESIGN We performed a systematic review and meta- analysis of r and omized placebo-controlled trials in men to estimate the effect of testosterone use on bone health outcomes . DATA SOURCES The review encompassed librarian- design ed search strategies using MEDLINE ( 1966 to March 2005 ) , EMBASE ( 1988 to March 2005 ) , and Cochrane CENTRAL ( inception to March 2005 ) ; a review of reference lists from included studies ; and content expert files . DATA COLLECTION Independently and in duplicate , we assessed the method ological quality of the eligible trials and collected data on bone mineral density and bone fractures at the longest point of complete follow-up . DATA SYNTHESIS We included eight trials enrolling 365 patients . Two trials followed patients for more than 1 yr . Meta- analysis of these trials showed that , compared with placebo , i m testosterone was associated with an 8 % ( 95 % confidence interval , 4 % , 13 % ) gain in lumbar bone mineral density and transdermal testosterone had no significant impact . Testosterone use was associated with a nonsignificant 4 % ( 95 % confidence interval , -2 % , 9 % ) gain in femoral neck bone mineral density with unexplained differences in results across trials ( 26 % of these differences were not explained by chance alone ) . No trials measured or reported the effect of testosterone on fractures . CONCLUSIONS Intramuscular testosterone moderately increased lumbar bone density in men ; the results on femoral neck bone density are inconclusive . Without bone fracture data , the available trials offer weak and indirect inferences about the clinical efficacy of testosterone on osteoporosis prevention and treatment in men	[ "Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy", "Older men , particularly those with low serum testosterone ( T ) levels , might benefit from T therapy to improve bone mineral density ( BMD ) and reduce fracture risk . Concerns exist , however , about the impact of T therapy on the prostate in older men . We hypothesized that the combination of T and finasteride ( F ) , a 5 alpha-reductase inhibitor , might increase BMD in older men without adverse effects on the prostate . Seventy men aged 65 yr or older , with a serum T less than 12.1 nmol/liter on two occasions , were r and omly assigned to receive one of three regimens for 36 months : T enanthate , 200 mg i m every 2 wk with placebo pills daily ( T-only ) ; T enanthate , 200 mg every 2 wk with 5 mg F daily ( T+F ) ; or placebo injections and pills ( placebo ) . Low BMD was not an inclusion criterion . We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry . Prostate-specific antigen ( PSA ) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate . Fifty men completed the 36-month protocol . By an intent-to-treat analysis including all men for as long as they contributed data , T therapy for 36 months increased BMD in these men at the lumbar spine [ 10.2 + /- 1.4 % ( mean percentage increase from baseline + /- SEM ; T-only ) and 9.3 + /- 1.4 % ( T+F ) vs. 1.3 + /- 1.4 % for placebo ( P hip [ 2.7 + /- 0.7 % ( T-only ) and 2.2 + /- 0.7 % ( T+F ) vs. -0.2 + /- 0.7 % for placebo , ( P increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip . After 6 months of therapy , urinary deoxypyridinoline ( a bone-resorption marker ) decreased significantly compared with baseline in both the T-only and T+F groups ( P PSA increased significantly from baseline in the T-only group ( P Prostate volume increased in all groups during the 36-month treatment period , but this increase was significantly less in the T+F group compared with both the T-only and placebo groups ( P = 0.02 ) . These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months , both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men . In addition , the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy . These findings have important implication s for the prevention and treatment of osteoporosis in older men with low T levels", "BACKGROUND Despite its association with disability , death , and increased medical costs , osteoporosis in men has been relatively neglected as a subject of study . There have been no large , controlled trials of treatment in men . METHODS In a two-year double-blind trial , we studied the effect of 10 mg of alendronate or placebo , given daily , on bone mineral density in 241 men ( age , 31 to 87 years ; mean , 63 ) with osteoporosis . Approximately one third had low serum free testosterone concentrations at base line ; the rest had normal concentrations . Men with other secondary causes of osteoporosis were excluded . All the men received calcium and vitamin D supplements . The main outcome measures were the percent changes in lumbar-spine , hip , and total-body bone mineral density . RESULTS The men who received alendronate had a mean ( + /-SE ) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine , 2.5+/-0.4 percent at the femoral neck , and 2.0+/-0.2 percent for the total body ( P placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent ( P femoral-neck or total-body bone mineral density . The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites ( P incidence of vertebral fractures was lower in the alendronate group than in the placebo group ( 0.8 percent vs. 7.1 percent , P=0.02 ) . Men in the placebo group had a 2.4-mm decrease in height , as compared with a decrease of 0.6 mm in the alendronate group ( P=0.02 ) . Alendronate was generally well tolerated . CONCLUSIONS In men with osteoporosis , alendronate significantly increases spine , hip , and total-body bone mineral density and helps prevent vertebral fractures and decreases in height", "BACKGROUND A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men . The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - -87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone ( two 2.5-mg patches per day ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex-hormone binding globulin [ SHBG ] , estradiol , and estrone ) , bone mineral density ( BMD ; femoral neck , Ward 's triangle , trochanter , lumbar spine , and total body ) , bone turnover markers , lower extremity muscle strength , percent body fat , lean body mass , hemoglobin , hematocrit , prostate symptoms , and prostate specific antigen ( PSA ) levels . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . In these men , bioavailable testosterone levels increased from 3.2 + /- 1.2 nmol/l ( SD ) to 5.6 + /- 3.5 nmol/l ( p estradiol levels in either group , estrone levels increased in the testosterone group ( 103 + /- 26 pmol/l to 117 + /- 33 pmol/l ; p femoral neck BMD , whereas the control group lost 1.6 % over 12 months ( p = .015 ) . No significant changes were seen in markers of bone turnover in either group . Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores . Strength increased 38 % ( p = .017 ) in the testosterone group and 27 % in the control group ( p = .06 ) , with no statistical difference between the groups . In the testosterone group , body fat decreased from 26.3 + /- 5.8 % to 24.6 + /- 6.5 % ( p = .001 ) , and lean body mass increased from 56.2 + /- 5.3 kg to 57.2 + /- 5.1 kg ( p = .001 ) , whereas body mass did not change . Men receiving testosterone had an increase in PSA from 2.0 + /- 1.4 microg/l to 2.6 + /- 1.8 microg/l ( p = .04 ) , whereas men receiving placebo had an increase in PSA from 1.9 + /- 1.0 microg/l to 2.2 + /- 1.5 microg/l ( p = .09 ) . No significant differences between groups were seen in hemoglobin , hematocrit , symptoms or signs of benign prostate hyperplasia , or PSA levels . CONCLUSIONS Transdermal testosterone ( 5 mg/d ) prevented bone loss at the femoral neck , decreased body fat , and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels . In addition , both testosterone and placebo groups demonstrated gains in lower extremity muscle strength , possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but result ed in no change in signs or symptoms of prostate hyperplasia", "Long-term glucocorticoid therapy in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone . We tested the effect of two and rogens , testosterone and its minimally aromatizable analog n and rolone , on muscle mass ( dual x-ray absorptiometry ) , muscle strength ( knee flexion and extension by isokinetic dynamometry ) , bone mineral density ( BMD ) , and quality of life ( Qualeffo-41 question naire ) in 51 men on a mean daily prednisone dose of 12.6 + /- 2.2 mg . Men were r and omized , double blind , to testosterone ( 200 mg mixed esters ) , n and rolone decanoate ( 200 mg ) , or placebo given every fortnight by i m injection for 12 months . At 12 months , both and rogens increased muscle mass ( mean change from baseline + 3.5 % , + 5.8 % , and -0.9 % in testosterone , n and rolone , and placebo groups , respectively , P muscle strength ( P Lumbar spine BMD increased significantly only in men treated with testosterone ( 4.7 + /- 1.1 % , P hip or total body BMD . Testosterone , but not n and rolone or placebo , improved overall quality of life ( P and rogen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for and rogen action on bone but not on muscle", "The pharmacokinetics , efficacy , and safety of the And roderm testosterone ( T ) transdermal system ( TTD ) and intramuscular T enanthate injections ( i.m . ) for the treatment of male hypogonadism were compared in a 24-week multicenter , r and omized , parallel-group study . Sixty-six adult hypogonadal men ( 22 - 65 years of age ) were withdrawn from prior i.m . treatment for 4 - 6 weeks and then r and omly assigned to treatment with TTD ( two 2.5-mg systems applied nightly ) or i.m . ( 200 mg injected every 2 weeks ) ; there were 33 patients per group . Twenty-six patients in the TTD group and 32 in the i.m . group completed the study . TTD treatment produced circadian variations in the levels of total T , bioavailable T , dihydrotestosterone , and estradiol within the normal physiological ranges . i.m . treatment produced supraphysiological levels of T , bioavailable T , and estradiol ( but not dihydrotestosterone ) for several days after each injection . Mean morning sex hormone levels were within the normal range in greater proportions of TTD patients ( range , 77 - 100 % ) than i.m . patients ( range , 19 - 84 % ) . Both treatments normalized LH levels in approximately 50 % of patients with primary hypogonadism ; however , LH levels were suppressed to the subnormal range in 31 % of i.m . patients vs. 0 % of TTD patients . Both treatments maintained sexual function ( assessed by question naire and Rigiscan ) and mood ( Beck Depression Inventory ) at the prior treatment levels . Prostate-specific antigen levels , prostate volumes , and lipid and serum chemistry parameters were comparable in both treatment groups . Transient skin irritation from the patches was reported by 60 % of the TTD patients , but caused only three patients ( 9 % ) to discontinue treatment . i.m . treatment produced local reactions in 33 % of patients and was associated with significantly more abnormal hematocrit elevations ( 43.8 % of patients ) compared with TTD treatment ( 15.4 % of patients ) . Gynecomastia resolved more frequently during TTD treatment ( 4 of 10 patients ) than with i.m . treatment ( 1 of 9 patients ) . Although both treatments seem to be efficacious for replacing T in hypogonadal men , the more physiological sex hormone levels and profiles associated with TTD may offer possible advantages over i.m . in minimizing excessive stimulation of erythropoiesis , preventing/ameliorating gynecomastia , and not over-suppressing gonadotropins", "The objective of this study was to determine whether decreased gonadal function is a risk factor for hip fracture in elderly men . The study was a matched case-control study performed at an in-hospital orthopedic service at a semi-rural and academic tertiary care center . The patients were seventeen men who presented with hip fractures after simple falls over a 10-month period , 11 men with a history of hip fractures in the preceding 25 months , and 28 r and omly selected age- , race- , and living status-matched control subjects ( mean age 73 years ) . Serum pooled total testosterone ( 9.2 ± 5.5 nmol/ L vs. 12.8 ± 5.4 nmol/L ; p and free testosterone ( 37.9 ± 18.8 pmol/L vs. 48.4 ± 20.6 pmol/L ; p . Testosterone deficiency was found in 20 ( 71 % ) hip fracture men vs. 9 ( 32 % ) of the controls ( p = 0.003 ; odds ratio 5.3 ) . Analysis of testosterone values within the stratum of absence of any chronic disorder revealed similar results . Serum 25-hydroxyvitamin D levels were significantly lower in the hip fracture group than in control men ( p that gonadal deficiency appears to be an important and heretofore understudied risk factor for hip fractures in men . Prevention of hip fractures in men may involve early recognition and treatment of testosterone", "As men age , their serum testosterone concentrations decrease , as do their bone densities . Because bone density is also low in hypogonadal men , we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months . We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment . Ninety-six men completed the entire 36-month protocol . The mean serum testosterone concentration in the men treated with testosterone increased from 367 + /- 79 ng/dL ( + /-SD ; 12.7 + /- 2.7 nmol/L ) before treatment to 625 + /- 249 ng/dL ( 21.7 + /- 8.6 nmol/L ; P mean bone mineral density of the lumbar spine increased ( P placebo-treated ( 2.5 + /- 0.6 % ) and testosterone-treated ( 4.2 + /- 0.8 % ) groups , but the mean changes did not differ between the groups . Linear regression analysis , however , demonstrated that the lower the pretreatment serum testosterone concentration , the greater the effect of testosterone treatment on lumbar spine bone density from 0 - 36 months ( P = 0.02 ) . This analysis showed a minimal effect ( 0.9 + /- 1.0 % ) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL ( 13.9 nmol/L ) , but an increase of 5.9 + /- 2.2 % for a pretreatment testosterone concentration of 200 ng/dL ( 6.9 nmol/L ) . Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall , but did increase it in those men with low pretreatment serum testosterone concentrations", "Thirty-five male patients , aged 34 - 79 yr , with definite rheumatoid arthritis ( RA ) were recruited from out-patient clinics and r and omized to receive monthly injections of testosterone enanthate 250 mg or placebo as an adjunct therapy for 9 months . Endpoints included disease activity parameters and bone mineral density ( BMD ) . At baseline , there were negative correlations between the ESR and serum testosterone ( r = -0.42 , P BMD ( hip , r = -0.65 , P vertebral fracture , most having multiple fractures . Back pain , however , was not more prevalent in fracture patients ( 55 % vs 50 % ) . Disease activity was significantly higher in the fracture group ( joint score P Thirty patients completed the trial , 15 receiving testosterone and 15 receiving placebo . There were significant rises in serum testosterone , dihydrotestosterone and oestradiol in the treatment group . There was no significant effect of treatment on disease activity overall , five patients receiving testosterone underwent a \" flare ' . Differences in mean BMD following testosterone or placebo were non-significant ( spine : + 1.2 % vs -1.1 % ; femur : -0.3 % vs + 0.3 % ) . There was no suggestion of a positive effect of testosterone on disease activity in men with RA", "Multiple endocrine and metabolic consequences of human immunodeficiency virus ( HIV ) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome ( AIDS ) wasting syndrome . Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting . Prior studies have not examined the effects of anabolic agents on bone mineral density ( BMD ) or bone turnover in these men . To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting , we r and omly assigned 54 eugonadal men with AIDS wasting ( weight 10 % from preillness baseline ) to receive either testosterone enanthate ( 200 mg/week , i m ) or placebo and to progressive resistance training ( 3 times/week ) or no training in a 2 x 2 factorial study design for 3 months . The BMD of the lumbar spine , proximal femur , and total body ; lean body mass ; and fat mass were measured by dual energy x-ray absorptiometry . Total body scans were repeated after 12 weeks of therapy . Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects . Compared with controls , lumbar spine BMD ( 1.021 + /- 0.018 vs. 1.084 + /- 0.025 g/cm(2 ) ; P = 0.04 ) and total hip BMD ( 0.951 + /- 0.017 vs. 1.070 + /- 0.019 g/cm(2 ) ; P T-scores were lower in men with AIDS wasting at the lumbar spine ( -0.62 + /- 0.17 vs. -0.07 + /- 0.23 , P = 0.05 ) and total hip ( -0.65 + /- 0.11 vs. + 0.20 + /- 0.014 , P Total hip T scores were less than -1.0 in 33 % of men with AIDS wasting . Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD . Serum osteocalcin levels were lower ( 3.63 + /- 0.29 vs. 4.54 + /- 0.31 nmol/L ; P urinary N-telopeptide excretion was higher ( 45.4 + /- 4.5 vs. 26.8 + /- 3.0 nmol BCE/mmol creatinine ; P = 0.004 ) in men with AIDS wasting than in controls . Lumbar spine BMD , as assessed on regional total body dual energy x-ray absorptiometry scan , increased over the 12-week treatment period in response to testosterone ( + 2.4 + /- 1.3 vs. -1.3 + /- 1.0 % , testosterone vs. placebo , respectively ; P = 0.02 ) , but not in response to training ( + 0.8 + /- 1.0 vs. + 0.4 + /- 1.3 % , training vs. no training ; P = 0.70 ) . Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting . Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men . Testosterone administration , but not resistance training , over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting", "A decline in testicular function is recognized as a common occurrence in older men . However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines . This study was undertaken to examine the year-long effects of testosterone administration in this patient population . Fifteen hypogonadal men ( mean age 68 + /- 6 yr ) were r and omly assigned to receive a placebo , and 17 hypogonadal men ( mean age 65 + /- 7 yr ) were r and omly assigned to receive testosterone . Hypogonadism was defined as a bioavailable testosterone placebo or 200 mg testosterone cypionate biweekly for 12 months . The main outcomes measured included grip strength , hemoglobin , prostate-specific antigen , leptin , and memory . Testosterone improved bilateral grip strength ( P hemoglobin ( P testosterone had greater decreases in leptin than those assigned to the control group ( mean + /- SEM : -2.0 + /- 0.9 ng/dL vs. 0.8 + /- 0.7 ng/dL ; P prostate-specific antigen or memory . Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study . Three of those seven withdrew because of an abnormal elevation in hematocrit . Testosterone supplementation improved strength , increased hemoglobin , and lowered leptin levels in older hypogonadal men . Testosterone may have a role in the treatment of frailty in males with hypogonadism ; however , older men receiving testosterone must be carefully monitored because of its potential risks", "Young adult males who can not produce or respond to estrogen ( E ) are osteopenic , suggesting that E may regulate bone turnover in men , as well as in women . Both bioavailable E and testosterone ( T ) decrease substantially in aging men , but it is unclear which deficiency is the more important factor contributing to the increased bone resorption and impaired bone formation that leads to their bone loss . Thus , we addressed this issue directly by eliminating endogenous T and E production in 59 elderly men ( mean age 68 years ) , study ing them first under conditions of physiologic T and E replacement and then assessing the impact on bone turnover of withdrawing both T and E , withdrawing only T , or only E , or continuing both . Bone resorption markers increased significantly in the absence of both hormones and were unchanged in men receiving both hormones . By two-factor ANOVA , E played the major role in preventing the increase in the bone resorption markers , whereas T had no significant effect . By contrast , serum osteocalcin , a bone formation marker , decreased in the absence of both hormones , and both E and T maintained osteocalcin levels . We conclude that in aging men , E is the dominant sex steroid regulating bone resorption , whereas both E and T are important in maintaining bone formation", "OBJECTIVE Testosterone deficiency is associated with significant morbidity , and and rogen replacement in overt hypogonadism is clearly beneficial . However , there are few data concerning the response to therapy in young men with mild testosterone deficiency" ]	411839ac-06ff-11f0-808a-c43d1ab1c353
Background Vitamin D might be promising to serve as an adjunctive therapy for pulmonary tuberculosis ( TB ) . However , the results remained controversial . We conducted a systematic review and meta- analysis to evaluate the efficacy and safety of vitamin D in patients with pulmonary TB . Methods Medline , SCOPUS , Google Scholar , EMBASE , Springer , and Science Direct were search ed electronically from inception to Oct 2016 . R and omized controlled trials ( RCTs ) and controlled clinical trials ( CCTs ) assessing the effect of vitamin D plus anti-tuberculosis treatment ( ATT ) versus placebo plus ATT on the treatment of pulmonary TB were included . Two investigators independently search ed articles , extracted data , and assessed the quality of included studies . Data were analyzed using RevMan 5.3 software . Results Five studies were included in this meta- analysis . Overall , compared with placebo intervention , vitamin D supplementation was found to have no significant effect on sputum smear negative conversion rates ( RR=0.99 ; 95 % CI=0.91 to 1.07 ; P=0.77 ) , BMI ( MD=0.11 ; 95 % CI=-0.85 to 1.07 ; P=0.82 ) and ESR ( MD=-2.29 ; 95 % CI=-8.87 to 4.30 ; P=0.50 ) . Conclusion Vitamin D supplementation showed no influence on the improvement of sputum smear-negative conversion rates and BMI , as well as the decrease in ESR	[ "Background Vitamin D ( vitD ) and L-arginine have important antimycobacterial effects in humans . Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis ( TB ) . Methods In a 4-arm r and omised , double-blind , placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis ( PTB ) in Timika , Indonesia , we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo , and L-arginine 6.0 g daily or matching placebo , for 8 weeks , on proportions of participants with negative 4-week sputum culture , and on an 8-week clinical score ( weight , FEV1 , cough , sputum , haemoptysis ) . All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned . Adults with new smear-positive PTB were eligible . The trial was registered at Clinical Trials.gov NCT00677339 . Results 200 participants were enrolled , less than the intended sample size : 50 received L-arginine + active vitD , 49 received L-arginine + placebo vit D , 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model , 99 people received arginine , 101 placebo arginine , 101 vitamin D , 99 placebo vitamin D. Results for the primary endpoints were available in 155 ( 4-week culture ) and 167 ( clinical score ) participants . Sputum culture conversion was achieved by week 4 in 48/76 ( 63 % ) participants in the active L-arginine versus 48/79 ( 61 % ) in placebo L-arginine arms ( risk difference −3 % , 95 % CI −19 to 13 % ) , and in 44/75 ( 59 % ) in the active vitD versus 52/80 ( 65 % ) in the placebo vitD arms ( risk difference 7 % , 95 % CI −9 to 22 % ) . The mean clinical outcome score also did not differ between study arms . There were no effects of the interventions on adverse event rates including hypercalcaemia , or other secondary outcomes . Conclusion Neither vitD nor L-arginine supplementation , at the doses administered and with the power attained , affected TB outcomes . Registry Clinical Trials.gov . Registry number :", "Background Vitamin D enhances host protective immune responses to Mycobacterium tuberculosis by suppressing Interferon-gamma ( IFN-g ) and reducing disease associated inflammation in the host . The objectives of this study were to determine whether vitamin D supplementation to patients with tuberculosis ( TB ) could influence recovery . Methods Two hundred and fifty nine patients with pulmonary TB were r and omized to receive either 600,000 IU of Intramuscular vitamin D3 or placebo for 2 doses . Assessment s were performed at 4 , 8 and 12 weeks . Early secreted and T cell activated 6 kDa ( ESAT6 ) and Mycobacterium tuberculosis sonicate ( MTBs ) antigen induced whole blood stimulated IFN-g responses were measured at 0 and 12 weeks . Statistical comparisons between outcome variables at 0 and 12 weeks were performed using Student ’s t-test and Chi2 tests . Results After 12 weeks , the vitamin D supplemented arm demonstrated significantly greater mean weight gain ( kg ) + 3.75 , ( 3.16 – 4.34 ) versus + 2.61 ( 95 % CI 1.99 – 3.23 ) p 0.009 and lesser residual disease by chest radiograph ; number of zones involved 1.35 v/s 1.82 p 0.004 ( 95 % CI 0.15 , 0.79 ) and 50 % or greater reduction in cavity size 106 ( 89.8 % ) v/s 111 ( 94.8 % ) , p 0.035 . Vitamin D supplementation led to significant increase in MTBs-induced IFN-g secretion in patients with baseline ‘ Deficient ’ 25-hydroxyvitamin D serum levels ( p 0.021 ) . Conclusions Supplementation with high doses of vitamin D accelerated clinical , radiographic improvement in all TB patients and increased host immune activation in patients with baseline ‘ Deficient ’ serum vitamin D levels . These results suggest a therapeutic role for vitamin D in the treatment of TB.Trial registration Clinical Trials.gov ; No. NCT01130311 ; URL : clinical", "Objectives Vitamin D is an immunomodulator and can alter response to tuberculosis ( TB ) treatment , though r and omised trials have been inconclusive to date . We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment , T-cell counts and nutritional outcomes by HIV status . Design Cohort study . Setting Outpatient clinics in Tanzania . Participants 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB ( 344 HIV infected ) initiating anti-TB treatment at enrolment in a multivitamin supplementation ( excluding vitamin D ) trial ( Clinical trials.gov identifier : NCT00197704 ) . Primary and secondary outcome measures Information on treatment outcomes such as failure and relapse , HIV disease progression , T-cell counts and anthropometry was collected routinely , with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients , respectively . Cox and binomial regression , and generalised estimating equations were used to assess the association of vitamin D status with these outcomes . Results Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 ( ±21.5 ) nmol/L ( 27.9 ( ±8.6 ) ng/mL ) . Vitamin D insufficiency ( higher risk of relapse ( 95 % CI 4 % to 164 % ; 133 % higher risk in HIV-uninfected patients ) . Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 ( p=0.004 ) CD8 and 3 ( p=0.01 ) CD3 T-cells/µL during follow-up in patients with HIV infection . Vitamin D insufficiency was also associated with a greater decrease of body mass index ( BMI ; –0.21 kg/m2 ; 95 % CI −0.39 to −0.02 ) , during the first 8 months of follow-up . No association was observed for vitamin D status with mortality or HIV disease progression . Conclusions Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB , with or without HIV infection . Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB", "RATIONALE Vitamin D was used to treat tuberculosis ( TB ) in the preantibiotic era . Prospect i ve studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed . OBJECTIVES To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status . METHODS A double-blind r and omized controlled trial was conducted in 192 healthy adult TB contacts in London , United Kingdom . Participants were r and omized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks . MEASUREMENTS AND MAIN RESULTS The primary outcome measure was assessed with a functional whole blood assay ( BCG-lux assay ) , which measures the ability of whole blood to restrict luminescence , and thus growth , of recombinant reporter mycobacteria in vitro ; the readout is expressed as a luminescence ratio ( luminescence postinfection/baseline luminescence ) . IFN-gamma responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay . Vitamin D supplementation significantly enhanced the ability of participants ' whole blood to restrict BCG-lux luminescence in vitro compared with placebo ( mean luminescence ratio at follow-up , 0.57 , vs. 0.71 , respectively ; 95 % confidence interval for difference , 0.01 - 0.25 ; p=0.03 ) but did not affect antigen-stimulated IFN-gamma secretion . CONCLUSIONS A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants ' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-gamma responses . Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection . Clinical trial registered with www . clinical trials.gov ( NCT 00157066 )", "The importance of nutrients for promotion of health and prevention of disease has long been recognized . Nonetheless , scientists are still trying to delineate the optimal intakes of various nutrients and their potential benefits for different population s. To that end , evidence -based medicine ( EBM ) has been applied to the study of nutrition . EBM methods basically call for the use of r and omized controlled trials ( RCTs ) to establish causal connection between the intervention and any particular endpoint . This paper focuses on problems that arise in the use of RCTS to establish a causal link between nutrients and various clinical endpoints . While many RCTS of calcium and vitamin D have been positive , many others have been None . In this paper , we discuss the reasons why effective nutrient agents may be found to be ineffective in particular studies , giving examples of such None results , and focusing on the nearly universal failure to consider biological criteria in design ing RCTs . Our purpose is ( 1 ) to inform future study design so as to ensure that relevant biological facts are considered and ( 2 ) to aid in the interpretation of the abundant , but often inconsistent literature on this topic", "BACKGROUND Vitamin D insufficiency is common in industrialized and developing nations . Recent studies have shown that vitamin D insufficiency is associated with a higher risk of active tuberculosis . Laboratory studies provided a mechanism for this link on the basis of findings that vitamin D metabolites regulate the expression of cathelicidin ( LL-37 ) , which is an endogenous antimicrobial peptide with activity against Mycobacterium tuberculosis . Little information is available on the clinical relation between vitamin D , LL-37 concentrations , and disease severity in patients with tuberculosis . OBJECTIVE The primary objective of the study was to evaluate the relation between vitamin D nutriture , serum LL-37 concentrations , and tuberculosis by using sample s stored in the Tuberculosis Trials Consortium serum repository . DESIGN We measured 25-hydroxyvitamin D [ 25(OH)D ] and LL-37 concentrations in 95 serum specimens from patients with culture-confirmed pulmonary tuberculosis and correlated these concentrations to clinical and demographic variables . RESULTS The prevalence of vitamin D insufficiency [ serum 25(OH)D concentration lt 30 ng/mL ] in patients with active tuberculosis was 86 % ( n = 95 ) with a mean baseline serum 25(OH)D concentration of 20.4 ng/mL. Factors associated with vitamin D insufficiency were black race and indoor lifestyle . The mean ( plusmn SD ) baseline LL-37 concentration was 49.5 plusmn 23.8 ng/mL. Higher LL-37 concentrations correlated with acid fast bacilli sputum smear positivity and weight gt 10 % below ideal body weight . Serum vitamin D status of the study subjects did not correlate with serum LL-37 concentrations . CONCLUSION More prospect ively design ed studies are needed to evaluate the clinical implication s of vitamin D insufficiency in patients with tuberculosis and the utility of circulating LL-37 as a potential biomarker in patients with active tuberculosis disease . The parent trial was registered at clinical trials.gov as NCT00023335", "AIM Diabetes and vitamin D deficiency are widely prevalent in India . Studies have proven correlation between low vitamin D levels and pulmonary tuberculosis ( PTB ) and low vitamin D levels and insulin resistance . We evaluated the effects of vitamin D supplementation on type 2 diabetes mellitus patients with pulmonary tuberculosis ( PTB ) . METHODS Forty-five subjects ( M : F=34:11 ) were screened . Inclusion criteria were age > 15 years , newly diagnosed PTB cases with uncontrolled diabetes , serum vitamin D The patients with vitamin D level were r and omly assigned to 2 groups . Group 1 subjects received oral cholecalceferol ( 60,000 units/week ) and calcium carbonate ( 1g/day ) along with anti tubercular treatment ( ATT ) , while group 2 subjects did not . Sputum was checked at interval of 2 weeks for 12 weeks . Primary end point was time to achieve sputum smear conversion . RESULTS Fifteen patients having vitamin D>20 ng/ml were excluded . Age of the patients was 42.9±13.2 years and serum vitamin D levels were 18.4±15.3 ng/ml . Sputum smear conversion was 6 weeks in group 1 versus 8 weeks in group 2 ( p=0.067 ) . Glycated hemoglobin levels reduced from 11.1±1.3 to 7.7±0.9 in group 1 versus 10.3±1.2 to 7.8±1.1 ( p>0.1 ) . CONCLUSION Vitamin D can serve as adjuvant treatment of tuberculosis in diabetics with vitamin D deficiency . Further studies are required to vali date this observation and define a cut off for vitamin D level to prevent immunological alterations", "BACKGROUND Tuberculosis , including multidrug-resistant tuberculosis ( MDR-TB ) , is a major global health problem . Individuals with tuberculosis disease commonly exhibit vitamin D deficiency , which may adversely affect immunity and the response to therapy . OBJECTIVE We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease . DESIGN The study was a double-blind , r and omized , placebo-controlled , intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi , Georgia . Subjects were r and omly assigned to receive oral vitamin D3 [ 50,000 IUs ( 1.25 mg ) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk ] or a placebo concomitant with st and ard first-line antituberculosis drugs . The primary outcome was the time for the conversion of a Mycobacterium tuberculosis ( Mtb ) sputum culture to negative . RESULTS Baseline characteristics between groups were similar . Most subjects ( 74 % ) were vitamin D deficient ( plasma 25-hydroxyvitamin D [ 25(OH)D ] concentration With vitamin D3 , plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16 . Adverse events and plasma calcium concentrations were similar between groups . In 192 subjects with culture-confirmed tuberculosis , an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [ 29 and 27 d , respectively ; HR : 0.86 ; 95 % CI : 0.63 , 1.18 ; P = 0.33 ) . Eight-week culture-conversion rates were also similar ( 84.0 % and 82.1 % for vitamin D3 and placebo , respectively ; P = 0.99 ) . CONCLUSION A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort . This trial was registered at clinical trials.gov at NCT00918086" ]	41183a2e-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Evidence about relevant outcomes is required in the evaluation of clinical interventions for children with autism spectrum disorders ( ASD ) . However , to date , the variety of outcome measurement tools being used , and lack of knowledge about the measurement properties of some , compromise conclusions regarding the most effective interventions . OBJECTIVES This two-stage systematic review aim ed to identify the tools used in studies evaluating interventions for anxiety for high-functioning children with ASD in middle childhood , and then to evaluate the tools for their appropriateness and measurement properties . METHODS Electronic data bases including Medline , PsychInfo , Embase , and the Cochrane data base and registers were search ed for anxiety intervention studies for children with ASD in middle childhood . Articles examining the measurement properties of the tools used were then search ed for using a method ological filter in PubMed , and the quality of the papers evaluated using the COSMIN checklist . RESULTS Ten intervention studies were identified in which six tools measuring anxiety and one of overall symptom change were used as primary outcomes . One further tool was included as it is recommended for st and ard use in UK children 's mental health services . Sixty three articles on the properties of the tools were evaluated for the quality of evidence , and the quality of the measurement properties of each tool was summarised . CONCLUSIONS Overall three question naires were found robust in their measurement properties , the Spence Children 's Anxiety Scale , its revised version - the Revised Children 's Anxiety and Depression Scale , and also the Screen for Child Anxiety Related Emotional Disorders . Crucially the articles on measurement properties provided almost no evidence on responsiveness to change , nor on the validity of use of the tools for evaluation of interventions for children with ASD . PROSPERO REGISTRATION NUMBER CRD42012002684	[ "Aim : To investigate the acceptability and feasibility of adapted group therapy for anxiety in children with autism spectrum disorder in a pilot r and omised controlled trial . Method : A total of 32 children aged 9–13 years were r and omised to immediate or delayed therapy using the ‘ Exploring Feelings ’ manual ( Attwood , 2004 ) . Child and parent groups were run in parallel , for seven weekly sessions , under the supervision of experienced psychologists . The primary blinded outcome measures addressed change in overall functioning and in severity of the primary anxiety diagnosis after 3 months . Results : Children met diagnostic criteria for 1–6 anxiety disorders ( median 3 ) . At end point , both parents and children in the immediate therapy group were more likely to report a reduction in anxiety symptoms . Fidelity of delivery of the group therapy was high , and attendance was 91 % . Conclusions : This pilot trial established that children and families were willing to be recruited and r and omised , the outcome measures were acceptable , the format and content of the groups were feasible within UK child and adolescent mental health services , the intervention was appreciated by families and attrition was very small", "BACKGROUND Children with high-functioning autism spectrum disorders ( ASD ) are at high risk for developing significant anxiety . Anxiety can adversely impact functioning across school , home and community environments . Cognitive behavioral therapies ( CBT ) are frequently used with success for children with anxiety symptoms . Modified CBT interventions for anxiety in children with ASD have also yielded promising results . METHODS Fifty children with high-functioning ASD and anxiety were r and omizedto group CBT or treatment-as-usual ( TAU ) for 12 weeks . Independent clinical evaluators , blind to condition , completed structured interviews ( Anxiety Disorders Interview Schedule – Parent Version;ADIS-P ) pre- and post-intervention condition . RESULTS Forty-seven children completed either the CBT or TAU condition . Results indicated markedly better outcomes for the CBT group . Significant differences by group were noted in Clinician Severity Ratings , diagnostic status , and clinician ratings of global improvement . In the intent-to-treat sample , 10 of 20 children ( 50 % ) in the CBT group had a clinical ly meaningful positive treatment response , compared to 2 of 23 children ( 8.7 % ) in the TAU group . CONCLUSIONS Initial results from this r and omized , design ed treatment study suggest that agroup CBT intervention specifically developed for children with ASD may be effective in decreasing anxiety . Limitations of this study include small sample size , lack of an attention control group , and use of outcome measures normed with typically developing", "This pilot study tested the effect of cognitive behavioral therapy ( CBT ) on parent-reported autism symptoms . Nineteen children with autism spectrum disorders and an anxiety disorder ( 7–11 years old ) were r and omly assigned to 16 sessions of CBT or a waitlist condition . The CBT program emphasized in vivo exposure supported by parent training and school consultation to promote social communication and emotion regulation skills . Parents completed a st and ardized autism symptom checklist at baseline and posttreatment/postwaitlist and 3-month follow-up assessment s. CBT outperformed the waitlist condition at posttreatment/postwaitlist on total parent-reported autism symptoms ( Cohen ’s d effect size = .77 ) . Treatment gains were maintained at 3-month follow-up . Further investigation of this intervention modality with larger sample s and broader outcome measures appears to be indicated", "OBJECTIVE A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request ( symptoms of most concern to patient/caregiver ) , which may be diluted in change scores of multisymptom scales . METHOD In the Research Units on Pediatric Psychopharmacology ( RUPP ) Autism Network 8-week double-blind trial of risperidone versus placebo , the chief concerns of parents were collected at 0 , 4 , and 8 weeks ( endpoint ) , in addition to st and ardized primary measures . Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale ( 1 = normalized , 5 = unchanged , 9 = disastrous ) ; 94 participants had usable data . RESULTS The most common symptoms identified by parents were tantrums , aggression , and hyperactivity . Interrater reliability was excellent . Mean ratings at endpoint were 2.8 + /- 1.2 on risperidone and 4.5 + /- 1.3 on placebo ( p Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale ( primary dimensional measure ) . Effect size d was 1.4 , compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale . Effect sizes varied twofold by symptom category , largest for self-injury ( 2.11 ) and tantrums ( 1.95 ) . CONCLUSIONS Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior . Rating individualized participant-chosen target symptoms seems a reliable , sensitive , efficient , and consumer-friendly way to assess treatment effect and might have clinical application", "OBJECTIVE To examine the reliability and validity of the 66-item Screen for Child Anxiety Related Emotional Disorders-Revised ( SCARED-R ) , a question naire for measuring a broad range of DSM-defined anxiety disorder symptoms , in a sample of clinical ly referred youths . METHOD The SCARED-R was administered to children/adolescents and their parents during the st and ard intake assessment . SCARED-R scores were compared against Child Behavior Checklist ( CBCL ) scores , DSM-IV axis I classifications , and global assessment of functioning ( GAF ) ratings . RESULTS In this sample of clinical ly referred youths , the SCARED-R was reliable in terms of internal consistency and showed reasonable child-parent agreement . Furthermore , SCARED-R scores correlated significantly with CBCL internalising but not with externalising . Within the group of children with anxiety disorders , SCARED-R scores were also negatively associated with children 's daily functioning as rated on the GAF scale . Finally , SCARED-R scores had satisfactory discriminant validity ( both between anxiety disorders and other problems and within anxiety disorders ) , and appeared to have reasonable value for predicting specific anxiety disorders . CONCLUSION The SCARED-R is a valuable addition to the arsenal of question naires that are used for the assessment of anxiety in youths", "Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields", "The goals of this study were twofold : to examine the psychometric properties of the Multidimensional Anxiety Scale for Children ( MASC ) in a clinical sample of 193 children and adolescents who had received a diagnosis of major depressive or anxiety disorder , and to discriminate between these two groups of patients . Participants had volunteered in r and omized psychopharmacological clinical trials . The MASC four-factor structure was confirmed and its subscales were found to be reliable . The MASC correlated well with other self-report measures of anxiety , and less so with measures of depressive symptoms . The MASC subscales and two MASC items as well as age differentiated between anxious and depressed pediatric patients . If these results are replicated in an independent study , those items could be used by clinicians to discriminate between these two disorders . The MASC is a clinical ly useful measure to discriminate between anxious and depressed pediatric patients . Limitations due to the highly selective sample are noted", "BACKGROUND Children with autism spectrum disorders often present with comorbid anxiety disorders that cause significant functional impairment . This study tested a modular cognitive behavioral therapy ( CBT ) program for children with this profile . A st and ard CBT program was augmented with multiple treatment components design ed to accommo date or remediate the social and adaptive skill deficits of children with ASD that could pose barriers to anxiety reduction . METHOD Forty children ( 7 - 11 years old ) were r and omly assigned to 16 sessions of CBT or a 3-month waitlist ( 36 completed treatment or waitlist ) . Therapists worked with individual families . The CBT model emphasized behavioral experimentation , parent-training , and school consultation . Independent evaluators blind to treatment condition conducted structured diagnostic interviews and parents and children completed anxiety symptom checklists at baseline and posttreatment/postwaitlist . RESULTS In intent-to-treat analyses , 78.5 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 8.7 % of the waitlist group . CBT also outperformed the waitlist on diagnostic outcomes and parent reports of child anxiety , but not children 's self-reports . Treatment gains were maintained at 3-month follow-up . CONCLUSIONS The CBT manual employed in this study is one of the first adaptations of an evidence -based treatment for children with autism spectrum disorders . Remission of anxiety disorders appears to be an achievable goal among high-functioning children with autism", "BACKGROUND The aim of the study was to evaluate the effectiveness of a brief CBT intervention for anxiety with children diagnosed with Asperger syndrome ( AS ) . A second interest was to evaluate whether more intensive parent involvement would increase the child 's ability to manage anxiety outside of the clinic setting . METHODS Seventy-one children aged ten to twelve years were recruited to participate in the anxiety programme . All children were diagnosed with AS and the presence of anxiety symptoms was accepted on parent report via brief interview . Children were r and omly assigned to one of three conditions : intervention for child only , intervention for child and parent , wait-list control . RESULTS The two intervention groups demonstrated significant decreases in parent-reported anxiety symptoms at follow-up and a significant increase in the child 's ability to generate positive strategies in an anxiety-provoking situation . There were a number of significant differences between the two interventions to suggest parent involvement as beneficial . CONCLUSIONS The sample of children with AS in this study presented with a profile of anxiety similar to a sample of clinical ly diagnosed anxious children . The intervention was endorsed by parents as a useful programme for children diagnosed with Asperger syndrome and exhibiting anxiety symptoms , and active parent involvement enhanced the usefulness of the programme . Limitations of the study and future research are discussed", "We compared the effects of a 16-week Cognitive-Behavioral Therapy ( CBT ) program and a Social Recreational ( SR ) program on anxiety in children with Autism Spectrum Disorders ( ASD ) . Seventy children ( 9–16 years old ) were r and omly assigned to either of the programs ( nCBT = 36 ; nSR = 34 ) . Measures on child ’s anxiety using the Spence Child Anxiety Scale — Child ( SCAS-C ) and the Clinical Global Impression — Severity scale ( CGI-S ) were administered at pre- , post-treatment , and follow-ups ( 3- and 6-month ) . Children in both programs showed significantly lower levels of generalized anxiety and total anxiety symptoms at 6-month follow-up on SCAS-C. Clinician ratings on the CGI-S demonstrated an increase in the percentage of participants rated as “ Normal ” and “ Borderline ” for both programs . Findings from the present study suggest factors such as regular sessions in a structured setting , consistent therapists , social exposure and the use of autism-friendly strategies are important components of an effective framework in the management of anxiety in children and adolescents with ASD", "OBJECTIVES The revised version of the Screen for Childhood Anxiety Related Emotional Disorders ( SCARED-R ) is a recently developed self-report question naire for measuring DSM-IV defined anxiety disorder symptoms in children . The current study examined the treatment sensitivity of the SCARED-R. METHODS Thirty-six children ( aged 8 - 13 years ) who fulfilled the criteria for generalized anxiety disorder , separation anxiety disorder , and /or social phobia received either group or individual cognitive-behavioural treatment . Children completed the SCARED-R and a traditional measure of childhood anxiety , the State-Trait Anxiety Inventory for Children ( STAIC ) , at three points in time : ( 1 ) 6 months before treatment ( i.e. baseline ) , ( 2 ) pre-treatment , and ( 3 ) post-treatment . RESULTS Results showed that children 's SCARED-R and STAIC scores did not change from baseline to pre-treatment , but significantly declined from pre-treatment to post-treatment . An additional finding of the present study was that group and individual CBT were equally effective in reducing children 's anxiety symptoms . CONCLUSIONS It can be concluded that the SCARED-R reliably taps treatment effects and thus should be regarded as a useful self-report index of childhood anxiety in clinical and research setting s. Furthermore , the data support the notion that CBT should be generally regarded as an efficacious intervention for anxiety disordered children", "We examined the test-retest reliability of the Multidimensional Anxiety Scale for Children ( MASC ) in a school-based sample of children and adolescents . One classroom at each grade from 3 to 12 was r and omly selected to participate . Teachers were trained to administer the MASC at baseline and again 3 weeks later . The intraclass correlation coefficient ( ICC ) was used to estimate stability of the MASC over time . For both single case and mean ICCs , the MASC exhibited satisfactory to excellent stability across all factors and subfactors . Stability was unaffected by age or gender , but was lower for African American than Caucasian subjects . Satisfactory test-retest reliability also was demonstrated for two empirically derived subscales , the MASC-10 and Anxiety Index" ]	41183aa6-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES Patient and public involvement ( PPI ) is argued to lead to higher quality health research , which is more relatable to and helps empower the public . We synthesis ed the evidence to look for examples of PPI in health research in low/middle-income countries ( LMICs ) , looking at levels of involvement and impact . Additionally , we considered the impact of who was undertaking the research on the level of involvement and reported impact . DESIGN Systematic review . DATA SOURCES EMBASE , Medline and PsychINFO , along with h and - search ing references , grey literature , Google search and expert advice . ELIGIBILITY CRITERIA Any health research with evidence of patient or public involvement , with no language restrictions date d from 1978 to 1 Dec 2017 . DATA EXTRACTION AND SYNTHESIS Data relating to stage and level of involvement , as well as impact , were extracted by one research er ( NC ) , and a coding framework was developed using an inductive approach to examine the impact of PPI on research . Extracted data were then independently coded by a second lay research er ( RK ) to vali date the data being collected . Discrepancies were referred to a third independent review er ( MT ) for review and consensus reached . RESULTS Sixty-two studies met the inclusion criteria . The review revealed the most common stage for PPI was in research planning , and the most common level of involvement was collaboration . Most studies did not provide evidence of effectiveness or elaborate on the impact of PPI , and they tended to report impact from the research er 's perspective . Where impact was mentioned , this generally related to increased relevance to the community , empowerment of participants and alterations in study design . CONCLUSIONS The literature describing approaches to and impact of PPI on LMIC health research is sparse . As PPI is essential to conducting high- quality research , it should be fully reported and evaluated at the end of the research project	[ "Participatory mapping and transect walks were used to inform the research and intervention design and to begin building community relations in preparation for Project Accept , a community-r and omized trial sponsored by the National Institute of Mental Health . Project Accept is being conducted at five sites in four countries : Thail and , Zimbabwe , South Africa , and Tanzania . Results from the mapping exercises informed decisions such as defining community boundaries and identifying appropriate criteria for matching community pairs for the trial as well as where to situate the services . The mapping also informed intervention-related decisions such as where to situate the services . The participatory methods enabled research ers at each site to develop an underst and ing of the communities that could not have been derived from existing data or data collected through st and ard data collection techniques . Furthermore , the methods lay the foundation for collaborative community research partnerships", "Community engagement is an on-going , arduous , and necessary process for developing effective health promotion programs . The challenges are amplified when the particular health issue or research question is not prominent in the consciousness of the targeted community . In this paper , we explore the community-based participatory research ( CBPR ) model as a means to negotiate a mutual agenda between communities and research ers . The paper is focused on the ( perceived ) need for cervical cancer screening in an under-re source d community in Cape Town , South Africa . Cervical cancer is a significant health problem in this community and elsewhere in South Africa . Unlike HIV-AIDS , however , many Black South Africans have not been educated about cervical cancer and the importance of obtaining screening . Many may not consider screening a priority in their lives . Our research included extensive consultations and informal interviews with diverse community and regional stakeholders . Following these , we conducted 27 focus groups and 106 demographic surveys with r and omly selected youth , parents , local health care personnel , educators and school staff . Focus group data were summarized and analyzed cross-sectionally . Community stakeholders were involved throughout this research . Our consultations , interviews , and focus group data were key in identifying the concerns and priorities of the community . By engaging community stakeholders , we developed a research framework that incorporated the community 's concerns and priorities , and stressed the intersecting roles of poverty , violence , and other cultural forces in shaping community members ' health and wellbeing . Community members helped to refocus our research from cervical cancer to ' cervical health , ' a concept that acknowledged the impact on women 's bodies and lives of HIV-AIDS and STDs , sexual violence , poverty , and multiple social problems . We conclude that the research agenda and questions in community-based health research should not be considered immutable . They need to be open to negotiation , creativity , and constant reinvention", "Background Community consultation is increasingly recommended , and in some cases , required by ethical review boards for research that involves higher levels of ethical risk such as international research and research with vulnerable population s. In design ing a r and omised control trial of a mental health intervention using a wait list control , we consulted the community where the research would be undertaken prior to finalising the study protocol . The study sites were two conflict-affected locations : Grozny in the Chechen Republic and Kitchanga in eastern Democratic Republic of Congo . Methods Group discussion s with a range of community members were held in both study sites . Facilitators used a prepared set of questions to guide the discussion s and to solicit feedback on the value of the research as well as on the study design . Specific questions were asked about enablers and barriers to participation in the research . Results Six groups were held in Grozny and thirteen in Kitchanga . The majority of individuals and groups consulted supported the research , and understood the purpose . In Grozny , the main concern raised was the length of the waiting period . Barriers to both waiting and returning for follow up were identified . In Kitchanga , there was a strong reaction against the wait list control and against r and omisation . The consultations provided information on unanticipated harms to the community , allowing changes to the study design to mitigate these harms and increase acceptability of the study . It also served to inform the community of the study , and through engaging with them early , helped promote legitimacy and joint responsibility . Conclusion Community consultation prior to finalising the study design for a mental health intervention trial in two humanitarian setting s proved feasible . Our experience reinforces the importance of community consultation before the study design is finalised and the importance of broad consultation that includes both community leaders and the potential study participants", " To determine the prevalence of drug abuse in city neighborhoods in a developing country undergoing rapid urbanization , we performed a household survey on the spread of drug abuse in Vientiane , Lao People 's Democratic Republic . A total of 1497 households from 17 villages were selected by the stratified r and om sampling method from urban districts in the city of Vientiane . Participatory style research was employed to increase both the sensitivity of detection and the reliability of information gathered . Local key players shared in the participatory process in this study . We worked with national and city officers and community leaders , as well as with neighborhood leaders who had received previous training for this survey , and conducted household surveys using face-to-face interviews . We inquired about the spread of drug abuse by asking if the families interviewed recognized drug abuse problems in their community . To examine the extent of urbanization of individual villages , the urban index was calculated by principle component analysis from the following eight indicators : income , occupation , parents ' educational histories , diffusion of telephones , ownership of livestock , diffusion of plumbing for running water and distance from the Vientiane city center to the village . Distance was calculated by the Geographic Information System . Among the 17 villages included in the study , the average percentage of recognition of drug abuse in the community was 63.2 % . The relationship between recognition of cases of drug abuse in the community and the urban index showed a significant correlation , with a Spearman coefficient of 0.650 ( p high reliability of participatory style surveys is also discussed . In conclusion , city neighborhoods in a developing country undergoing rapid urbanization showed evidence of the spread of drug abuse , which was associated with the urban index . Participatory style research activity was recommended to help raise awareness of community participation in anti-drug-abuse activities", "BACKGROUND There is an urgent need to develop effective strategies to improve stroke outcomes in Sub-Saharan Africa ( SSA ) , where use of evidence -based therapies among patients receiving conventional care is poor . Design s of behavioral interventions to improve stroke care in SSA need to be sensitive to both individual and community factors ( including local perceptions and public policies ) contributing to the likelihood of compliance with recommended therapeutic goals . This article presents a community-based participatory research protocol that will evaluate systems and processes affecting the continuum of stroke-preventive care in an SSA country . METHODS Phase 1 of the Tailored Hospital-based Risk Reduction to Impede Vascular Events study will be implemented from 2013 to 2014 at 4 different types of hospital setting s in Nigeria . Six adult stroke survivor focus group discussion s and six caregiver focus group discussion s , each lasting about 120 minutes will be conducted . Each group will comprise 6 to 8 participants . We will also conduct 22 semi-structured key informant interviews ( informed by the Theoretical Domains Framework ) with several types of providers and hospital administrators . Purposive and maximum variation sampling will be used to identify and recruit participants from participating hospitals . Transcript data will be analyzed by review ers in an iterative process to identify recurrent and unifying themes using a constructivist variant of the grounded theory methodology , and will involve participatory co- analysis with key stakeholders to enhance authenticity and veracity of findings . DISCUSSION On the basis of the results of Tailored Hospital-based Risk Reduction to Impede Vascular Events phase 1 , we intend to develop a culturally sensitive , system-appropriate , multipronged intervention whose efficacy to boost adherence to evidence -based stroke-preventive care will be tested in a future r and omized trial ( phase 2 )" ]	41183b14-06ff-11f0-808a-c43d1ab1c353
Background Xerosis , literally dryness of the skin , of the foot is a common condition encountered clinical ly , which can lead to discomfort and predisposition to infection . Currently , there are no evidence -based recommendations on which moisturiser formulations best alleviate xerotic symptoms . The aim of this review was to guide clinical practice in the treatment of primary and diabetes related foot xerosis , by identifying from the existing literature the most effective ingredient or formulation of topical treatments for symptoms of primary foot xerosis in the general population . Methods A systematic review of published experimental trials was undertaken . Only studies pertaining to primary xerosis , classified within levels II – IV of the NHRMC hierarchy were review ed . EMBASE , AMED , Cochrane , MEDLINE , CINAHL , Ageline and SCOPUS were search ed using relevant search terms and keywords and pearling of reference lists was undertaken . Studies were evaluated for method ological quality using a critical appraisal tool . Individual active ingredients were identified from all studies , along with observed reported outcomes . A narrative synthesis was then conducted . Results A total of 22 experimental studies were included , from which 12 different active ingredients were identified . Study literature consisted of mainly comparative studies against other active interventions or controls , or pre-post-tests and was of a poor-to-moderate method ological quality as assessed by the Epidemiological Appraisal Instrument . Urea was the most research ed active ingredient ( 14 studies ) , with ammonium lactate being next ( 7 studies ) . Conclusions No conclusive recommendations were possible due to wide variation in study quality , method ologies and outcome measures . A synthesis of available literature suggests that treatments containing urea as a primary active ingredient have been the most research ed . The poor quality of literature generally , however , precludes recommendation of any active ingredient over another	[ "The treatment for xerosis ( dry skin ) is the repeated use of moisturizers to hydrate the skin . Their use is based on sound evidence of the importance of maintaining the skin 's water content . Although the skin on the plantar surface of the foot is very thick , it is highly visco-elastic and copes with high levels of frictional , compressive and shear stresses applied to it by being supple and well hydrated . Problems arise when the skin becomes dry and loses its elastic properties . Fissures can occur which are often painful and can act as portals for infection . This article describes a double-blind clinical study to evaluate and compare the effectiveness of two commonly used moisturizers and to see if one was significantly better than the other at hydrating the skin of the feet . The two creams used were Aqueous Cream BP and CCS Foot Care Cream . Skin hydration levels were measured before any application of moisturizer and again after two weeks of twice daily application . Results showed that the regular use of both moisturizers had a significant hydrating effect on the skin . However , CCS Foot Care Cream had a significantly greater hydrating effect than Aqueous Cream BP", "AIM Xerosis is one of the most common abnormalities observed in the diabetic foot , promoting ulceration through the development of fissures and hyperkeratosis . Its treatment is therefore paramount and must be implemented early on . The objective of this study was to assess the moisturizing properties of Pédimed ( ® ) cream in the treatment of foot xerosis in diabetic patients . METHODS In this r and omized double-blind study , Pédimed ( ® ) and its placebo were r and omly allocated to the right/left foot of each patient ( one active/one control side ) . Products were applied twice daily for 4 weeks . Xerosis was assessed using the clinical Xerosis Assessment Scale ( XAS ) , corneometry ( skin hydration measurement ) and D-Squame ( ® ) ( scale sample analysis ) after 14 ( D14 ) and 28 ( D28 ) days of treatment . RESULTS Twenty-four men and 30 women , aged 57.0±12.7 years , with type 1 or type 2 diabetes and moderate-to-severe foot xerosis were included . A dramatic decrease in XAS score that was more marked with Pédimed ( ® ) than with placebo was observed from D14 ( 38.1 % vs 20.9 % , P . The number of feet with fissures was greatly reduced with Pédimed ( ® ) compared with placebo at both D14 ( 11.1 % vs 22.2 % , P=0.031 ) and D28 ( 5.6 % vs 18.5 % , P=0.039 ) . Skin hydration increased by 48.9 % with Pédimed ( ® ) vs 31.7 % with placebo at D14 ( P=0.0002 ) , reaching 57.3 % vs 36.5 % at D28 ( P All D-Squame ( ® ) parameters showed greater improvement with Pédimed ( ® ) . Product tolerability was excellent . CONCLUSION Vali date d clinical and para clinical tools demonstrated the efficacy of Pédimed ( ® ) in improving xerosis and reducing fissures of the feet in diabetic patients", "Background Xerosis is a common skin disorder frequently observed in diabetic patients . An effective hydration of foot skin in diabetics is a relevant preventive strategy in order to maintain a healthy foot . Urea is considered an effective hydrating and emollient topical product . The aim of the present study was to evaluate the efficacy of topical urea 5 % with arginine and carnosine ( Ureadin Rx Db , ISDIN Spain ) ( UC ) in comparison with glycerol-based emollient topical product ( Dexeryl , Pierre Fabre ) ( EC ) , in Type 2 diabetic patients . Methods We assessed the effect of UC on skin hydration in a r and omized , evaluator-blinded comparative study in 40 type II diabetic patients , aged 40–75 years , treated with UC or the comparator for 28 days with a twice-daily application . The principal outcomes were the Dryness Area Severity Index ( DASI ) Score and the Visual Analogue Score ( VAS ) for skin dryness evaluated at baseline and at the end of study period by an investigator unaware of treatment allocation . Results UC induced significantly greater hydration than EC with an 89 % reduction in DASI score ( from 1.6 to 0.2 ; p , DASI score in UC treated group was significantly lower ( 0.2 vs. 1.0 ; p = 0.048 ) . VAS score ( high values mean better hydration ) significantly increased in both groups during treatment . VAS score at the end of treatment period was significantly higher in UC group in comparison with EC group ( 9.8 vs. 8.2 ; p = 0.05 ) . Conclusion Application of urea 5 % , arginine and carnosine cream increases skin hydration and alleviates the condition of skin dryness in Type 2 diabetic patients in comparison with a control glycerol-based emollient product . ( Dutch Trials Register trial number 3328 )", "Two emollients , ammonium lactate 12 % lotion and a liposome-based moisturizing lotion , were compared in a double-blind test for efficacy in the treatment of plantar xerosis . A total of 43 out of 57 participants ( 75 % ) with bilateral plantar xerosis followed instructions completely and applied the lotions ( one to each foot ) twice daily for 4 weeks . Each participant was evaluated once a week for 6 weeks ( the final 2 weeks for evaluation of post-treatment regression ) to determine xerotic grade ( degree of dryness ) and treatment effectiveness . With both lotions , significant improvement began during the second week of treatment and continued into the fourth week . There were no significant differences between the two lotions in the 6-week patterns of either xerotic grade or treatment effectiveness", "Abstract Background : Urea and ammonium lactate are used for the treatment of xerosis , with different degrees of success . This study compares the clinical effectiveness of these two agents . Objective : To compare the effectiveness and tolerance of a 40 % urea topical cream (Carmol ® 40)1 from Doak Dermatologics , a subsidiary of Bradley Pharmaceuticals , Inc. , and 12 % ammonium lactate topical lotion ( Lac-Hydrin ® 12 % ) from Westwood Squibb , a division of Bristol-Myers Squibb . Methods : A r and omized , double-blind , bilateral paired comparison study was conducted involving 25 men and women who were undergoing treatment for moderate to severe xerosis . The study included evaluations upon initiation of the study , after a 14-day treatment period and treatment follow-up on day 28 . Results : Eighteen study participants completed the entire 28-day evaluation period . Evaluation of treatment benefit was based on instrumental measurement of water loss from the skin surface , skin capacitance , skin desquamation , skin roughness , subject self assessment of skin and investigator evaluation . Results indicated that clinical observation ratings by patients and investigators , as well as instrument measures , show differences between the two treatments . Most measures show that improvement is achieved in less time with 40 % urea cream than with 12 % ammonium lactate lotion . On day 14 , the 40 % urea cream was superior to the 12 % ammonium lactate lotion as measured by skin roughness , fissure reduction , thickness and dryness . Discussion : At day 14 of treatment , 40 % urea cream was superior to 12 % ammonium lactate for most of the instrumental and clinical assessment", "Xerosis is frequently noted in the feet of people with diabetes . The presence of xerosis increases the risk of complications , including infection and ulceration , making it imperative to counteract its effects . A prospect i ve , r and omized , controlled double-blind study was conducted to compare the efficacy of a test moisturizer containing 10 % urea and 4 % lactic acid versus its emulsion base vehicle in the treatment of xerosis of the feet in patients with diabetes . Forty patients ( mean age 62 + /- 11 years ) with diabetes and moderate-to-severe xerosis of both feet were enrolled . Xerosis severity was assessed using a nine-point Xerosis Assessment Scale . The tested moisturizer was applied to one foot and the vehicle to the other , twice a day , for 4 weeks . The regression of xerosis also was evaluated 2 weeks following discontinuation of the treatments . Progress was noted weekly with photographs and examination . Feet treated with the vehicle cream ( control ) had an initial mean xerosis grading of 6.17 ( + /- 0.79 ) and a final xerosis grading of 4.38 ( + /- 2.20 ) . In the treatment group , mean xerosis grading diminished from 6.13 ( + /- 0.73 ) to 3.19 ( + /- 2.23 ) after 4 weeks ( P moderate-to-severe xerosis of the feet in patients with diabetes . The cream containing 10 % urea and 4 % lactic acid provided faster and better improvement with significantly less xerosis regression", "BACKGROUND Moisturizers are often used to overcome dry skin conditions . However , cosmetic moisturizers may lack in efficiency and may also deteriorate skin barrier function . The objective of this study was to generate data on a new humectant-rich formulation ( 15 % alfahydroxy acids and 15 % urea ) in the treatment of normal skin as well as in dry feet with hyperkeratosis and cracked skin with fissures . Changes in permeability and effectiveness of the product after once- and twice-daily applications to the feet will be monitored . METHODS The study was r and omized , bilateral , controlled and evaluator-blind . The first part of the study included 12 healthy volunteers and the second part 50 patients with hyperkeratotic feet . The changes in the skin was evaluated by an expert , the patients and using non-invasive biophysical measurements of skin barrier function ( transepidermal water loss , TEWL ) , erythema , thickness ( ultrasound ) and hydration ( conductance ) . RESULTS The humectant-rich formulation increased skin hydration , removed scales and reduced thickness of hyperkeratotic skin . Skin barrier function was improved in normal skin , but no changes in TEWL were noted in the feet . No difference between once and twice-daily applications was found . Some smarting and stinging was noted . CONCLUSION The humectant-rich formulation efficiently relieved the xerosis on the feet without inducing any weakening of the skin barrier function . Instead the normal skin became more resistant to external insults by the treatment", "Xerotic skin is a pattern of reaction to a variety of disorders ( eg , winter xerosis , hereditary ichthyosis ) with abnormalities of desquamation in common . The trial described in this article was a double-blind r and omized-comparison clinical trial investigating the effect of pure lanolin versus ammonium lactate 12 % cream in treating moderate to severe foot xerosis . Xerosis was clinical ly assessed at baseline visit , and design ated sites were reevaluated after 1 , 2 , and 4 weeks of therapy . Ninety-two patients were enrolled ; 41 of these were excluded from analysis ( 25 were lost to follow-up , 8 were noncompliant , 1 was discharged from study because of an adverse event after visit 1 , and 7 were noncompliant after visit 2 ) . Although there was significant improvement in xerosis scores for both treatment groups after 2 and 4 weeks of treatment , no differences were statistically significant . Used twice daily for 4 weeks , pure lanolin and ammonium lactate cream were both effective in treating moderate to severe xerosis", "Background : Corneocyte accumulation ( hyperkeratosis , xerosis ) commonly occurs in the stratum corneum ( SC ) of the feet of diabetic patients , as well as menopausal women . Objective : To compare the effects of a 1.5 % chitin-glucan formulation with its placebo , and commercially available glycerol formulations . Methods : This two-step controlled double-blind , r and omized , intra-individual study was performed in 30 type 1 and 2 diabetic menopausal women suffering from xerosis of the feet . The formulations were applied once daily for 3 weeks . Electrometric assessment s were performed on three sites of the feet at entry in the study , at weekly intervals during the treatment phase , and in a 2-week follow-up out of treatment . Positive controls consisted in two commercially available formulations enriched in glycerol . Results : Data revealed an unequivocal benefit provided by the 1.5 % chitin-glucan formulation compared with placebo . The electrometric values were significantly higher at each evaluation time during both treatment and follow-up phases . The two glycerol-enriched formulations showed slightly different kinetics of SC moisturization . A steep increase was followed by a plateau level and a rapid decline after stopping the treatments . Conclusion : The increased moisturization of the SC of the sole probably improves the desquamation process and reduces xerosis of the soles ", "Xerotic skin is a pattern of reaction to a variety of disorders that have abnormalities of desquamation in common . This double-blind , r and omized clinical trial investigated the effect of Lactinol ( Pedinol Pharmaceuticals , Farmingdale , New York ) versus Lac-Hydrin 12 % ( Bristol-Myers Squibb , Princeton , New Jersey ) lotion in mild to moderate foot xerosis . Clinical assessment of xerosis was performed at baseline visit , and the design ated sites were evaluated at 2 and 4 weeks after treatment began . Of the 53 patients enrolled , 18 were excluded from analysis . Although both treatment groups had significantly improved xerosis scores after 2 and 4 weeks of treatment , no statistically significant difference was observed . Of the 44 % of patients who did express a preference , 72 % preferred Lactinol , which may account for the 20 % increase in its overall use in the study", "Xerosis is defined as dehydration of skin characterized by redness , dry scaling , and fine crackling that may resemble the crackling of porcelain . The present double-blind trial was a r and omized paired comparison study evaluating the keratolytic effect of 5 % salicylic acid and 10 % urea ointment ( Kerasal ) on one foot and 12 % ammonium lactate lotion ( Lac-Hydrin ) on the other foot in mild-to-moderate xerosis . Seventy patients were initially enrolled in the trial . Fifty-four patients were evaluated after 2 weeks of treatment ; of those 54 patients , 39 were evaluated after 4 weeks of treatment . Although there was significant improvement in severity of xerosis after 2 and 4 weeks of treatment , there was no statistically significant difference between treatment groups . Irrespective of the mechanism of action , this study shows that both Kerasal and Lac-Hydrin 12 % lotion result in reduction in the severity of xerosis after 4 weeks of therapy" ]	41183b96-06ff-11f0-808a-c43d1ab1c353
Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of " low testosterone " ( low-T ) for cardiovascular health , sexual function , muscle weakness or wasting , mood and behavior , and cognition . We performed a systematic review of 156 eligible r and omized controlled trials in which testosterone was compared to placebo for one or more of these conditions . We included studies in bibliographic data bases between January 1 , 1950 and April 9 , 2016 , and excluded studies involving bodybuilding , contraceptive effectiveness , or treatment of any condition in women or children . Studies with multiple relevant endpoints were included in all relevant tables . Testosterone supplementation did not show consistent benefit for cardiovascular risk , sexual function , mood and behavior , or cognition . Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo . Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido . Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function . Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality , psychological well-being , or mood . The prescription of testosterone supplementation for low-T for cardiovascular health , sexual function , physical function , mood , or cognitive function is without support from r and omized clinical trials	[ "Testosterone has immune-modulating properties , and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha , IL-1beta , and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10 . We report a r and omized , single-blind , placebo-controlled , crossover study of testosterone replacement ( Sustanon 100 ) vs. placebo in 27 men ( age , 62 + /- 9 yr ) with symptomatic and rogen deficiency ( total testosterone , 4.4 + /- 1.2 nmol/liter ; bioavailable testosterone , 2.4 + /- 1.1 nmol/liter ) . Compared with placebo , testosterone induced reductions in TNFalpha ( -3.1 + /- 8.3 vs. 1.3 + /- 5.2 pg/ml ; P = 0.01 ) and IL-1beta ( -0.14 + /- 0.32 vs. 0.18 + /- 0.55 pg/ml ; P = 0.08 ) and an increase in IL-10 ( 0.33 + /- 1.8 vs. -1.1 + /- 3.0 pg/ml ; P = 0.01 ) ; the reductions of TNFalpha and IL-1beta were positively correlated ( r(S ) = 0.588 ; P = 0.003 ) . In addition , a significant reduction in total cholesterol was recorded with testosterone therapy ( -0.25 + /- 0.4 vs. -0.004 + /- 0.4 mmol/liter ; P = 0.04 ) . In conclusion , testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol . Twenty of these men had established coronary disease , and because total cholesterol is a cardiovascular risk factor , and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque , these properties may have particular relevance in men with overt vascular disease", "CONTEXT Low T levels have been associated with ejaculatory dysfunction ( EjD ) in cross-sectional studies ; however , the efficacy of T replacement in improving EjD has not been studied in a r and omized controlled trial . OBJECTIVE To evaluate the efficacy of T replacement in and rogen-deficient men with EjD. DESIGN A multicenter , double-blind , r and omized , placebo-controlled , 16-week trial with T solution 2 % versus placebo . SETTING Medical centers in the United States , Canada , and Mexico . PATIENTS OR OTHER PARTICIPANTS Seventy-six men with one or more EjD symptoms , including delayed ejaculation , anejaculation , reduced ejaculate volume , and /or reduced force of ejaculation , and two total T levels with liquid chromatography t and em mass spectrometry . INTERVENTIONS Sixty milligrams of T solution 2 % or placebo applied to the axillae for 16 weeks . MAIN OUTCOME MEASURES The primary outcome was a change in the score of the three-item Male Sexual Health Question naire-Ejaculatory Dysfunction-Short Form ( MSHQ-EjD-SF ) ; secondary outcomes included measured ejaculate volume , scores of the bother/satisfaction item of the MSHQ-EjD-SF , the orgasmic function domain of the International Index of Erectile Function Question naire , and the sexual activity log . RESULTS Seventy-six participants were r and omized ; 66 completed the study . Baseline demographic and clinical characteristics were comparable between the treatment arms . T replacement improved the MSHQ-EjD-SF score ( mean score change , + 3.1 ) ; however , this effect was not statistically different from placebo ( mean score change , + 2.5 ; P = .596 ) . No differences were seen in any of the secondary outcomes or frequency of adverse events . CONCLUSION T replacement was not associated with significant improvement in EjD in and rogen-deficient men", "Objective —Because male sex is an independent risk factor for the severity of atherosclerosis , it is possible that and rogens may be proatherogenic . There is evidence that sex hormones , particularly estrogens , regulate ( or modulate ) inflammation , a process integral to atherogenesis . Because levels of serum inflammatory markers predict cardiovascular outcomes , we prospect ively assessed the effects of and rogen therapy on these markers in older men . Methods and Results —Levels of high-sensitivity C-reactive protein ( CRP ) , soluble intracellular adhesion molecule-1 ( sICAM-1 ) , and soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) were measured from sera collected at baseline and at the end of 2 r and omized double-blind placebo-controlled trials evaluating the effects of 3 months of and rogen treatment with either dihydrotestosterone ( DHT ) or recombinant human chorionic gonadotropin ( rhCG ) in healthy men aged > 60 years with partial and rogen deficiency ( serum testosterone levels For the DHT study ( 70 mg transdermally daily ) , 33 men completed 3 months of treatment ( 16 men were treated with DHT , and there were 17 controls ) . For the rhCG ( 250 & mgr;g twice weekly ) study , 20 men were treated with rhCG , and there were 20 controls . In both studies , groups were well matched for age and vascular risk factors . And rogen levels ( DHT and testosterone ) were consistently maintained at eugonadal levels throughout the trials , with estradiol markedly increased by rhCG but not DHT . Baseline CRP levels were 0.74 to 1.49 mg/L , sVCAM-1 levels were 847 to 950 ng/mL , and sICAM-1 levels were 256 to 292 ng/mL in all groups . Neither DHT nor rhCG result ed in significant changes in CRP , sVCAM-1 , or sICAM-1 compared with placebo ( P > 0.3 in both studies ) . Conclusions —Exogenous and rogen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men ; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women . These data provide a measure of reassurance concerning potential adverse cardiovascular effects of and rogen therapy in older men", "CONTEXT Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation . Trial 's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm . The changes in muscle performance and physical function were evaluated in relation to participant 's perception of change . METHODS Men aged 65 years and older , with mobility limitation , total testosterone 100 - 350 ng/dL , or free testosterone less than 50 pg/mL , were r and omized to placebo or 10 g testosterone gel daily for 6 months . Primary outcome was leg-press strength . Secondary outcomes included chest-press strength , stair-climb , 40-m walk , muscle mass , physical activity , self-reported function , and fatigue . Proportions of participants exceeding minimally important difference in study arms were compared . RESULTS Of 209 r and omized participants , 165 had follow-up efficacy measures . Mean ( SD ) age was 74 ( 5.4 ) years and short physical performance battery score 7.7 ( 1.4 ) . Testosterone arm exhibited greater improvements in leg-press strength , chest-press strength and power , and loaded stair-climb than placebo . Compared with placebo , significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths ( 43 % vs 18 % , p = .01 ) and stair-climbing power ( 28 % vs 10 % , p = .03 ) more than minimally important difference . Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass . Physical activity , walking speed , self-reported function , and fatigue did not change . CONCLUSIONS Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power . Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population", "The elevated estradiol/testosterone ( E2/T ) ratio had been proved to be a risk factor for coronary heart disease ( CHD ) in elderly men . We conducted a r and omized placebo controlled crossover study on the effects of a new and rogenic preparation \" And riol \" in 62 elderly men with CHD over a period of 2.5 months . The results showed significant differences between And riol- and placebo-treated groups at the end of this period : in the former , serum T level was elevated significantly ( P E2 level was unchanged ( P > 0.05 ) , E2/T ratio was reduced ( P angina pectoris ( AP ) was relieved ( total effective rate , 77.4 % ) , and myocardial ischemia in ECG and Holter recordings were improved ( total effective rate , respectively 68.8 % and 75 % ) . Doppler echocardiography showed that 12 parameters of cardiac function were unchanged in both groups . No obvious side effect was found in those who took And riol", "The prospect s of wider application of testosterone ( T ) in novel indications such as male contraception have prompted renewed interest in the investigation of nonreproductive actions and safety of and rogens . This study investigated potential changes in mood and behavior in response to elevations in circulating T concentrations produced by the new long-acting preparation , T undecanoate ( TU ) . Twenty-eight eugonadal men were r and omized into one of two treatment groups : A1 ) active , receiving 1000 mg TU i.m . followed by A2 ) washout , followed by A3 ) placebo , receiving 4 ml castor oil i.m . ; B1 ) placebo , 4 ml castor oil i.m . ; B2 ) washout followed by B3 ) active , receiving 1000 mg TU i.m .. Mood , self- and partner-reported physical and verbal aggression , anger , hostility , irritability , assertiveness , self-esteem , and sexual function were assessed . A single injection of 1000 mg TU i.m . increased plasma T concentrations from 20.7 + /- 1.5 to 37.5 + /- 2.2 nmol/liter at wk 1 and 31.6 + /- 1.5 nmol/liter at wk 2 , and estradiol from 74.0 + /- 4.9 to 120.4 + /- 10.7 pmol/liter at wk 1 , and 100.0 + /- 6.3 pmol/liter at wk 2 . The T increment was associated with detectable but minor mood changes . Increased circulating T was associated with significant increases in anger-hostility from baseline ( mean score = 7.48 ) to wk 2 ( mean score = 10.71 ) accompanied by an overall reduction in fatigue-inertia ( treatment = 6.21 vs. placebo = 7.84 ) . TU treatment did not increase aggressive behavior or induce any changes in nonaggressive or sexual behavior . Changes in estradiol were not associated with any behavioral alterations . Our results suggest that exogenous TU-induced elevation of circulating T , to the range likely to be used in hormonal male contraception , has limited psychological effects . Future research should investigate the implication s of these minor mood changes", "OBJECTIVE To assess the effect of short-term testosterone supplementation on health-related quality of life in elderly males . METHOD As part of a double-blind , placebo-controlled study , healthy males > or = 65-year-old were r and omised to receive a total of four doses of 200 mg testosterone enanthanate ( n = 14 ) or placebo ( n = 8) intramuscularly every 2 weeks . Health-related quality of life ( HRQOL ) was assessed using the Short Form 36-item ( SF-36 ) and Psychological General Well-Being ( PGWB ) scales , at baseline , week 8 and during therapy withdrawal , 6 weeks after the last dose . RESULTS The baseline SF-36 scores were similar between the groups in seven domains ; only vitality was significantly lower in the placebo group ( T : 80.4 , P : 65.6 ; P = 0.007 ) . After the 8-week treatment period and withdrawal phase , SF-36 scores were not significantly different between the groups . The PGWB scores at baseline , on treatment and off treatment were not significantly different between the groups . Moreover , the SF-36 and PGWB scores within each group did not change significantly over time . CONCLUSION This pilot study suggests that intramuscular testosterone , administered at a dose of 200 mg every 2 weeks , does not affect the HRQOL of elderly males", "OBJECTIVE Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men . Furthermore , there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men . Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance . We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein ( CRP ) in type 2 diabetic men . DESIGN Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men . Patients were treated with testosterone ( sustanon 200 mg ) or placebo intramuscularly every 2 weeks for 3 months in r and om order followed by a washout period of 1 month before the alternate treatment phase . METHODS Leptin , adiponectin , resistin , tumour necrosis factor-alpha ( TNF-alpha ) , interleukin (IL)-6 and CRP levels were measured before and after each treatment phase . Body mass index ( BMI ) and waist circumference were also recorded . RESULTS At baseline , leptin levels significantly correlated with BMI and waist circumference . There was a significant inverse correlation between baseline IL-6 and total testosterone ( r=-0.68 ; P=0.002 ) and bioavailable testosterone levels ( r=-0.73 ; P=0.007 ) . CRP levels also correlated significantly with total testosterone levels ( r=-0.59 ; P=0.01 ) . Testosterone treatment reduced leptin ( -7141.9 + /- 1461.8 pg/ml ; P=0.0001 ) and adiponectin levels ( -2075.8 + /- 852.3 ng/ml ; P=0.02 ) . There was a significant reduction in waist circumference . No significant effects of testosterone therapy on resistin , TNF-alpha , IL-6 or CRP levels were observed . CONCLUSION Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men . Moreover , low levels of testosterone in men are associated with pro-inflammatory profile , though testosterone treatment over 3 months had no effect on inflammatory markers", "Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy", "BACKGROUND The role of testosterone on the development of coronary artery disease in men is controversial . The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone . Conversely , recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men . Accordingly , the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men . METHODS AND RESULTS After withdrawal of antianginal therapy , 14 men ( mean age , 58+/-4 years ) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days ( baseline and either testosterone or placebo given in a r and om order ) . The exercise tests were performed 30 minutes after administration of testosterone ( 2.5 mg IV in 5 minutes ) or placebo . All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo , whereas only 10 patients had a positive exercise test after testosterone . Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone . Compared with placebo , testosterone increased time to 1-mm ST-segment depression ( 579+/-204 versus 471+/-210 seconds ; P total exercise time ( 631+/-180 versus 541+/-204 seconds ; P Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression ( 135+/-12 versus 123+/-14 bpm ; P peak exercise ( 140+/-12 versus 132+/-12 bpm ; P rate-pressure product at the onset of 1-mm ST-segment depression ( 24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm ; P peak exercise ( 26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm ; P testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease . This effect may be related to a direct coronary-relaxing effect", "Introduction : This study investigated the effects of testosterone ( T ) treatment on cognition , mood , and quality of life in men with mild cognitive impairment ( MCI ) and low serum T levels . Methods : A total of 351 community-dwelling men were screened , and 37 men evidence d both MCI and low T of whom 27 agreed for further screening . Twenty-two met all the study inclusion /exclusion criteria and enrolled in a 6-month r and omized , double-blind , placebo-controlled study . Results : Total T levels significantly increased in the T treatment group . No significant changes were observed in measures of cognition , mood , or quality of life other than improvement in 1 objective measure of verbal memory ( P decreased depression symptoms ( P Testosterone treatment may modestly improve verbal memory and depression symptoms in men with both MCI and low", " Acute administration of high-dose testosterone in men with coronary artery disease improves endothelial function", "CONTEXT The Heart and Estrogen/progestin Replacement Study ( HERS ) found no overall reduction in risk of coronary heart disease ( CHD ) events among postmenopausal women with CHD . However , in the hormone group , findings did suggest a higher risk of CHD events during the first year , and a decreased risk during years 3 to 5 . OBJECTIVE To determine if the risk reduction observed in the later years of HERS persisted and result ed in an overall reduced risk of CHD events with additional years of follow-up . DESIGN AND SETTING R and omized , blinded , placebo-controlled trial of 4.1 years ' duration ( HERS ) and subsequent unblinded follow-up for 2.7 years ( HERS II ) conducted at outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS ; 2321 women ( 93 % of those surviving ) consented to follow-up in HERS II . INTERVENTION Participants were r and omly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate ( n = 1380 ) , or placebo ( n = 1383 ) during HERS ; open-label hormone therapy was prescribed at personal physicians ' discretion during HERS II . The proportions with at least 80 % adherence to hormones declined from 81 % ( year 1 ) to 45 % ( year 6 ) in the hormone group , and increased from 0 % ( year 1 ) to 8 % ( year 6 ) in the placebo group . MAIN OUTCOME MEASURES The primary outcome was nonfatal myocardial infa rct ion and CHD death . Secondary cardiovascular events were coronary revascularization , hospitalization for unstable angina or congestive heart failure , nonfatal ventricular arrhythmia , sudden death , stroke or transient ischemic attack , and peripheral arterial disease . RESULTS There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS , HERS II , or overall . The unadjusted relative hazard ( RH ) for CHD events in HERS was 0.99 ( 95 % confidence interval [ CI ] , 0.81 - 1.22 ) ; HERS II , 1.00 ( 95 % CI , 0.77 - 1.29 ) ; and overall , 0.99 ( 0.84 - 1.17 ) . The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups ( RH , 0.97 ; 95 % CI , 0.82 - 1.14 ) , and in analyses restricted to women who were adherent to r and omized treatment assignment ( RH , 0.96 ; 95 % CI , 0.77 - 1.19 ) . CONCLUSIONS Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up . After 6.8 years , hormone therapy did not reduce risk of cardiovascular events in women with CHD . Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD", "How do human beings decide when to be selfish or selfless ? In this study , we gave testosterone to 25 men to establish its impact on prosocial behaviors in a double-blind within-subjects design . We also confirmed participants ' testosterone levels before and after treatment through blood draws . Using the Ultimatum Game from behavioral economics , we find that men with artificially raised T , compared to themselves on placebo , were 27 % less generous towards strangers with money they controlled ( 95 % CI placebo : ( 1.70 , 2.72 ) ; 95 % CI T : ( .98 , 2.30 ) ) . This effect scales with a man 's level of total- , free- , and dihydro-testosterone ( DHT ) . Men in the lowest decile of DHT were 560 % more generous than men in the highest decile of DHT . We also found that men with elevated testosterone were more likely to use their own money punish those who were ungenerous toward them . Our results continue to hold after controlling for altruism . We conclude that elevated testosterone causes men to behave antisocially", "Testosterone increases fat-free mass ( FFM ) in men infected with human immunodeficiency virus ( HIV ) , but its effects on muscle performance , physical function , mood , and quality of life are poorly understood . Sixty-one HIV-infected men with weight loss were r and omized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk . The primary outcome of interest was physical function ( walking speed , stair-climbing power , and load-carrying ability ) . Secondary outcome measures included body weight and composition , muscle performance , sexual function , mood , and quality of life . Serum nadir free and total testosterone levels increased ( + 188.0 + /- 29.6 and + 720 + /- 86 ng/dl ) in the testosterone , but not placebo , group . Testosterone administration was associated with increased FFM ( 2.8 + /- 0.5 kg ) , which was significantly greater than in the placebo group ( P Leg press strength increased significantly in testosterone-treated ( P = 0.027 ) , but not placebo-treated , men ; the difference between groups was not significant . Other measures of muscle performance and physical function did not change significantly in either group . Men receiving testosterone demonstrated significantly greater improvements in mental health and quality -of-life scores than those receiving placebo and improvements in fatigue/energy and mood scores that were not significantly different from those receiving placebo . Sexual function scores did not change in either group . In HIV-infected men with weight loss , a supraphysiological dose of testosterone significantly increased FFM but did not improve self-reported or performance-based measures of physical function . Improvements in mood , fatigue , and quality -of-life measures in the testosterone group , although clinical ly important , need further confirmation", "The effects of supraphysiological levels of testosterone , used for male contraception , on sexual behavior and mood were studied in a single-blind , placebo-controlled manner in a group of 31 normal men . After 4 weeks of baseline observations , the men were r and omized into two groups : one group received 200 mg testosterone enanthate ( TE ) weekly by i m injection for 8 weeks ( Testosterone Only group ) , the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks ( Placebo/Testosterone group ) . The testosterone administration increased trough plasma testosterone levels by 80 % , compatible with peak testosterone levels 400 - 500 % above baseline . Various aspects of sexuality were assessed using sexuality experience scales ( SES ) question naires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales . In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES ( i.e. SES 2 ) following testosterone administration , but not with placebo . There were no changes in SES 3 , which measures aspects of sexual interaction with the partner . In both groups there were no changes in frequency of sexual intercourse , masturbation , or penile erection on waking nor in any of the moods reported . The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo . The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone . However , these changes are not reflected in modifications of overt sexual behavior , which in eugonadal men may be more determined by sexual relationship factors . This contrasts with hypogonadal men , in whom testosterone replacement clearly stimulates sexual behavior . There was no evidence to suggest an alteration in any of the mood states studied , in particular those associated with increased aggression . We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships . Raising testosterone does not increase self-reported ratings of aggressive feelings", "Hypogonadism is prevalent among human immunodeficiency virus-infected men , in whom significantly reduced quality of life and mood disturbances have been reported . Previous studies have not investigated the relationship between depression score and gonadal function among such patients . We first compared depression scores in hypogonadal ( n = 52 ) and eugonadal ( n = 10 ) patients with acquired immunodeficiency syndrome ( AIDS ) wasting , matched for weight and disease status , and then investigated the effects of testosterone administration on depression score in a r and omized , double-blind , placebo-controlled study among the group of hypogonadal men with AIDS wasting . The primary end point in all comparisons was the Beck Depression Inventory . Hypogonadal patients demonstrated significantly increased scores on the Beck inventory compared with eugonadal- , age- , weight- , and disease status-matched subjects ( 15.5+/-1.1 vs. 10.6+/-1.4 mean + /- SEM , P = 0.02 ) . Among the combined hypogonadal and eugonadal subjects , a significant inverse correlation was seen between the Beck score and both free ( r = 0.41 , P total serum testosterone levels ( r = -0.43 , P Beck score and testosterone levels remained highly significant , controlling for weight , viral load , CD4 count , and antidepressant use ( P Beck score greater than 18 or less than or equal to 18 , serum total and free testosterone levels were significantly lower in the subjects with a Beck score greater than 18 , whereas there were no differences in weight , viral load , CD4 count , or Karnofsky status . End of study data were available in 39 patients who completed the r and omized , placebo-controlled study . Beck score decreased significantly only in the subjects receiving testosterone ( -5.8+/-1.3 , P 0.05 ) . In a regression analysis , the change in Beck score was related significantly to change in weight ( P depression score in association with hypogonadism in men with AIDS wasting , independent of weight , virologic status , and other disease factors . In such patients , administration of testosterone results in a significant improvement in depression inventory score . This effect may be a direct effect of testosterone or related to positive effects of testosterone on weight and /or other anthropometric indices . Additional studies are needed to assess the effects of testosterone on clinical depression indices in human immunodeficiency virus-infected patients", "BACKGROUND Field studies of illicit anabolic- and rogenic steroid users suggest that some develop manic or aggressive reactions to these drugs-a potential public health problem . However , controlled laboratory evaluations of these effects remain limited . METHODS In a r and omized , placebo-controlled , crossover trial , we administered testosterone cypionate for 6 weeks in doses rising to 600 mg/wk and placebo for 6 weeks , separated by 6 weeks of no treatment , to 56 men aged 20 to 50 years . Psychiatric outcome measures included the Young Mania Rating Scale ( YMRS ) , the Point Subtraction Aggression Paradigm ( a computerized provocation test of aggression ) , the Aggression Question naire of Buss and Perry , the Symptom Checklist-90-R , daily diaries of manic and depressive symptoms , and similar weekly diaries completed by a \" significant other \" who knew the participant well . RESULTS Testosterone treatment significantly increased manic scores on the YMRS ( P = .002 ) , manic scores on daily diaries ( P = .003 ) , visual analog ratings of liking the drug effect ( P = .008 ) , and aggressive responses on the Point Subtraction Aggression Paradigm ( P = .03 ) . Drug response was highly variable : of 50 participants who received 600 mg/wk of testosterone cypionate , 42 ( 84 % ) exhibited minimal psychiatric effects ( maximum YMRS score , mildly hypomanic ( YMRS score , 10 - 19 ) , and 2 ( 4 % ) became markedly hypomanic ( YMRS score , > or = 20 ) . The 8 \" responders \" and 42 \" nonresponders \" did not differ significantly on baseline demographic , psychological , laboratory , or physiological measures . CONCLUSIONS Testosterone administration , 600 mg/wk increased ratings of manic symptoms in normal men . This effect , however , was not uniform across individuals ; most showed little psychological change , whereas a few developed prominent effects . The mechanism of these variable reactions remains unclear", "Background Uncontrolled studies show fatigue , anorexia , depression , and mortality are associated with low testosterone in men with cancer . Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions . The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer , by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale ( FACIT-Fatigue ) at day 29 . Methods This is a r and omized , double-blinded placebo-controlled trial . Out patients with advanced cancer , bioavailable testosterone ( BT ) 3/10 on the Edmonton Symptom Assessment Scale were eligible . Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70–270 ng/dL. Results Sixteen placebo and 13 testosterone-treated subjects were evaluable . No statistically significant difference was found for FACIT-fatigue scores between arms ( −2 ± 12 for placebo , 4 ± 8 for testosterone , p = 0.11 ) . Sexual Desire Inventory score ( p = 0.054 ) and performance status ( p = 0.02 ) improved in the testosterone group . Fatigue subscale scores were significantly better ( p = 0.03 ) in those treated with testosterone by day 72 . Conclusions Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life . Larger studies of longer duration are warranted", "BACKGROUND A large proportion of men over 65 years of age have bioavailable testosterone levels below the reference range of young adult men . The impact of this on musculoskeletal health and the potential for improvement in function in this group with testosterone supplementation require investigation . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - -87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone ( two 2.5-mg patches per day ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex-hormone binding globulin [ SHBG ] , estradiol , and estrone ) , bone mineral density ( BMD ; femoral neck , Ward 's triangle , trochanter , lumbar spine , and total body ) , bone turnover markers , lower extremity muscle strength , percent body fat , lean body mass , hemoglobin , hematocrit , prostate symptoms , and prostate specific antigen ( PSA ) levels . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . In these men , bioavailable testosterone levels increased from 3.2 + /- 1.2 nmol/l ( SD ) to 5.6 + /- 3.5 nmol/l ( p estradiol levels in either group , estrone levels increased in the testosterone group ( 103 + /- 26 pmol/l to 117 + /- 33 pmol/l ; p femoral neck BMD , whereas the control group lost 1.6 % over 12 months ( p = .015 ) . No significant changes were seen in markers of bone turnover in either group . Improvements in muscle strength were seen in both groups at 12 months compared with baseline scores . Strength increased 38 % ( p = .017 ) in the testosterone group and 27 % in the control group ( p = .06 ) , with no statistical difference between the groups . In the testosterone group , body fat decreased from 26.3 + /- 5.8 % to 24.6 + /- 6.5 % ( p = .001 ) , and lean body mass increased from 56.2 + /- 5.3 kg to 57.2 + /- 5.1 kg ( p = .001 ) , whereas body mass did not change . Men receiving testosterone had an increase in PSA from 2.0 + /- 1.4 microg/l to 2.6 + /- 1.8 microg/l ( p = .04 ) , whereas men receiving placebo had an increase in PSA from 1.9 + /- 1.0 microg/l to 2.2 + /- 1.5 microg/l ( p = .09 ) . No significant differences between groups were seen in hemoglobin , hematocrit , symptoms or signs of benign prostate hyperplasia , or PSA levels . CONCLUSIONS Transdermal testosterone ( 5 mg/d ) prevented bone loss at the femoral neck , decreased body fat , and increased lean body mass in a group of healthy men over age 65 with low bioavailable testosterone levels . In addition , both testosterone and placebo groups demonstrated gains in lower extremity muscle strength , possibly due to the beneficial effects of vitamin D. Testosterone did result in a modest increase in PSA levels but result ed in no change in signs or symptoms of prostate hyperplasia", "Transbuccal administration of drugs provides an easy route of administration . To test the safety and efficacy of a novel testosterone ( T ) product , we performed a r and omized , double blind , placebo-controlled study in a parallel design . Men with serum T levels below 250 ng/dL were administered either an active buccal tablet containing 10 mg T ( n = 7 ) or a buccal placebo tablet ( n = 6 ) containing 3 mg pseudoephedrine HCl for taste matching . Men were studied while taking a st and ard T enanthate dose , after 6 weeks of a wash-out period , and after 8 weeks of therapy . The men were matched for age ( mean + /- SD , 41 + /- 16 vs. 47 + /- 16 ) and type of hypogonadism ( three primary testicular failures in each group , with the remainder having a central etiology ) . Acute pharmacokinetic testing showed peak serum hormone levels at 30 min , with a mean serum T concentration of 2688 + /- 147 ng/dL ( range , 1820 - 3770 ng/dL ) . Levels returned to baseline in 4 - 6 h , result ing in a total T area under the curve level of 3865 ng/hn.dL , less than that using other available forms of T administration . Similar pharmacokinetics were observed for the hormone 's metabolites , bioavailable T , free T , and estradiol . After 8 weeks of treatment , the results of nocturnal penile tumescence studies evaluating rigidity and circumference were significantly different from those in the placebo group ( P therapy . In conclusion , transbuccal T therapy was sufficient to maintain normal sexual function while minimizing the total time of exposure to elevated circulating serum T levels", "Long-term glucocorticoid therapy in men is associated with loss of bone and muscle mass as well as a decrease in serum testosterone . We tested the effect of two and rogens , testosterone and its minimally aromatizable analog n and rolone , on muscle mass ( dual x-ray absorptiometry ) , muscle strength ( knee flexion and extension by isokinetic dynamometry ) , bone mineral density ( BMD ) , and quality of life ( Qualeffo-41 question naire ) in 51 men on a mean daily prednisone dose of 12.6 + /- 2.2 mg . Men were r and omized , double blind , to testosterone ( 200 mg mixed esters ) , n and rolone decanoate ( 200 mg ) , or placebo given every fortnight by i m injection for 12 months . At 12 months , both and rogens increased muscle mass ( mean change from baseline + 3.5 % , + 5.8 % , and -0.9 % in testosterone , n and rolone , and placebo groups , respectively , P muscle strength ( P Lumbar spine BMD increased significantly only in men treated with testosterone ( 4.7 + /- 1.1 % , P hip or total body BMD . Testosterone , but not n and rolone or placebo , improved overall quality of life ( P and rogen therapy may have a role in ameliorating adverse effects of glucocorticoid therapy such as muscle and bone loss and aromatization is necessary for and rogen action on bone but not on muscle", "OBJECTIVES The effect of testosterone ( T ) on sexual function in men is well established . However , less is known about its effects on cognitive function . The aim of this study is to investigate the relationship between T levels and sex-typed cognitive abilities in both eugonadal and hypogonadal men . DESIGN A single-blind placebo-controlled design was employed in this study . METHODS Thirty healthy eugonadal men and seven hypogonadal men participated in the study . Eugonadal men were r and omised into one of two treatment regimens : ( 1 ) active group -- receiving 200 mg of T enanthate i.m . weekly for 8 weeks ( raising T levels into the supraphysiological range ) or ( 2 ) placebo group -- receiving 200 mg of sodium chloride i.m . weekly for 8 weeks . The hypogonadal group received the physiological replacement dose of 200 mg T enanthate i.m . bi-weekly for 8 weeks . All groups underwent a battery of neuropsychological tests and had circulating T measured at baseline , and at weeks 4 and 8 during treatment . RESULTS A significant time by group interaction effect was found in the measure of spatial ability ( i.e. , block design test ) indicating that the active group 's performance declined significantly at week 4 , compared to placebo group ( F(4,64)=3.78 , P measure of verbal fluency ( i.e. , the Controlled Oral Word Association Test ) at week 4 ( F(4,64)=2.54 , P hypogonadal group performed less well than the eugonadal groups on all tests . CONCLUSIONS These results offer support to the notion that increased T has a differential effect on cognitive function , inhibiting spatial abilities while improving verbal fluency in eugonadal men", "Objective : To determine the efficacy of testosterone ( T ) supplementation on cognition in a sample of men with Alzheimer disease ( AD ) or mild cognitive impairment ( MCI ) . Methods : Fifteen patients with AD and 17 patients with MCI aged 63 to 85 years completed a r and omized , double-blind , placebo-controlled study . Nineteen participants received weekly intramuscular ( IM ) injections of 100 mg T enanthate and 13 participants received weekly injections of placebo ( saline ) for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , week 3 , and week 6 of treatment and again after 6 weeks of washout . Results : Peak serum total T levels were raised from baseline an average of 295 % in the active treatment group . Improvements in spatial memory ( p constructional abilities ( p verbal memory were evident in the T group . No changes were noted for selective and divided attention or language . Prostate specific antigen did not significantly change during this brief treatment . Conclusion : Testosterone supplementation may benefit selective cognitive functions in men with Alzheimer disease and mild cognitive impairment", "Although weight loss associated with human immunodeficiency virus ( HIV ) infection is multifactorial in its pathogenesis , it has been speculated that hypogonadism , a common occurrence in HIV disease , contributes to depletion of lean tissue and muscle dysfunction . We , therefore , examined the effects of testosterone replacement by means of And roderm , a permeation-enhanced , nongenital transdermal system , on lean body mass , body weight , muscle strength , health-related quality of life , and HIV-disease markers . We r and omly assigned 41 HIV-infected , ambulatory men , 18 - 60 yr of age , with serum testosterone levels below 400 ng/dL , to 1 of 2 treatment groups : group I , two placebo patches ( n = 21 ) ; or group II , two testosterone patches design ed to release 5 mg testosterone over 24 h. Eighteen men in the placebo group and 14 men in the testosterone group completed the 12-week treatment . Serum total and free testosterone and dihydrotestosterone levels increased , and LH and FSH levels decreased in the testosterone-treated , but not in the placebo-treated , men . Lean body mass and fat-free mass , measured by dual energy x-ray absorptiometry , increased significantly in men receiving testosterone patches [ change in lean body mass , + 1.345 + /- 0.533 kg ( P = 0.02 compared to no change ) ; change in fat-free mass , + 1.364 + /- 0.525 kg ( P = 0.02 compared to no change ) ] , but did not change in the placebo group [ change in lean body mass , 0.189 + /- 0.470 kg ( P = NS compared to no change ) ; change in fat-free mass , 0.186 + /- 0.470 kg ( P = NS compared to no change ) ] . However , there was no significant difference between the 2 treatment groups in the change in lean body mass . The change in lean body mass during treatment was moderately correlated with the increment in serum testosterone levels ( r = 0.41 ; P = 0.02 ) . The testosterone-treated men experienced a greater decrease in fat mass than those receiving placebo patches ( P = 0.04 ) . There was no significant change in body weight in either treatment group . Changes in overall quality of life scores did not correlate with testosterone treatment ; however , in the subcategory of role limitation due to emotional problems , the men in the testosterone group improved an average of 43 points of a 0 - 100 possible score , whereas those in the placebo group did not change . Red cell count increased in the testosterone group ( change in red cell count , + 0.1 + /- 0.1 10(12)/L ) but decreased in the placebo group ( change in red cell count , -0.2 + /- 0.1 10(12)/L ) . CD4 + and CD8 + T cell counts and plasma HIV copy number did not significantly change during treatment . Serum prostate-specific antigen and plasma lipid levels did not change in either treatment group . Testosterone replacement in HIV-infected men with low testosterone levels is safe and is associated with a 1.35-kg gain in lean body mass , a significantly greater reduction in fat mass than that achieved with placebo treatment , an increased red cell count , and an improvement in role limitation due to emotional problems . Further studies are needed to assess whether testosterone supplementation can produce clinical ly meaningful changes in muscle function and disease outcome in HIV-infected men", "The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels . Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors . Tau protein deposition is also affected by and rogen supplementation in animals . We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition , in particular the visual-spatial domain . Thirty-six male patients with a new diagnosis of Alzheimer 's disease had their total and bioavailable testosterone levels measured . None of the patients had been on acetylcholinesterase inhibitors . Ten of the 36 patients ( 28 % ) were deemed biochemically hypogonadal ( total testosterone testosterone and five to placebo . Initial Alzheimer 's Disease Assessment Scale cognitive subscale ( ADAScog ) and Mini Mental Status Examination ( MMSE ) ranged from 31 to 19 and from 17 to 22 , respectively . The clock drawing test ( CDT ) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities . Normal prostate-specific antigen ( PSA ) levels were essential before treatment with intramuscular testosterone , 200 mg every 2 weeks . Measurement of testosterone , complete blood count , lipids , PSA and neuropsychological cognitive tests were repeated at 3 , 6 , 9 and 12 months of treatment . In the testosterone-treated group , levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l ( p = 0.11 ) . Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l ( p = 0.10 ) . PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml ( p = 0.07 ) . ADAScog improved from a mean of 25 to 16.3 ( p = 0.02 ) ; MMSE improved from a mean of 19.4 to 23.2 ( p = 0.02 ) , CDT also improved from 2.2 to 3.2 ( p = 0.07 ) . One patient stopped treatment because of hypersexual behavior . The placebo-treated group deteriorated gradually . This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition , including visual-spatial skills in mild to moderate Alzheimer 's disease", "A r and omised double blind study was carried out with 50 men who had ST segment depression of 0.1 mV or more after a modified two-step exercise test . Rate and duration of exercise were the same for the last of each subject 's several pretreatment tests as for his tests after 4 and 8 weeks of treatment with placebo or testosterone cypionate , 200 mg , intramuscularly weekly . The sum of ST segment depression in leads II , V4 , V5 , and V6 taken immediately , and 2 , 4 , and 6 minutes after exercise did not change significantly after 4 or 8 weeks of placebo treatment , but did decrease by 32 per cent ( P less than 0.0001 ) and 51 per cent ( P less than 0.0001 ) after 4 and 8 weeks , respectively , of testosterone cypionate treatment . The mechanism by which testosterone cypionate treatment results in lessened postexercise ST segment depression is not established", "In the last ten years , numerous mechanisms by which sex steroids modify cortical function have been described . For example , estrogen replacement improves verbal memory in women , and animal studies have shown effects of estrogen on hippocampal synaptogenesis and function . Little is known about sex steroid effects on other aspects of memory , such as frontal lobe-mediated working memory . We examined the relationships between working memory and sex steroid concentrations and whether sex steroid supplementation would modify age-related loss of working memory in older men and women . Before hormone supplementation , working memory , tested with the Subject Ordered Pointing Test ( SOP ) , was worse in older subjects than younger subjects , and there was no evidence of gender differences at either age . Testosterone supplementation improved working memory in older men , but a similar enhancement of working memory was not found in older women supplemented with estrogen . In men , testosterone and estrogen effects were reciprocalwith better working memory related to a higher testosterone to estrogen ratio . These results suggest that sex steroids can modulate working memory in men and can act as modulators of cognition throughout life", "As men age , their serum testosterone concentrations decrease , as do their bone densities . Because bone density is also low in hypogonadal men , we hypothesized that increasing the serum testosterone concentrations of men over 65 yr to those found in young men would increase their bone densities . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch double blindly for 36 months . We measured bone mineral density by dual energy x-ray absorptiometry before and during treatment . Ninety-six men completed the entire 36-month protocol . The mean serum testosterone concentration in the men treated with testosterone increased from 367 + /- 79 ng/dL ( + /-SD ; 12.7 + /- 2.7 nmol/L ) before treatment to 625 + /- 249 ng/dL ( 21.7 + /- 8.6 nmol/L ; P mean bone mineral density of the lumbar spine increased ( P placebo-treated ( 2.5 + /- 0.6 % ) and testosterone-treated ( 4.2 + /- 0.8 % ) groups , but the mean changes did not differ between the groups . Linear regression analysis , however , demonstrated that the lower the pretreatment serum testosterone concentration , the greater the effect of testosterone treatment on lumbar spine bone density from 0 - 36 months ( P = 0.02 ) . This analysis showed a minimal effect ( 0.9 + /- 1.0 % ) of testosterone treatment on bone mineral density for a pretreatment serum testosterone concentration of 400 ng/dL ( 13.9 nmol/L ) , but an increase of 5.9 + /- 2.2 % for a pretreatment testosterone concentration of 200 ng/dL ( 6.9 nmol/L ) . Increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men did not increase lumbar spine bone density overall , but did increase it in those men with low pretreatment serum testosterone concentrations", "CONTEXT Recent clinical trials of i m testosterone in eugonadal men suggest positive effects on verbal memory , but other studies find no effect . OBJECTIVE Our objective was to determine whether supraphysiological testosterone influences verbal memory and brain function during a verbal memory task in healthy eugonadal older men . PATIENTS , DESIGN , AND SETTING Fifteen cognitively normal men , aged 66 - 86 yr , participated in a r and omized , double-blind , placebo-controlled crossover trial involving 9 months of participation per participant at a hospital-based research facility . INTERVENTION We used testosterone enanthate ( 200 mg i m every other week for 90 d ) crossed over with placebo ( sesame oil vehicle i m ) with a 90-d washout between treatments . MAIN OUTCOME MEASURES Performance was assessed on a st and ardized verbal memory test , and brain activity ( relative glucose metabolic rates ) in medial temporal and frontal regions was measured with positron emission tomography during a verbal memory task . RESULTS Treatment increased total testosterone by 241 % . Behavioral results showed a significant decrease in short-delay verbal memory with treatment ( P composite verbal memory measure ( P = 0.09 , effect size = 0.48 sd ) . Positron emission tomography scans revealed decreased relative activity in ventromedial temporal cortex ( i.e. right amygdala/entorhinal cortex ) and increased relative activity in bilateral prefrontal cortex with treatment . CONCLUSIONS Decreased verbal memory and altered relative activity in medial temporal and prefrontal regions suggest possible detrimental effects of supraphysiological testosterone supplementation in elderly men . The results do not rule out potential benefits with other regimens , cognitive tests , or population", "Background Experimental studies suggest that and rogens induce coronary vasodilatation . We performed this pilot project to examine the clinical effects of long-term low-dose and rogens in men with angina . Methods and Results Forty-six men with stable angina completed a 2-week , single-blind placebo run-in , followed by double-blind r and omization to 5 mg testosterone daily by transdermal patch or matching placebo for 12 weeks , in addition to their current medication . Time to 1-mm ST-segment depression on treadmill exercise testing and hormone levels were measured and quality of life was assessed by SF-36 at baseline and after 4 and 12 weeks of treatment . Active treatment result ed in a 2-fold increase in and rogen levels and an increase in time to 1-mm ST-segment depression from ( mean±SEM ) 309±27 seconds at baseline to 343±26 seconds after 4 weeks and to 361±22 seconds after 12 weeks . This change was statistically significant compared with that seen in the placebo group ( from 266±25 seconds at baseline to 284±23 seconds after 4 weeks and to 292±24 seconds after 12 weeks;P = 0.02 between the 2 groups by ANCOVA ) . The magnitude of the response was greater in those with lower baseline levels of bioavailable testosterone ( r = −0.455 , P changes in prostate specific antigen , hemoglobin , lipids , or coagulation profiles during the study . There were significant improvements in pain perception ( P = 0.026 ) and role limitation result ing from physical problems ( P = 0.024 ) in the testosterone-treated group . Conclusions Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia ", "BACKGROUND Many men older than 50 years have bioavailable testosterone levels below the reference range for young adult men . The impact of the decreased and rogen levels on cognition and health perception has received little attention . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - 87 ) with bioavailable testosterone levels below 128 ng/dl ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone ( 2 - 2.5 mg patches/d ) or placebo patches for 1 year . All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones [ testosterone , bioavailable testosterone , sex hormone binding globulin ( SHBG ) , estradiol , and estrone ] , cognitive tests ( Digit Symbol , Digit Span , Trailmaking A and B ) , health perception ( Medical Outcome Survey Short-form 36 or SF-36 ) , lower extremity muscle strength and power , and calcium intake . RESULTS Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . Bioavailable testosterone levels increased from 93 + /- 34 ( SD ) to 162 + /- 100 ng/dl ( p estradiol levels in either group , estrone levels increased in the testosterone group ( 28 + /- 7 to 32 + /- 9 pg/dl , p = .017 ) . Scores on the Digit Symbol test improved in both the testosterone and placebo groups . Scores on Trailmaking B improved in men treated with testosterone ( p Trailmaking B for the entire group were correlated with 12-month testosterone levels ( p = .016 ) . Scores for health perception measured by SF-36 did not change significantly , though scores of mental and general health declined in both groups during the 12-month intervention . Twelve-month bioavailable testosterone scores were directly correlated with scores for physical role ( p = .022 ) , vitality ( p = .036 ) , and the physical composite score ( p = .010 ) . CONCLUSIONS Transdermal testosterone treatment in men with low bioavailable testosterone levels does not impair and may improve cognitive function . Treatment did not improve health perception but this may have been due to the side effects of skin irritation suggested by similar reactions in both the testosterone and placebo groups", "BACKGROUND Our laboratory has previously reported that testosterone ( T ) administration to older men significantly improves cognitive function . This study examined potential changes in insulin-like growth factor ( IGF ) IGF-I , IGF-II and IGF-related binding proteins in response to T administration in older men and their relationship to cognitive functioning . METHODS Twenty-five healthy community dwelling volunteers , ranging in age from 50 - 80 years were r and omized to receive weekly intra-muscular ( i.m . ) injections of either 100 mg T enanthate or placebo ( saline ) for 6 weeks . Serum hormone levels and cognitive functioning was assessed at baseline and twice during treatment . RESULTS Significant positive associations between IGF-I and IGF-II and spatial memory , spatial reasoning , and verbal fluency were observed after 6 weeks of T administration . Increased serum T levels from treatment were positively associated with improvement in spatial reasoning performance , whereas estradiol was associated with a decline in divided attention performance . Serum IGF-I , IGF-II and IGFBPs did not change in response to T treatment . CONCLUSIONS Our results suggest that T , estradiol and IGF-I may have independent and selective effects on cognitive functioning . Positive associations between T levels and cognition are consistent with an effect of and rogen treatment , whereas positive associations between IGF-I levels and cognition are reflective of a relationship between endogenous IGF-I levels and cognition", "Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease ( COPD ) . Men with COPD have high prevalence of low testosterone levels , which may contribute to muscle weakness . We determined effects of testosterone supplementation ( 100 mg of testosterone enanthate injected weekly ) with or without resistance training ( 45 minutes three times weekly ) on body composition and muscle function in 47 men with COPD ( mean FEV(1 ) = 40 % predicted ) and low testosterone levels ( mean = 320 ng/dl ) . Subjects were r and omized to 10 weeks of placebo injections + no training , testosterone injections + no training , placebo injections + resistance training , or testosterone injections + resistance training . Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration ( to the middle of the normal range for young men ) . The lean body mass ( by dual-energy X-ray absorptiometry ) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training ( p Increase in one-repetition maximum leg press strength averaged 17.2 % with testosterone alone , 17.4 % with resistance training alone , and 26.8 % with testosterone + resistance training ( p tolerated with no abnormalities in safety measures . Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels", "BACKGROUND Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease . The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown . OBJECTIVE The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity . METHODS IN this multicenter , r and omized , placebo-controlled , double-blind trial , 88 HIV-positive men with abdominal obesity ( waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm ) and total testosterone 125 - 400 ng/dl , or bioavailable testosterone less than 115 ng/dl , or free testosterone less than 50 pg/ml on stable antiretroviral regimen , and HIV RNA less than 10,000 copies per milliliter were r and omized to receive 10 g testosterone gel or placebo daily for 24 wk . Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0 , 12 , and 24 . We used an intention-to-treat approach and nonparametric statistical methods . RESULTS Baseline characteristics were balanced between groups . In 75 subjects evaluated , median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups ( testosterone 0.3 % , placebo 3.1 % , P = 0.75 ) . Total ( testosterone -1.5 % , placebo 4.3 % , P = 0.04 ) and sc ( testosterone-7.2 % , placebo 8.1 % , P abdominal fat mass decreased in testosterone-treated men , but increased in placebo group . Testosterone therapy was associated with significant decrease in whole body , trunk , and appendicular fat mass by dual energy x-ray absorptiometry ( all P whole body and trunk fat increased significantly in the placebo group . The percent of individuals reporting a decrease in abdomen ( P = 0.01 ) , neck ( P = 0.08 ) , and breast size ( P = 0.01 ) at wk 24 was significantly greater in testosterone-treated than placebo-treated men . Testosterone-treated men had greater increase in lean body mass than placebo ( testosterone 1.3 % , placebo -0.3 , P = 0.02 ) . Plasma insulin , fasting glucose , and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly . Testosterone therapy was well tolerated . CONCLUSIONS Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body , total , and sc abdominal fat mass and a greater increase in lean mass compared to placebo . However , changes in visceral fat mass were not significantly different between groups . Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk", "BACKGROUND Sex hormones are known to affect cholesterol levels and vascular tone in women . The effects of testosterone on cholesterol and vascular tone in men are less well understood . Low testosterone levels have been associated with higher cholesterol levels in epidemiologic studies , but testosterone replacement has result ed in variable changes in cholesterol levels . Similarly , clinical studies suggest that testosterone may be vasodilatory , but few studies have directly evaluated the effects of testosterone on vascular tone . METHODS Sixty-seven men ( mean age 76 + /- 4 years , range 65 - 87 ) with bioavailable testosterone levels below 4.44 nmol/l ( lower limit for adult normal range ) were r and omized to receive transdermal testosterone ( 2 - 2.5 mg patches/d ) or placebo patches for 1 year . Twenty-three men ( 34 % ) withdrew from the study ; 44 men completed the trial . RESULTS While total cholesterol , triglyceride , and low-density lipoprotein cholesterol levels did not significantly change during the year of therapy , high-density lipoprotein ( HDL ) levels ( p = .004 ) and , specifically , HDL(2 ) subfraction ( p = .02 ) decreased in men receiving testosterone supplementation . Vascular tone was measured by brachial artery reactivity in 36 men . Endothelium-dependent brachial artery reactivity did not change from baseline measurements in men receiving transdermal testosterone ( 0.3 + /- 6.7 % to 1.6 + /- 4.6 % ; p = .58 ) or in the placebo group ( 3.2 + /- 5.5 % to 0.7 + /- 5.5 % ; p = .23 ) . CONCLUSIONS Transdermal testosterone decreased HDL(2 ) cholesterol but did not affect vascular reactivity in men older than 65 years selected for low testosterone levels . No study to date has addressed the direct relationship between testosterone replacement and cardiovascular events", "Testosterone ( T ) therapy in older men with low serum T levels increases lean body mass and decreases fat mass . These changes might improve physical performance and strength ; however , it has not been established whether T therapy improves functional outcome in older men . Moreover , concerns exist about the impact of T therapy on the prostate in older men . The administration of finasteride ( F ) , which partially blocks the conversion of T to the more potent and rogen , dihydrotestosterone , attenuates the impact of T replacement on prostate size and prostate-specific antigen . We hypothesized that T replacement in older , hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance , strength , and body composition . Seventy men with low serum T ( , were r and omly assigned to receive one of three regimens for 36 months : 1 ) T enanthate , 200 mg i m every 2 wk , with placebo pills daily ( T-only ) ; 2 ) T enanthate , 200 mg every 2 wk , with 5 mg F daily ( T + F ) ; or 3 ) placebo injections and pills ( placebo ) . We obtained serial measurements of timed physical performance , grip strength , lower extremity strength , body composition ( by dual-energy x-ray absorptiometry ) , fasting cholesterol profiles , and hormones . Fifty men completed the 36-month protocol . After 36 months , T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [ 4.3 + /- 1.6 % ( mean + /- sem , T-only ) and 3.8 + /- 1.0 % ( T + F ) vs. -5.6 + /- 1.9 % for placebo ( P h and grip strength compared with baseline and placebo ( P lean body mass [ 3.77 + /- 0.55 kg ( T-only ) and 3.64 + /- 0.56 kg ( T + F ) vs. -0.21 + /- 0.55 kg for placebo ( P decreased fat mass , and significantly decreased total cholesterol , low-density lipoprotein , and leptin , without affecting high-density lipoprotein , adiponectin , or fasting insulin levels . These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months , when administered alone or when combined with F , and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men", "BACKGROUND The relevance of the age-associated decline in testosterone for cognition in elderly men is still poorly understood . One hypothesis is that testosterone enhances spatial abilities , while it might impair verbal skills . METHODS Thirty elderly men received a single testosterone ( 250 mg testosterone enanthate ) or placebo injection . Cognitive performance was tested before and 5 days after treatment using spatial as well as verbal tests . RESULTS Five days after injection , testosterone and estradiol levels were still in the supraphysiologic range . In the verbal fluency task , the placebo group , but not the testosterone group , showed a practice effect . Therefore , the testosterone group performed significantly worse than the placebo group after treatment . No effects of testosterone were observed in the other verbal and spatial tasks . CONCLUSIONS The present finding , that testosterone blocks the practice effect in verbal fluency , partly supports the general idea that sex steroids modulate performance in tests with known gender differences . Moreover it demonstrates that these effects can occur rapidly . However , beneficial effects on spatial cognition or memory might need more time to develop and /or might only occur when a less pronounced testosterone increase is induced", "Testosterone ( T ) levels decline as men age , but it is unclear whether this has an effect on cognition . Some studies indicate that lower T levels are associated with memory loss ; thus , maintaining a higher T level could have positive effects on aspects of cognitive function . Concerns exist , however , about the effect of T therapy on the prostate in older men . We hypothesized that T replacement in older men with low T levels would improve aspects of cognitive function and that the addition of finasteride would not affect the T-induced cognitive improvements . Healthy men , 65 to 83 years of age , with baseline total T below 350 ng/dL and no evidence of cognitive impairment were r and omly assigned to 1 of 3 regimens : 200 mg of T every 2 weeks by intramuscular injection with placebo pill daily ( T-only ) , 200 mg of T every 2 weeks by intramuscular injection with 5 mg of finasteride daily ( T+F ) , or placebo injections and pills ( placebo ) . Sixty-nine men completed baseline cognitive testing ; 65 completed at least 4 months , and 46 completed all 36 months of the study . Participants were given a battery of cognitive evaluations at baseline , 4 months , and 36 months , along with measurement of serum hormone levels . Serum total T , bioavailable T , and estradiol levels in the T-only and T+F groups significantly increased throughout the treatment period , whereas these hormone levels did not change in the placebo group . Only minimally significant differences were seen among the 3 groups in any evaluation of cognitive performance , either in the short-term ( 4 months ) or the long-term ( 36 months ) analysis . These results indicate that T replacement , whether given alone or in combination with finasteride , for 36 months in healthy older men without cognitive impairment at baseline has no clinical ly significant effect on tests of cognitive function . Further studies are warranted to determine whether hormone replacement in men with preexisting cognitive impairment is beneficial", "IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown . A recent r and omized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety . OBJECTIVES To assess the association between testosterone therapy and all-cause mortality , myocardial infa rct ion ( MI ) , or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease . DESIGN , SETTING , AND PATIENTS A retrospective national cohort study of men with low testosterone levels ( coronary angiography in the Veterans Affairs ( VA ) system between 2005 and 2011 . MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality , MI , and ischemic stroke . RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL , 1223 patients started testosterone therapy after a median of 531 days following coronary angiography . Of the 1710 outcome events , 748 men died , 443 had MIs , and 519 had strokes . Of 7486 patients not receiving testosterone therapy , 681 died , 420 had MIs , and 486 had strokes . Among 1223 patients receiving testosterone therapy , 67 died , 23 had MIs , and 33 had strokes . At 3 years after coronary angiography , the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group , with an absolute risk difference of 5.8%(95%CI , -1.4%to 13.1 % ) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1 % vs 11.3 % ; at 2 years , 15.4 % vs 18.5 % ; and at 3 years , 19.9 % vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease ( test for interaction , P = .41 ) . CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level , the use of testosterone therapy was associated with increased risk of adverse outcomes . These findings may inform the discussion about the potential risks of testosterone therapy", "OBJECTIVE In women , sex hormones cause increased morbidity and mortality in patients with coronary heart disease ( CHD ) and adversely affect the coagulation profile . We have studied the effect of physiological testosterone replacement therapy in men on coagulation factor expression , to determine if there is an increased risk of thrombosis . METHODS Double-blind , r and omized , placebo-controlled trial of testosterone in 46 men with chronic stable angina . Measurements of free , total and bioavailable testosterone , luteinising hormone ( LH ) and follicle-stimulating hormone ( FSH ) , estradiol , plasminogen activator inhibitor-1 ( PAI-1 ) , fibrinogen , tissue plasminogen activator ( tPA ) and full blood count were made at 0 , 6 and 14 weeks . RESULTS Bioavailable testosterone levels were : 2.58 + /- 0.58 nmol/l at baseline , compared with 3.35 + /- 0.31 nmol/l at week 14 ( P placebo group ( P was not significant ) . There was no change in fibrinogen ( 3.03 + /- 0.18 g/l at baseline and 3.02 + /- 0.18 g/l at week 14 , P = 0.24 ) , tPA activity ( 26.77 + /- 4.9 Iu/ml and 25.67 + /- 4.4 Iu/ml , P = 0.88 ) or PAI-1 activity ( 0.49 + /- 0.85 Iu/ml and 0.36 + /- 0.06 Iu/ml , P = 0.16 ) with active treatment and no differences between the groups ( at week 14 , P value 0.98 , 0.59 and 0.8 for fibrinogen , PAI-1 and tPA respectively ) . Haemoglobin concentration did not change over time , in the testosterone group ( 1.44 + /- 0.02 g/l and 1.45 + /- 0.02 g/l , P = 0.22 ) . CONCLUSION Physiological testosterone replacement does not adversely affect blood coagulation status", "BACKGROUND Testosterone supplementation has been shown to increase muscle mass and strength in healthy older men . The safety and efficacy of testosterone treatment in older men who have limitations in mobility have not been studied . METHODS Community-dwelling men , 65 years of age or older , with limitations in mobility and a total serum testosterone level of 100 to 350 ng per deciliter ( 3.5 to 12.1 nmol per liter ) or a free serum testosterone level of less than 50 pg per milliliter ( 173 pmol per liter ) were r and omly assigned to receive placebo gel or testosterone gel , to be applied daily for 6 months . Adverse events were categorized with the use of the Medical Dictionary for Regulatory Activities classification . The data and safety monitoring board recommended that the trial be discontinued early because there was a significantly higher rate of adverse cardiovascular events in the testosterone group than in the placebo group . RESULTS A total of 209 men ( mean age , 74 years ) were enrolled at the time the trial was terminated . At baseline , there was a high prevalence of hypertension , diabetes , hyperlipidemia , and obesity among the participants . During the course of the study , the testosterone group had higher rates of cardiac , respiratory , and dermatologic events than did the placebo group . A total of 23 subjects in the testosterone group , as compared with 5 in the placebo group , had cardiovascular-related adverse events . The relative risk of a cardiovascular-related adverse event remained constant throughout the 6-month treatment period . As compared with the placebo group , the testosterone group had significantly greater improvements in leg-press and chest-press strength and in stair climbing while carrying a load . CONCLUSIONS In this population of older men with limitations in mobility and a high prevalence of chronic disease , the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events . The small size of the trial and the unique population prevent broader inferences from being made about the safety of testosterone therapy . ( Clinical Trials.gov number , NCT00240981 .", "AIMS Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism , vasodilator incapacity , and loss of skeletal muscle bulk and function . In men , and rogens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties . METHODS AND RESULTS We conducted a r and omized , double-blind , placebo-controlled parallel trial of testosterone replacement therapy ( 5 mg And roderm ) at physiological doses in 76 men ( mean+/-SD , age 64+/-9.9 ) with heart failure ( ejection fraction 32.5+/-11 % ) over a maximum follow-up period of 12 months . The primary endpoint was functional capacity as assessed by the incremental shuttle walk test ( ISWT ) . At baseline , 18 ( 24 % ) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT ( r=0.3 , P=0.01 ) . Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period ( mean change + 25+/-15 m ) corresponding to a 15+/-11 % improvement from baseline ( P=0.006 ANOVA ) . Symptoms improved by at least one functional class on testosterone in 13 ( 35 % ) vs. 3 ( 8 % ) on placebo ( P=0.01 ) . No significant changes were found in h and grip strength , skeletal muscle bulk by cross-sectional computed tomography , or in tumour necrosis factor levels . Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients . CONCLUSION Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure", "OBJECTIVE Low levels of testosterone in men have been shown to be associated with type 2 diabetes , visceral adiposity , dyslipidaemia and metabolic syndrome . We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes . DESIGN This was a double-blind placebo-controlled crossover study in 24 hypogonadal men ( 10 treated with insulin ) over the age of 30 years with type 2 diabetes . METHODS Patients were treated with i.m . testosterone 200 mg every 2 weeks or placebo for 3 months in r and om order , followed by a washout period of 1 month before the alternate treatment phase . The primary outcomes were changes in fasting insulin sensitivity ( as measured by homeostatic model index ( HOMA ) in those not on insulin ) , fasting blood glucose and glycated haemoglobin . The secondary outcomes were changes in body composition , fasting lipids and blood pressure . Statistical analysis was performed on the delta values , with the treatment effect of placebo compared against the treatment effect of testosterone . RESULTS Testosterone therapy reduced the HOMA index ( -1.73 + /- 0.67 , P = 0.02 , n = 14 ) , indicating an improved fasting insulin sensitivity . Glycated haemoglobin was also reduced ( -0.37 + /- 0.17 % , P = 0.03 ) , as was the fasting blood glucose ( -1.58 + /- 0.68 mmol/l , P = 0.03 ) . Testosterone treatment result ed in a reduction in visceral adiposity as assessed by waist circumference ( -1.63 + /- 0.71 cm , P = 0.03 ) and waist/hip ratio ( -0.03 + /- 0.01 , P = 0.01 ) . Total cholesterol decreased with testosterone therapy ( -0.4 + /- 0.17 mmol/l , P = 0.03 ) but no effect on blood pressure was observed . CONCLUSIONS Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes . Improvements in glycaemic control , insulin resistance , cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk", "Abstract Purpose : We aim ed to compare therapeutic effects of intramuscular ( IM ) n and rolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome ( AWS ) with placebo control . Methods : In this r and omized , double-blind , placebo-controlled , 12-week trial , 104 patients with AWS who satisfied our inclusion criteria were r and omly allotted in a 2:2:1 ratio to the 3 intervention groups : n and rolone , testosterone , and placebo . We administered 150 mg n and rolone and 250 mg testosterone ( both IM , biweekly ) . The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the n and rolone decanoate , testosterone , and placebo groups . Results : Intent-to-treat analysis was done . The n and rolone group recorded maximum mean increase in weight ( 3.20 kg ; post hoc P Body mass index ( BMI ) of subjects in the n and rolone group had a significantly greater increase ( mean = 1.28 ) compared to both testosterone ( post hoc P Waist circumference and triceps skinfold thickness of patients on n and rolone showed similar results . N and rolone also ensured a better quality of life . Patients with low testosterone level ( n and rolone therapy , which increased their weight and BMI significantly compared to placebo ( P n and rolone in male AWS patients , including the and rogen deficient", "BACKGROUND The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms ( diminished libido , depressed mood , low energy , and depleted muscle mass ) in men with symptomatic human immunodeficiency virus illness . METHODS Seventy-four patients were enrolled in a double-blind , placebo-controlled 6-week trial with bi-weekly testosterone injections , followed by 12 weeks of open-label maintenance treatment . Major outcome measures were Clinical Global Impressions Scale ratings for libido , mood , energy , and erectile function ; Hamilton Depression Rating Scale scores , and Chalder Fatigue Scale scores . Body composition changes were assessed with bioelectric impedance analysis . RESULTS Seventy men completed the 6-week trial . Response rates , defined as much or very much improved libido , were 74 % ( 28/38 ) for patients r and omized to testosterone , and 19 % ( 6/32 ) for placebo-treated patients ( P fatigue at baseline , 59 % ( 20/34 ) receiving testosterone and 25 % ( 7/28 ) receiving placebo reported improved energy ( P testosterone-treated patients reported improved mood compared with 14 % of placebo-treated patients ( Fisher exact test = .08 ) . With testosterone treatment , average increase in muscle mass over 12 weeks was 1.6 kg for the whole group , and 2.2 kg for the 14 men with wasting at baseline . Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks . CONCLUSION Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness , restoring libido and energy , alleviating depressed mood , and increasing muscle mass", "CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD", "BACKGROUND Athletes often take and rogenic steroids in an attempt to increase their strength . The efficacy of these substances for this purpose is unsubstantiated , however . METHODS We r and omly assigned 43 normal men to one of four groups : placebo with no exercise ; testosterone with no exercise ; placebo plus exercise ; and testosterone plus exercise . The men received injections of 600 mg of testosterone enanthate or placebo weekly for 10 weeks . The men in the exercise groups performed st and ardized weight-lifting exercises three times weekly . Before and after the treatment period , fat-free mass was determined by underwater weighing , muscle size was measured by magnetic resonance imaging , and the strength of the arms and legs was assessed by bench-press and squatting exercises , respectively . RESULTS Among the men in the no-exercise groups , those given testosterone had greater increases than those given placebo in muscle size in their arms ( mean [ + /-SE ] change in triceps area , 424 + /- 104 vs. -81 + /- 109 square millimeters ; P legs ( change in quadriceps area , 607 + /- 123 vs. -131 + /- 111 square millimeters ; P increases in strength in the bench-press ( 9 + /- 4 vs. -1 + /- 1 kg , P squatting exercises ( 16 + /- 4 vs. 3 + /- 1 kg , P exercise had greater increases in fat-free mass ( 6.1 + /- 0.6 kg ) and muscle size ( triceps area , 501 + /- 104 square millimeters ; quadriceps area , 1174 + /- 91 square millimeters ) than those assigned to either no-exercise group , and greater increases in muscle strength ( bench-press strength , 22 + /- 2 kg ; squatting-exercise capacity , 38 + /- 4 kg ) than either no-exercise group . Neither mood nor behavior was altered in any group . CONCLUSIONS Supraphysiologic doses of testosterone , especially when combined with strength training , increase fat-free mass and muscle size and strength in normal men", "OBJECTIVES To To compare testosterone undecanoate versus propionyl-L-carnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms . METHODS A total of 120 patients were r and omized into three groups . The mean patient age was 66 years ( range 60 to 74 ) . Group 1 was given testosterone undecanoate 160 mg/day , the second group was given propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day . The third group was given a placebo ( starch ) . Drugs and placebo were given for 6 months . The assessed variables were total prostate-specific antigen , prostate volume , peak systolic velocity , end-diastolic velocity , resistive index of cavernosal penile arteries , nocturnal penile tumescence , total and free testosterone , prolactin , luteinizing hormone , International Index of Erectile Function score , Depression Melancholia Scale score , fatigue scale score , and incidence of side effects . The assessment was performed at intervals before , during , and after therapy . RESULTS Testosterone and carnitines significantly improved the peak systolic velocity , end-diastolic velocity , resistive index , nocturnal penile tumescence , International Index of Erectile Function score , Depression Melancholia Scale score , and fatigue scale score . Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score . Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone ; carnitines did not . No drug significantly modified prostate-specific antigen or prolactin . Carnitines and testosterone proved effective for as long as they were administered , with suspension provoking a reversal to baseline values . Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension . Placebo administration proved ineffective . Negligible side effects emerged . CONCLUSIONS Testosterone and , especially , carnitines proved to be active drugs for the therapy of symptoms associated with male aging", "objectives We have recently shown that , in men with erectile dysfunction ( ED ) , free testosterone ( FT ) directly correlates with penile arterial inflow . This led us to further investigate the effect(s ) of and rogen administration on cavernous arteries in patients failing sildenafil treatment", "CONTEXT Declines in GH and testosterone ( Te ) secretion may contribute to the detrimental aging changes of elderly men . OBJECTIVE To assess the effects of near-physiological GH with/without Te administration on lean body mass , total body fat , midthigh muscle cross-section area , muscle strength , aerobic capacity , condition-specific quality of life ( Age-Related Hormone Deficiency-Dependent Quality of Life question naire ) , and generic health status ( 36-Item Short-Form Health Survey ) of older men . DESIGN , SETTING S , AND PARTICIPANTS A 6-month , r and omized , double-blind , placebo-controlled trial was performed on 80 healthy , community-dwelling , older men ( age , 65 - 80 yr ) . INTERVENTIONS Participants were r and omized to receive 1 ) placebo GH or placebo Te , 2 ) recombinant human GH ( rhGH ) and placebo Te ( GH ) , 3 ) Te and placebo rhGH ( Te ) , or 4 ) rhGH and Te ( GHTe ) . GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range . A fixed dose of Te ( 5 mg ) was given by transdermal patches . RESULTS Lean body mass increased with GHTe ( P = 0.008 ) and GH ( P = 0.004 ) , compared with placebo . Total body fat decreased with GHTe only ( P = 0.02 ) . Midthigh muscle ( P = 0.006 ) and aerobic capacity ( P Muscle strength changes were variable ; one of six measures significantly increased with GHTe . Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life question naire score ( P = 0.007 ) in the GH and GHTe groups . Bodily pain increased with GH alone , as determined by the Short-Form Health Survey ( P = 0.003 ) . There were no major adverse effects . CONCLUSION Coadministration of low dose GH with Te result ed in beneficial changes being observed more often than with either GH or Te alone", "Serum testosterone levels decline significantly with aging and this has been associated with reduced sexual function . We have conducted a double-blind , r and omized , placebo-controlled trial to investigate the effect of testosterone supplementation on sexual function in 237 elderly men with a testosterone level Participants were r and omly assigned to receive oral testosterone undecanoate or a placebo for 6 months . A total of 207 men completed the study . After treatment , there were no differences in scores on sexual function between the groups . Sub analysis showed that although a baseline testosterone level in the lowest tertile was associated with significantly lower scores for sexual fantasies , desire of sexual contact and frequency of sexual contact , supplementation of testosterone did not result in improvement on any of these items in this group . In conclusion , the findings do not support the view that testosterone undecanoate supplementation for 6 months to elderly men with low-normal testosterone concentrations favorably affects sexual function ", "OBJECTIVE Hypogonadism and subthreshold depression are common conditions in elderly men . The objective of this study was to examine the effect of testosterone treatment in older , hypogonadal men with subthreshold depression . METHOD A r and omized , double-blind , placebo-controlled study was conducted at a university-affiliated Veterans Affairs Medical Center among men aged 50 years or older ( N = 33 ) with screening total testosterone levels of Recruitment for the study was conducted from November 2002 through May 2005 . Participants received either 7.5 g of testosterone gel or placebo gel daily for 12 weeks , followed by a 12-week open-label extension phase during which all subjects received 7.5 g of testosterone gel . The primary outcome measure was the change in the Hamilton Rating Scale for Depression ( HAM-D ) score from baseline to the end of the double-blind phase . Secondary outcome measures were remission of subthreshold depression ( defined a priori as a HAM-D score changes in the Hopkins Symptom Checklist depression scale , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the short-form 16-item Quality of Life Enjoyment and Satisfaction Question naire . RESULTS At the end of the double-blind phase , testosterone-treated men had a greater reduction in HAM-D scores ( p = .024 ) and a higher remission rate of subthreshold depression ( 52.9 % vs. 18.8 % , p = .041 ) than did placebo-treated men , but there were no differences in other secondary outcome measures between groups . At the end of the open-label phase , the testosterone group had sustained improvement , the control group improved , and there were no differences between groups in any outcome measures . CONCLUSION These results suggest that testosterone replacement may be efficacious treatment for subthreshold depression in older men with hypogonadism . Larger studies are needed to corroborate these findings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00202462", "BACKGROUND Symptoms of male hypogonadism include low libido , fatigue , and dysphoria and are alleviated with testosterone replacement . The prevalence of major depressive disorder ( MDD ) in hypogonadal men is not known , nor is the antidepressant efficacy of testosterone replacement in depressed , hypogonadal men . METHOD A 6-week double-blind , placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level , defined as total serum testosterone Patients were r and omly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate , 200 mg , or sesame seed oil ( placebo ) . The primary outcome measure was the 24-item Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Thirty patients were r and omly assigned to an intervention ; 13 received testosterone , and 17 received placebo . Mean + /- SD age was 52+/-10 years , mean testosterone level was 266.1+/-50.6 ng/dL , and mean baseline HAM-D score was 21+/-8 . All patients who received testosterone achieved normalization of their testosterone levels . The HAM-D scores decreased in both testosterone and placebo groups , and there were no significant between-group differences : reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo . Response rate , defined as a 50 % or greater reduction in HAM-D score , was 38.5 % ( 5/13 ) for patients who received testosterone and 41.2 % ( 7/17 ) for patients who received placebo . Patients receiving testosterone had a marginal but statistically significant improvement in sexual function ( p = .02 ) . CONCLUSION In this clinical trial with depressed , hypogonadal men , antidepressant effects of testosterone replacement could not be differentiated from those of placebo", "BACKGROUND AND METHODS In order to assess the effects of testosterone undecanoate ( TU ; 120 mg/d orally for 2 months ) on serum lipid , lipoprotein , and apolipoprotein levels in healthy elderly men , the placebo ( PL ) controlled study was performed on 37 elderly men , aged between 53 and 89 years . In all subjects venous blood sample s were taken after an overnight ( 10 hours ) fast and sera were stored -70 degrees C until analysis . RESULTS In PL group , neither hormonal data nor lipid , lipoprotein , and apolipoprotein levels showed significant changes . After TU supplementation , serum total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , and estradiol ( E2 ) levels decreased from 198 + /- 30.7 mg/dl to 174 + /- 41.9 mg/dl ( p serum triglyceride ( TG ) , high-density lipoprotein cholesterol ( HDL-C ) , and apolipoprotein ( apo ) A-1 and apo B levels after TU treatment . The mean ratios TC/HDL-C and LDL-C/HDL-C as coronary risk factor criteria decreased significantly in the TU but not in the PL group . No obvious side effect was observed in those who took TU except for reported pyrosis in 2 of 17 elderly men . CONCLUSIONS These data indicate that the increased serum levels of total testosterone ( TT ) produced by administration of TU , 120 mg/d orally for 2 months lead to suppressed levels of TC and LDL-C and E2 but not significantly changed levels of TC , HDL-C , apo A-1 and apo B. Thus , we conclude that TU may be an effective drug for protecting coronary heart disease in healthy elderly men with lowered TT and FT levels . It may also have beneficial effects for sexual function and behavior", "Testosterone plays a role in the organization of behavior during development . The authors examined whether testosterone could play a maintenance role in behavior as well . In a double-blind manner , verbal and visual memory , spatial cognition , motor speed , cognitive flexibility , and mood in a group of healthy older men who were supplemented for 3 months with testosterone were assessed . The increase in testosterone levels to 150 % of baseline levels result ed in a significant enhancement of spatial cognition , but no change in any other cognitive domain was found . Testosterone supplementation influenced the endogenous production of estradiol , and estradiol was found to have an inverse relationship to spatial cognitive performance . These results suggest that testosterone supplementation can modify spatial cognition in older men ; however , it is likely that this occurs through testosterone 's influence on estrogen", "The AIDS wasting syndrome is characterized by loss of lean body mass out of proportion to weight [ 1 , 2 ] . The few effective treatments that have been identified are short-term pharmacologic agonists . Because loss of lean body mass is associated with decreased survival in men with the AIDS wasting syndrome [ 3 ] , development of therapeutic strategies to increase lean body mass is of critical importance . Half of all men with AIDS are hypogonadal [ 4 ] , and serum and rogen levels correlate with lean body mass among hypogonadal men with the AIDS wasting syndrome [ 5 ] . Previous studies in non-HIV-infected hypogonadal men show that and rogen administration has a significant anabolic effect on body composition [ 6 - 10 ] . We hypothesized that loss of the potent anabolic hormone testosterone in men with the AIDS wasting syndrome may contribute to the critical loss of lean body mass . Therefore , we investigated the effects of physiologic testosterone administration in men with the AIDS wasting syndrome . Methods Patients In 1995 and 1996 , 51 HIV-positive men ( 42 8 years of age ) were recruited from the multidisciplinary HIV practice at the Massachusetts General Hospital and from newspaper , television , and radio advertisements . Weight , testosterone levels , and medication history were determined at a screening assessment . To be included in the study , patients had to have decreased free testosterone levels , defined as less than 42 pmol/L at screening ( normal range for men 18 to 49 years of age , 42 to 121 pmol/L [ 12.0 to 35.0 pg/mL ] ) , and wasting , defined as weight less than 90 % of ideal body weight or involuntary weight loss greater than 10 % of baseline weight [ 11 ] . The CD4 count was not an inclusion criterion . We excluded patients with severe diarrhea ( > 6 stools/d ) ; hemoglobin value less than 5.0 mmol/L ( 2 mg/dL ) ; new opportunistic infection within 6 weeks of screening ; use of testosterone , anabolic steroids , growth hormone , ketoconazole , or systemic steroid therapy within 3 months before screening ; or history of prostate cancer . In addition , patients receiving antiretroviral agents , including protease inhibitors , were required to be receiving a stable regimen for at least 6 weeks before study entry . Ten patients were receiving long-term , stable therapy with megestrol acetate for at least 8 weeks before study entry and were equally distributed between the two treatment groups ( 5 in the testosterone group and 5 in the placebo group ) . All patients gave written consent , and the study was approved by the Human Studies Committee of the Massachusetts General Hospital . Protocol Patients were r and omly assigned to receive testosterone enanthate , 300 mg ( Bio-Technology General Corp. , Iselin , New Jersey ) , or placebo intramuscularly every 3 weeks by self-injection . Participants were stratified for weight less than or greater than 90 % of ideal body weight and megestrol acetate use before r and omization . R and omization was performed by the Massachusetts General Hospital Pharmacy by using a permuted block algorithm . The correspondence between patient code number and drug was generated by the study statistician ; this list was available to the hospital pharmacist but not to the investigators or patients . The placebo contained sesame oil with chlorobutanol as a preservative and matched testosterone enanthate in color and consistency . The study drug was bottled by the Massachusetts General Hospital Pharmacy in containers labeled with the study name , expiration date , and patient code . Before the first injection , participants returned within approximately 2 weeks of the screening visit for a 3-day baseline inpatient visit to the General Clinical Research Center at the Massachusetts General Hospital for hormonal , nutritional , immune function , and body composition analysis , which included assessment by dual-energy x-ray absorptiometry , bioimpedance analysis , potassium-4040 K ) isotope analysis , and measurement of urinary creatinine excretion . No patient experienced the onset of a new opportunistic infection , other complication , or substantial weight change between the screening and baseline visits . Patients were instructed on the proper technique for intramuscular injection ; those who were unable to self-administer the study drug received injections every 3 weeks from the nursing staff of the General Clinical Research Center . Patients returned for an outpatient visit at 3 months for assessment of weight and determination of total-body potassium content and for a 3-day inpatient visit at 6 months ; this visit was identical to the baseline evaluation . Patients also reported on response to therapy at the 6-month visit . Baseline data from 26 patients have been reported elsewhere [ 5 ] . Subsequent study visits were timed to correspond to the midpoint between study drug injections . Study drug compliance was confirmed by history , medication diaries , outpatient injection records , empty vial counts , and serum testosterone levels . History of medication use was assessed at each visit . The change in fat-free mass assessed by dual-energy x-ray absorptiometry was the primary clinical end point ; changes in weight , muscle mass , total body potassium content , and quality of life were secondary end points . Body Composition Analysis Body composition was determined by four methods : 1 ) dual-energy x-ray absorptiometry to assess fat and fat-free mass ( Hologic-2000 densitometer , Hologic , Inc. , Waltham , Massachusetts ; precision error , 3 % for fat and 1.5 % for fat-free mass [ 12 ] , 2 ) 40 K isotope analysis to assess total-body potassium content in a whole-body counter with sodium iodide detectors fixed above and below the patient at the xiphoid level ( Canberra Nuclear , Meriden , Connecticut ; precision error creatinine excretion averaged over 3 days ( during which the patient received a meat-free diet ) multiplied by a constant of 18 kg of muscle per gram of urinary creatinine and indexed for height to determine the percentage of predicted muscle mass [ 13 , 14 ] , and 4 ) bioimpedance analysis to determine total-body water content ( Bioelectrical Impedance Analyzer Model BIA-101 , RJL Systems , Clinton Turnpike , Michigan ; correlation with deuterium oxide equivalent to R = 0.99 [ 15 ] ) . Lean body mass was derived from total-body potassium content by using the Equation of Forbes and Lewis of 68.1 mEq of potassium per kg of lean body mass [ 16 ] . Nutritional Assessment Weight was measured on the first day of each visit after an overnight fast . The percentage of ideal body weight was calculated on the basis of st and ard height and weight tables [ 17 ] . Patients were instructed on completion of a 4-day food record , which was analyzed for total calorie , fat , protein , and carbohydrate content ( Minnesota Nutrition Data Systems , version 8A/2.6 , Minneapolis , Minnesota ) by the Clinical Research Center dietitian . Patients received an isocaloric , meat-free , protein-substituted diet 3 days before and during the inpatient assessment s at baseline and at 6 months , during which creatinine excretion and nitrogen balance were measured . Total urinary nitrogen excretion was measured by the Kjeldal technique from consecutive 24-hour collection s averaged over 3 days . Nonurinary nitrogen losses were assumed to be constant at 4 g/d [ 13 , 18 , 19 ] . Nitrogen intake was derived from total protein intake divided by a constant of 6.25 g of protein per g of nitrogen [ 19 ] . Calorie and protein intake were monitored on a daily basis and were modified to match the reports in the outpatient food records immediately before these visits . Resting energy expenditure was measured by indirect calorimetry with a metabolic cart . Energy requirements were calculated by using the Harris-Benedict equation [ 20 ] . Patient Reports of Response to Therapy Each patient 's perceived well-being was assessed at the end of the study by using nine linear analogue-scale questions on the overall treatment effect , change in quality of life , personal appearance , weight , and appetite ( Table 1 ) [ 21 ] . A Karnofsky score was also determined at each visit . Table 1 . Assessment of Patient Response to Therapy * Exercise Functional Testing Exercise history was assessed by a st and ardized question naire adapted from the study by Kohl and coworkers [ 22 ] . Exercise functional status was determined at the baseline and final visits by the physical therapy department of the Massachusetts General Hospital by using the 6-minute walk test , the timed sit-to-st and test , and the timed get-up- and -go test [ 23 - 25 ] . The distance covered in 6 minutes , the number of times the patient was able to move from a sitting to st and ing position in 10 seconds , and the time to cover a distance of 3 meters after st and ing from a seated position was recorded for each patient . Biochemical and Immunologic Assays Hematocrit and serum levels of follicle-stimulating hormone , luteinizing hormone , sex hormone-binding globulin , and prolactin were measured at the baseline and final visits by using published methods [ 26 ] . Serum levels of total and free testosterone were measured by radioimmunoassay kit ( Diagnostics Products Corp. , Los Angeles , California ) with intra-assay coefficients of variation of 5 % to 12 % for total testosterone and 3.2 % to 4.3 % for free testosterone . CD4 cell counts were measured by flow cytometry ( Becton Dickinson Immunocytochemistry Systems , San Jose , California ) . Viral burden was determined by using the Amplicor HIV-1 monitor test ( Roche Molecular Systems , Branchburg , New Jersey ) . Statistical Analysis Sample size was based on the change in lean body mass in response to testosterone administration among adult men with acquired hypogonadism [ 8 ] . A change of 3.2 % 4.0 % was expected over 6 months . With 20 patients in each group , the study had an 80 % chance of seeing an effect of testosterone at a", "To investigate ( 1 ) the effects of exogenous testosterone ( T ) on self- and partner-reported aggression and mood and ( 2 ) the role of trait impulsivity in the T-aggression relationship . Thirty eugonadal men with partners were r and omized into two treatment groups to receive : ( 1 ) 200 mg i m T enanthate weekly for 8 weeks or ( 2 ) 200 mg i m sodium chloride weekly for 8 weeks . Eight hypogonadal men received 200 mg i m T enanthate biweekly for 8 weeks . All groups completed a battery of behavior measures at baseline ( Week 0 ) and at Weeks 4 and 8 . Cognitive and motor impulsivity were the only predictors of self-reported total aggression ( over and above age and T levels ) at Weeks 0 , 4 , and 8 . No significant changes in aggression or mood levels were found in the eugonadal-treated group . Significant reductions in negative mood ( tension , anger , and fatigue ) followed by an increase in vigor were found in response to T treatment in the hypogonadal group . These results demonstrate that inability to control one 's behavior when such control is required by a particular situation ( impulsivity ) was found to significantly predict levels of aggression over and above age and T level . These data do not support the hypothesis that supraphysiological levels of T ( within this range ) lead to an increase in self- and partner-reported aggression or mood disturbances . Instead , for the first time , this study has identified the high level of negative affect experienced by hypogonadal patients . These findings have implication s for T replacement therapy and male contraception", "UNLABELLED Anecdotal reports of \" roid rage \" and violent crimes by and rogenic steroid users have brought attention to the relationship between anabolic steroid use and angry outbursts . However , testosterone effects on human aggression remain controversial . Previous studies have been criticized because of the low and rogen doses , lack of placebo control or blinding , and inclusion of competitive athletes and those with preexisting psychopathology . To overcome these pitfalls , we used a double-blind , placebo-controlled design , excluded competitive athletes and those with psychiatric disorders , and used 600 mg testosterone enanthate (TE)/week . Forty-three eugonadal men , 19 - 40 yr , were r and omized to 1 of 4 groups : Group I , placebo , no exercise ; Group II , TE , no exercise ; Group III , placebo , exercise ; Group IV , TE plus exercise . Exercise consisted of thrice weekly strength training sessions . The Multi-Dimensional Anger Inventory ( MAI ) , which includes 5 different dimensions of anger ( inward anger , outward anger , anger arousal , hostile outlook , and anger eliciting situations ) , and a Mood Inventory ( MI ) , which includes items related to mood and behavior , were administered to subjects before , during , and after the 10 week intervention . The subject 's significant other ( spouse , live-in partner , or parent ) also answered the same questions about the subject 's mood and behavior ( Observer Mood Inventory , OMI ) . No differences were observed between exercising and nonexercising and between placebo and TE treated subjects for any of the 5 subdomains of MAI . Overall there were no significant changes in MI or OMI during the treatment period in any group . CONCLUSION Supraphysiological doses of testosterone , when administered to normal men in a controlled setting , do not increase angry behavior . These data do not exclude the possibility that still higher doses of multiple steroids might provoke angry behavior in men with preexisting psychopathology", "The present study assessed the effects of supraphysiologic doses of testosterone on aggressive responding in a controlled laboratory setting . Eight male subjects received gradually increasing doses of testosterone cypionate ( 150 mg/week for two weeks , 300 mg/week for two weeks , and 600 mg/week for two weeks ) or placebo using a double-blind , r and omized , cross-over design . Subjects were tested both before and after the series of injections . During the experimental session subjects could press a button to accumulate points exchangeable for money ( non-aggressive response ) or press another button to subtract points from a fictitious opponent ( aggressive response ) . Aggressive responding was instigated by subtracting points from the subject which was attributable to the fictitious opponent . Testosterone administration result ed in a significantly higher number of aggressive responding compared to placebo", "INTRODUCTION In short-term studies , testosterone replacement therapy has been shown to protect male subjects from exercise-induced ischaemia and modify cardiovascular risk factors such as insulin resistance , fat mass and lipid profiles . METHODS This r and omised parallel group controlled trial was design ed to assess the treatment effect of testosterone therapy ( Nebido ) compared with placebo in terms of exercise-induced ischaemia , lipid profiles , carotid intima-media thickness ( CIMT ) and body composition during 12 months treatment in men with low testosterone levels and angina . RESULTS A total of 15 men were recruited but 13 ( n=13 ) reached adequate duration of follow-up ; seven were treated with testosterone and six with placebo . Testosterone increased time to ischaemia ( 129+/-48 s versus 12+/-18 , P=0.02 ) and haemoglobin ( 0.4+/-0.6 g/dl versus -0.03+/-0.5 , P=0.04 ) , and reduced body mass index ( -0.3 kg/m(2 ) versus 1.3+/-1 , P=0.04 ) and triglycerides ( -0.36+/-0.4 mmol/l versus 0.3+/-1.2 , P=0.05 ) . The CIMT decreased in the testosterone group more than placebo , but full between group analyses suggested this was only a statistical trend ( -0.5+/-0.1 vs -0.09+/-0.06 , P=0.16 ) . There were no significant effects on serum prostate specific antigen , total or high-density lipoprotein cholesterol ; or on mood and symptom scores as assessed by Seattle Angina Score and EuroQol . CONCLUSION The protective effect of testosterone on myocardial ischaemia is maintained throughout treatment without decrement . Previously noted potentially beneficial effects of testosterone on body composition were confirmed and there were no adverse effects", "Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome ( AIDS ) wasting syndrome ( AWS ) . Testosterone and exercise increase muscle mass in men with AWS , with unclear effects on muscle composition . We examined muscle composition in 54 eugonadal men with AWS who were r and omized to 1 ) testosterone ( 200 mg i m weekly ) or placebo and simultaneously to 2 ) resistance training or no training in a 2 x 2 factorial design . At baseline and after 12 wk , we performed assessment s of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition . Leaner muscle has greater attenuation . Baseline muscle attenuation correlated inversely with whole body fat mass ( r = -0.52 , P = 0.0001 ) . This relationship persisted in a model including age , body mass index , testosterone level , viral load , lean body mass , and thigh muscle cross-sectional area ( P = 0.02 ) . Testosterone ( P = 0.03 ) and training ( P = 0.03 ) increased muscle attenuation . These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training . Anabolic therapy in these patients increases muscle leanness", "Background : Treatment-resistant depression is a persistent clinical problem . Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant supplement , although this strategy has received limited systematic study . Objective : The aim of the study was to examine the mood effects of testosterone supplementation to a serotonergic antidepressant in men with treatment-resistant depression . Method : Twenty-six healthy adult men with major depressive disorder , partial or nonresponse to 2 adequate antidepressant trials during the current episode , and currently using a selective serotonin reuptake inhibitor were r and omized under double-blind conditions to receive intramuscular injections of escalating doses of testosterone or placebo , in addition to their existing selective serotonin reuptake inhibitor regimen , for 6 weeks . The main outcome measure was the Hamilton Rating Scale for Depression score . Results : The mean age was 46.4 ± 10.8 years ; mean total testosterone level , 417.5 ± 197 ng/dL ; mean baseline Hamilton Rating Scale for Depression score , 22.2 ± 5.2 ; and median duration of the current depressive episode , 6.3 ± 10.6 years . Hamilton Rating Scale for Depression scores decreased significantly in both testosterone ( 8.4 ) and placebo ( 7.4 ) groups . Antidepressant response , defined as a 50 % decline in Hamilton Rating Scale for Depression score , was achieved by 53.8 % ( 7/13 ) in the testosterone group and 23.1 % ( 3/13 ) in the placebo group ( P = 0.226 ) . Conclusion : Both injectable testosterone and placebo supplementation to selective serotonin reuptake inhibitor were associated with improvement in mood ; group differences were not distinguishable in this small sample of predominantly eugonadal men with treatment-resistant depression", "OBJECTIVE Testosterone supplementation may produce antidepressant effects in men , but until recently it has required cumbersome parenteral administration . In an 8-week r and omized , placebo-controlled trial , the authors administered a testosterone transdermal gel to men aged 30 - 65 who had refractory depression and low or borderline testosterone levels . METHOD Of 56 men screened , 24 ( 42.9 % ) displayed morning serum total testosterone levels of 350 ng/dl or less ( normal range=270 - 1070 ) . Of these men , 23 entered the study . One responded to an initial 1-week single-blind placebo period , and 22 were subsequently r and omly assigned : 12 to 1 % testosterone gel , 10 g/day , and 10 to identical-appearing placebo . Each subject continued his existing antidepressant regimen . Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial . RESULTS The groups were closely matched on baseline demographic and psychiatric measures . Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo . These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale . A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory . One subject assigned to testosterone reported increased difficulty with urination , suggesting an exacerbation of benign prostatic hyperplasia ; no other subject reported adverse events apparently attributable to testosterone . CONCLUSIONS These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels", "The effect of acute testosterone administration on exercise-induced myocardial ischemia was assessed in 14 men with coronary artery disease and low plasma testosterone concentrations in a study of r and omized , double-blind , crossover design . Testosterone increased time to 1-mm ST-segment depression compared with placebo by 66 ( 15 to 117 ) seconds ( p = 0.016 ) , suggesting a beneficial effect of testosterone on myocardial ischemia in these patients", "A double-blind comparison was made of the effects of testosterone undecanoate ( TU ) and placebo on sexual potency of 29 impotent men ages 45–75 . The main criteria for inclusion in the study were a reduced or nonexistent capacity to have an erection during intercourse and no clinical signs of endocrinological pathology . All patients received placebo for 2 weeks . Then TU was given at a daily dose of 120 mg to 13 patients selected at r and om while the other patients continued to receive placebo . After 8 weeks all patients received placebo again for 2 weeks . An improvement in sexual potency was reported by five patients given TU and eight patients given placebo , with no significant differences between the groups . Treatment with TU influenced neither the hypothalamic-pituitary-gonadal axis , as judged by levels of prolactin , LH , FSH , and the LHRH-induced LH/FSH response , nor depression , anxiety , and somatic scores or performance tests . The only specific effect of TU treatment was to decrease the total plasma testosterone level . The present findings show pharmacotherapy with and rogens to be no more effective than placebo in restoring sexual potency to sexually impotent men without and rogen deficiency . Further studies may be needed to eluci date fully the effects of and rogen administration on psychological and endocrinological variables in such patients", "PURPOSE We compare the efficacy of testosterone gel ( T-gel ) versus placebo as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone . MATERIAL S AND METHODS A r and omized , placebo controlled , double-blind , parallel group , multicenter study was performed . A total of 75 hypogonadal men ( 18 to 80 years old , morning serum total testosterone 400 ng/dl or less ) with confirmed lack of response to sildenafil monotherapy were r and omized ( 1:1 ) to receive a daily dose of 1 % T-gel or 5 gm placebo gel as adjunctive therapy to 100 mg sildenafil during a 12-week period . Subjects were evaluated for sexual function , primarily based on the International Index of Erectile Function ( IIEF ) , quality of life and serum testosterone levels at baseline and weeks 4 , 8 and 12 . RESULTS Testosterone treated subjects had greater improvement in erectile function compared to those who received placebo , reaching statistical significance at week 4 ( 4.4 vs 2.1 , p = 0.029 , 95.1 % CI 0.3 , 4.7 ) . Similar trends were observed for improvements in orgasmic function , overall satisfaction , total IIEF score and percentage of IIEF responders . T-gel significantly ( p total and free testosterone levels throughout the study , although no significant correlations were made between testosterone levels and the IIEF at end point . CONCLUSIONS T-gel taken with sildenafil may be beneficial in improving erectile function in hypogonadal men with erectile dysfunction who are unresponsive to sildenafil alone", "INTRODUCTION Addition of testosterone ( T ) may improve the action of phosphodiesterase type 5 inhibitors ( PDE5-Is ) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels . AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant . METHODS A multicenter , multinational , double-blind , placebo-controlled study of 173 men , 45 - 80 years , nonresponders to treatment with different PDE5-Is , with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day ( OAD ) for 4 weeks ; if not successful , they were r and omized in a double-blind , placebo-controlled design to receive placebo or a 1 % hydroalcoholic T gel ( 50 mg/5 g gel ) , to be increased to 10 mg T if results were clinical ly unsatisfactory . Main Outcomes Measures . Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses ( Sexual Encounter Profile 3 question ) . RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups . In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL , no additional effect of T administration to men optimally treated with PDE5-Is was encountered . The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks . Furthermore , addition of T to this PDE5-I regimen is beneficial , but only in hypogonadal men with baseline T levels ≤ 3", "PURPOSE Determine the independent and combined effects of progressive resistance muscle strength training ( PRMST ) and testosterone on strength , muscle mass , and function in hypogonadal elderly male recuperative care patients . METHODS Between 1999 and 2004 , 71 subjects ( mean age 78.2 + /- 6.4 yr , 86 % white ) were enrolled . After baseline one-repetition maximum ( 1RM ) strength testing and then r and omization to one of four treatment groups ( low-resistance ( 20 % of the 1RM ) exercises and weekly injections of either 100 mg of testosterone enanthate or placebo or high-intensity PRMST ( > or = 80 % 1RM ) and weekly injections ) , each subject received training and injections for 12 wk . RESULTS Ten subjects withdrew from the study before its completion . Based on intent-to-treat analyses , strength improved in all groups , but was greater with high-intensity PRMST compared with low-resistance exercise ( e.g. , leg press , ( mean + /- SE ) , 28 + /- 4 vs 13 + /- 4 % , P = 0.009 ) . Although testosterone led to significantly greater increases in midthigh cross-sectional muscle area compared with placebo ( 7.9 + /- 1.3 vs 2.4 + /- 1.4 % , P = 0.005 ) , it produced only a nonsignificant trend toward greater strength gains ( e.g. , leg press 25 + /- 4 vs 16 + /- 4 % , P = 0.144 ) . Change in aggregate functional performance score ( the sum of 4 functional performance test scores ) did not differ between the four intervention groups nor with high-intensity PRMST compared with low-resistance exercise ( 7 + /- 5 vs 15 + /- 5 % , P = 0.263 ) . There was not a significant interaction between exercise and testosterone for any outcome . CONCLUSION High-intensity PRMST is as safe and well tolerated as a similarly structured low-resistance exercise regimen for very frail elderly patients , but produces greater muscle strength improvements . The addition of testosterone leads to greater muscle size and a trend toward greater strength but did not produce a synergistic interaction with exercise . Neither intervention had a significant effect on functional performance", "Clinical studies suggest there may be a threshold concentration of serum testosterone below which replacement will result in skeletal and psychological benefit . We evaluated the response to testosterone in men with borderline hypogonadism . A r and omized double-blind placebo-controlled trial in 39 men over age 40 years presenting with sexual dysfunction and a borderline low testosterone level ( total testosterone Patients were r and omized to Testoderm TTS body patch ( 5 mg/day , n = 20 ) or a placebo patch ( n = 19 ) for 6 months , followed by open-label testosterone replacement for a further 6 months in all patients . During the placebo-controlled phase of the study serum testosterone increased significantly on testosterone vs. placebo treatment ( p = 0.004 ) ; this was associated with a decrease in total body fat mass ( p = 0.019 ) and increase in haemoglobin level ( p = 0.036 ) . There were no significant changes in lean body mass , markers of bone turnover , and measures of bone mineral density ( BMD ) . There was evidence of difference in quality of life according to the Male Erectile Dysfunction Quality of Life question naire ( MEDQoL score , p = 0.017 ) , mainly accounted for by deterioration in the placebo arm . When the active treatment period was combined for placebo and testosterone groups , the within-patient analysis showed a significant effect of testosterone to decrease markers of bone resorption ( uNTX/Cr , p = 0.007 ; iFDPD/Cr , p = 0.0006 ) and to increase lean body mass ( p = 0.001 ) . There was little convincing evidence from this study that testosterone replacement is likely to have major benefit in men over age 40 years with borderline hypogonadism and sexual dysfunction . However , there was evidence of suppression in bone resorption and hence longer and larger studies are needed to examine its effect on BMD", "BACKGROUND Anabolic and rogen steroid abuse is associated with multiple psychiatric symptoms and is a significant public health problem . The biological mechanisms underlying behavioral symptom development are poorly understood . SUBJECTS AND METHODS We examined levels of monoamine metabolites , neurohormones , and neuropeptides in the cerebrospinal fluid ( CSF ) of 17 healthy men , at baseline and following 6 days of methyltestosterone ( MT ) administration ( 3 days of 40 mg/d , then 3 days of 240 mg/d ) . Subjects received MT or placebo in a fixed sequence , with neither subjects nor raters aware of the order . Potential relationships were examined between CSF measures , CSF MT levels , and behavioral changes measured on a visual analog scale . RESULTS Following MT administration , levels of 3-methoxy-4-hydroxyphenylglycol ( MHPG ) were significantly lower ( mean + /- SD , 103.8 + /- 47 vs 122.0 + /- 50.7 pmol/mL ; P 5-hydroxyindoleacetic acid ( 5-HIAA ) levels were significantly higher ( mean + /- SD , 104.7 + /- 31.3 vs 86.9 + /- 23.6 pmol/mL ; P CSF levels of corticotropin , norepinephrine , cortisol , arginine vasopressin , prolactin , corticotropin-releasing hormone , beta-endorphin , and somatotropin release-inhibiting factor . Changes in CSF 5-HIAA significantly correlated with increases in \" activation \" symptoms ( energy , sexual arousal , and diminished sleep ) ( r = 0.55 ; P = .02 ) . No significant correlation was observed between changes in CSF and plasma MT , CSF MHPG , and behavioral symptoms . CONCLUSIONS Short-term anabolic and rogenic steroid use affects brain neurochemistry , increasing CSF 5-HIAA and decreasing MHPG . Changes in 5-HIAA levels caused by anabolic and rogenic steroids are related to the behavioral changes we observed . In this small sample , we did not observe a significant relationship between behavioral measures and either dose of MT or CSF and plasma levels of MT", "CONTEXT There is a compelling need for therapies that prevent , defer the onset , slow the progression , or improve the symptoms of Alzheimer disease ( AD ) . OBJECTIVE To evaluate the effects of testosterone therapy on cognition , neuropsychiatric symptoms , and quality of life in male patients with mild AD and healthy elderly men . DESIGN Twenty-four-week , r and omized , double-blind , placebo-controlled , parallel-group study . SETTING Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles , San Francisco , and Irvine . PATIENTS OR OTHER PARTICIPANTS Sixteen male patients with AD and 22 healthy male control subjects . Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics . INTERVENTION Testosterone and placebo , in the form of hydroalcoholic gel ( 75 mg ) , were applied daily to the skin of the participants . MAIN OUTCOME MEASURES Instruments assessing cognitive functioning ( Alzheimer 's Disease Assessment Scale-Cognitive Subscale , California Verbal Learning Test , Block Design Subtest , Judgment of Line Orientation , Developmental Test of Visual-Motor Integration ) , neuropsychiatric symptoms ( Neuropsychiatric Inventory ) , global functioning ( Clinician 's Interview-Based Impression of Change ) , and quality of life ( Quality of Life-Alzheimer Disease Scale ) . RESULTS For the patients with AD , the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality -of-life scale ( P = .01 ) . No significant treatment group differences were detected in the cognitive scores at end of study , although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo . In the healthy control group , a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group ( P = .09 ) compared with placebo treatment . No difference between the treatment groups was detected in the remaining outcome measures . Testosterone treatment was well tolerated with few adverse effects relative to placebo . CONCLUSIONS Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD . Testosterone had minimal effects on cognition", "Abstract Symptomatic and rogen deficiency is common in patients taking opioid analgesics , as these drugs potently suppress the hypothalamic – pituitary – gonadal axis . However , the efficacy of testosterone replacement in this setting remains unclear . The objective of this trial was to evaluate the efficacy of testosterone replacement on pain perception and other and rogen-dependent outcomes in men with opioid-induced and rogen deficiency . We conducted a r and omized , double-blind , parallel placebo-controlled trial at an outpatient academic research center . Participants were men aged 18 to 64 years on opioid analgesics for chronic noncancer pain , and total testosterone levels were Participants were r and omly assigned to 14 weeks of daily transdermal gel that contained 5 g of testosterone or placebo . Primary outcomes were changes in self-reported clinical pain and objective ly assessed pain sensitivity . Sexual function , quality of life , and body composition were also assessed . The mean age was 49 years . The median total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and 251 ng/dL and 43 pg/mL in the testosterone and placebo arm , respectively . Of the 84 r and omized participants , 65 had follow-up data on efficacy outcomes . Compared with men assigned to the placebo arm , those assigned to testosterone replacement experienced greater improvements in pressure and mechanical hyperalgesia , sexual desire , and role limitation due to emotional problems . Testosterone administration was also associated with an improvement in body composition . There were no between-group differences in changes in self-reported pain . In conclusion , in men with opioid-induced and rogen deficiency , testosterone administration improved pain sensitivity , sexual desire , body composition , and aspects of quality of life", "The prevalence and course of sexual dysfunction was evaluated in 221 alcoholic cirrhotic men participating in a double-blind , placebo-controlled study on the effect of oral testosterone treatment on liver disease . At entry , 67 % ( 95 % confidence limits , 61%-74 % ) complained of sexual dysfunction . Sexual dysfunction was significantly ( p less than 0.05 ) associated with lower serum concentrations of testosterone , non-protein-bound testosterone , and non-sex hormone-binding globulin-bound testosterone . The significant associations between sexual dysfunction and non-protein-bound and non-sex hormone-binding globulin-bound testosterone concentrations disappeared , however , when age , ethanol consumption , and severity of liver disease were included as covariates in the analysis . During follow-up ( median 30 mo , range 1 - 48 mo ) sexual dysfunction improved significantly ( p less than 0.05 ) at 6 , 12 , and 24 mo . Furthermore , the reported libido and erectile and ejaculatory function improved significantly at the end of the follow-up period ( p less than 0.01 ) . However , the testosterone-treated patients did not differ significantly from the placebo-treated patients regarding any of the changes in sexual function . In conclusion , oral testosterone treatment does not significantly influence the type or course of sexual dysfunction in alcoholic cirrhotic men . However , sexual function improved after reduction of ethanol consumption in these patients", "The cardiovascular effects of testosterone treatment are debated . Osteoprotegerin ( OPG ) is an independent marker of cardiovascular risk . We investigated the effect of testosterone therapy on OPG levels in aging men with low normal bioavailable testosterone levels . A r and omized , double-blinded , placebo-controlled study of 6 months testosterone therapy ( gel ) in 38 men aged 60 - 78 years with bioavailable testosterone 94 cm was performed . Clinical evaluation , OPG , and C-reactive protein ( CRP ) measurements were carried out . Lean body mass ( LBM ) , total fat mass , and bone mineral density ( BMD ) were established by dual X-ray absorptiometry . Visceral adipose tissue ( VAT ) and subcutaneous adipose tissue ( SAT ) were measured by magnetic resonance imaging . Power calculation was based on an increase in LBM during testosterone therapy and responders were defined as testosterone treated patients with increased LBM ( Δ LBM positive ) , n=14 . Data are presented as median ( interquartile range ) . Testosterone therapy decreased total fat mass and SAT , whereas VAT was unchanged ( n=38 ) . OPG levels decreased during testosterone therapy ( from 2.0 ( 1.9 - 2.5 ) to 1.9 ( 1.6 - 2.2 ) ng/ml , p whereas CRP levels were unchanged ( n=38 ) . In responders to testosterone therapy ( n=14 ) , ΔOPG levels were inversely associated with ΔSAT ( r= - 0.60 , p=0.03 ) and positively associated with ΔVAT ( r=0.56 , p=0.04 ) . OPG levels decreased during testosterone therapy suggesting decreased cardiovascular risk . Decreased OPG levels were associated with changes in regional fat distribution and future studies are needed to further evaluate the association between OPG and regional fat mass distribution", "OBJECTIVES Older patients undergoing knee replacement surgery can recover more slowly than younger patients and require extended rehabilitation . Because administration of supraphysiological testosterone ( T ) dramatically increases strength , we hypothesized that preoperative T therapy would improve functional recovery and reduce hospital stay in older men undergoing knee replacement surgery . DESIGN Double-blinded , placebo-controlled pilot trial . SETTING A Veterans Affairs orthopedics clinic and inpatient postoperative unit . PARTICIPANTS Twenty-five men , mean age 70 , undergoing elective knee replacement . INTERVENTION Preoperative , supraphysiological T administration ( 600 mg T enanthate intramuscularly weekly for 4 weeks ) or sesame oil placebo . MEASUREMENTS Length of hospital stay and functional ability by Functional Independence Measure ( FIM ) score . RESULTS Mean length of hospital stay + /- st and ard deviation was nonsignificantly reduced in the T group ( 5.9 + /- 2.4 days vs 6.8 + /- 2.5 days ; P = .15 ) . At postoperative Day 3 , there was a significant improvement in ability to st and ( mean FIM score 5.2 + /- 1.0 vs 4.0 + /- 1.1 ; P = .04 ) and trends towards improvements in walking and stair climbing in the T group . There were no complications attributable to T therapy . CONCLUSIONS In older men undergoing knee replacement surgery , preoperative supraphysiological T administration may confer some clinical benefit . Future studies using longer courses of preoperative T administration in larger numbers of older men undergoing knee replacement surgery are warranted", "BACKGROUND The role of sex hormones in the prevention of cognitive decline is uncertain . Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function . But , there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment . METHODS In this pilot study , 11 men ( mean age 80 + /- 5 years , range 73 - 87 years ) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl ( lower limit for adult normal range ) were r and omized to receive intramuscular testosterone ( 200 mg every 3 weeks ) or placebo for 12 weeks . Outcome measures included sex hormones ( testosterone , bioavailable testosterone , sex hormone binding globulin , estradiol , and estrone ) , Behave AD Question naire , Katz Activities of Daily Living , Geriatric Depression Scale , Digit Span , Clock Face Drawing , Clock Face Perception , Verbal Fluency , Trail-Making B , and International Prostate Symptom Score at baseline , 4 weeks , and 10 weeks . RESULTS All men completed the study . Total and bioavailable testosterone , estrone , and estradiol levels increased in men receiving testosterone , but no changes were detected in men receiving placebo . No significant changes were found in behavior following testosterone supplementation , nor was there evidence of change in depression or activities of daily living . No discernable changes were found in any of the cognitive tests . Symptoms of prostate hyperplasia remained unchanged in the testosterone ( 6.6 + 5.8 to 5.2 + 3.6 ; p = .39 ) and placebo ( 8.8 + 6.4 to 6.4 + 3.8 ; p = .15 ) groups , and prostate-specific antigen levels did not change significantly . CONCLUSION No significant changes in behavior , function , depression , or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment . This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors", "BACKGROUND It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range . The objective of this study was to compare the cognitive responses of older , eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation . DESIGN R and omized , double-blind , placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline . SETTING Community dwelling participants . PARTICIPANTS Fifty-seven healthy , eugonadal , community dwelling male volunteers , mean age 67 years ( + /-11 years ) . INTERVENTIONS Participants were r and omized to receive weekly intramuscular ( i.m . ) injections of either 50 , 100 or 300 mg T enanthate or placebo ( saline ) injection for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , weeks 3 and 6 of treatment and after 6 weeks of wash-out . MAIN OUTCOME MEASURES Performance on cognitive tests of verbal and spatial memory . RESULTS Men with moderate increases in serum T and /or its metabolites demonstrated significant improvements in verbal and spatial memory . In contrast , men with large or low increases in circulating T levels , failed to demonstrate significant changes in memory . CONCLUSION These results suggest that in healthy older men , beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels . Large or no to low increases in T levels do not appear to appreciably effect cognition", "The objective of the study was to investigate the effects of dihydrotestosterone ( DHT ) gel on general well-being , sexual function , and the prostate in aging men . A total of 120 men participated in this r and omized , placebo-controlled study ( 60 DHT and 60 placebo ) . All subjects had nocturnal penile tumescence once per week or less , and ropause symptoms , and a serum T level of 15 nmol/liter or less and /or a serum SHBG level greater than 30 nmol/liter . The mean age was 58 yr ( range , 50 - 70 yr ) . Of these subjects , 114 men completed the study . DHT was administered transdermally for 6 months , and the dose varied from 125 - 250 mg/d . General well-being symptoms and sexual function were evaluated using a question naire , and prostate symptoms were evaluated using the International Prostate Symptoms Score , transrectal ultrasonography , and assay of serum prostate-specific antigen . Early morning erections improved transiently in the DHT group at 3 months of treatment ( P ability to maintain erection improved in the DHT group compared with the placebo group ( P general well-being between the placebo and the DHT group . Serum concentrations of LH , FSH , E2 , T , and SHBG decreased significantly during DHT treatment . Treatment with DHT did not affect liver function or the lipid profile . Hemoglobin concentrations increased from 146.0 + /- 8.2 to 154.8 + /- 11.4 g/liter , and hematocrit from 43.5 + /- 2.5 % to 45.8 + /- 3.4 % ( P Prostate weight and prostate-specific antigen levels did not change during the treatment . No major adverse events were observed . Transdermal administration of DHT improves sexual function and may be a useful alternative for and rogen replacement . As estrogens are thought to play a role in the pathogenesis of prostate hyperplasia , DHT may be beneficial , compared with aromatizing and rogens , in the treatment of aging men", "BACKGROUND Hypogonadism and anemia are common comorbid conditions in dialysis patients . Testosterone replacement may improve such clinical parameters as anemia , sarcopenia , and low libido . Additionally , by increasing hemoglobin levels , testosterone replacement may allow for a dose reduction in recombinant human erythropoietin ( rHuEPO ) , thereby reducing cost . METHODS This phase IV , single-center , placebo-controlled , double-blind study assessed the effect of transdermal testosterone on serum testosterone levels , rHuEPO dose required to maintain hemoglobin level , bone mineral content , lean body mass and fat content , cholesterol level , sexual function , and mood . Forty hypogonadal male hemodialysis patients who were administered rHuEPO were r and omly assigned to 100 mg of topical 1 % testosterone gel ( Testim ; Auxilium Pharmaceuticals , Norristown , PA ) or placebo , applied daily for 6 months . RESULTS Forty men with a mean age of 56 years and baseline serum testosterone level less than 300 ng/dL ( In men assigned to administration of transdermal testosterone , there was an increase beyond that in the placebo group in mean serum testosterone ( 77.1 ng/dL [ 2.7 nmol/L ] ) , dihydrotestosterone ( DHT ; 0.8 nmol/L ) , and estradiol levels ( 6.3 pg/mL [ 23.0 pmol/L ] ) and a decrease in mean serum luteinizing hormone levels ( -3.1 IU/L ) . Compared with subjects administered placebo , participants on testosterone replacement therapy did not show an appreciable change in rHuEPO dose ( mean difference adjusted for baseline values , 12.6 U/kg/wk ; P = 0.73 ) , bone mineral density , lean body mass or fat content , cholesterol level , sexual function , or mood . CONCLUSION Daily administration of 100 mg of topical 1 % testosterone gel for 6 months failed to significantly increase serum testosterone or DHT levels in hypogonadal men with end-stage renal disease . Treatment with transdermal testosterone did not impact on rHuEPO requirement or clinical parameters in this small placebo-controlled study . Greater serum testosterone levels may be required to show clinical benefit in men with end-stage renal disease", "In a single-blind , placebo-controlled study , the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate ( And riol ® ) on the quality of life of men with testosterone deficiency were evaluated . The subjects included ten men with primary hypogonadism and 29 with and ropause with sexual dysfunction as the most common problem . The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Question naire for and rogen deficiency in aging males ( ADAM ) . Digital rectal examination ( DRE ) was performed and serum testosterone , prostate-specific antigen ( PSA ) and liver profile were monitored . Testosterone undecanoate treatment ( n = 33 ) significantly improved sexual dysfunction and symptom scores of metabolic , cardiopulmonary , musculo-skeletal and gastrointestinal functions compared to baseline and to placebo ( n = 6 ) . ADAM score also significantly improved after 3 months of treatment . Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group . In the placebo group , no significant changes compared to baseline were found for testosterone levels and QoL question naires . No abnormal findings were detected on DRE or laboratory findings in either group . Adverse events , such as gastrointestinal problems and fatigue , were mild and self-limiting . It is concluded that and rogen supplement therapy with oral testosterone undecanoate ( And riol ) restores the quality of life through improvement of general body functions in men with testosterone deficiency", "A decline in testicular function is recognized as a common occurrence in older men . However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines . This study was undertaken to examine the year-long effects of testosterone administration in this patient population . Fifteen hypogonadal men ( mean age 68 + /- 6 yr ) were r and omly assigned to receive a placebo , and 17 hypogonadal men ( mean age 65 + /- 7 yr ) were r and omly assigned to receive testosterone . Hypogonadism was defined as a bioavailable testosterone placebo or 200 mg testosterone cypionate biweekly for 12 months . The main outcomes measured included grip strength , hemoglobin , prostate-specific antigen , leptin , and memory . Testosterone improved bilateral grip strength ( P hemoglobin ( P testosterone had greater decreases in leptin than those assigned to the control group ( mean + /- SEM : -2.0 + /- 0.9 ng/dL vs. 0.8 + /- 0.7 ng/dL ; P prostate-specific antigen or memory . Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study . Three of those seven withdrew because of an abnormal elevation in hematocrit . Testosterone supplementation improved strength , increased hemoglobin , and lowered leptin levels in older hypogonadal men . Testosterone may have a role in the treatment of frailty in males with hypogonadism ; however , older men receiving testosterone must be carefully monitored because of its potential risks", "OBJECTIVES The effects of supplemental testosterone on cognition , mood and wellbeing in ageing men are unclear . This study aim ed to assess the effect of 12-months of oral testosterone supplementation on cognitive function , mood and quality of life in elderly men with low-normal gonadal status , not specifically selected for cognitive or mood defects . METHODS A st and ard oral dose ( 80 mg twice daily ) of testosterone undecanoate ( TU ) or placebo was administered for one year to 76 healthy men 60 years or older . All men had a free testosterone index ( FTI ) of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . A neuropsychological assessment including the trail making test ( part B ) , visuospatial ( VSP ) block design test , mini mental state exam ( MMSE ) , Geriatric Depression Scale ( GDS ) , a 5-point Likert and a 10-point visual analogue quality of life ( QoL ) scale , along with serum hormone measurements were obtained at baseline , 6 , and 12 months . RESULTS Although calculated bioavailable testosterone ( cBT ) and FTI were higher , and muscle mass increased after 12 months , there was no difference in scores on the trail making or VSP block tests , the MMSE , GDS or either of the QoL scales between the testosterone and placebo group . There was no relationship between baseline cBT or FTI and treatment effect for any of the outcome measures . CONCLUSIONS 12-month supplementation with oral TU does not affect scores on visuospatial tests or mood and quality of life scales in older men with low-normal gonadal status ", "Objective : To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men . Background : Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass , osteoporosis , decreased sexual activity , and changes in cognition . Methods : Twenty-five healthy , community-dwelling volunteers , aged 50 to 80 years , completed a r and omized , double-blind , placebo-controlled study . Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo ( saline ) for 6 weeks . Cognitive evaluations were conducted at baseline , week 3 , and week 6 of treatment by use of a battery of neuropsychologic tests . Results : Circulating total testosterone was raised an average of 130 % from baseline at week 3 and 116 % at week 6 in the treatment group . Because of aromatization of testosterone , estradiol increased an average of 77 % at week 3 and 73 % at week 6 in the treatment group . Significant improvements in cognition were observed for spatial memory ( recall of a walking route ) , spatial ability ( block construction ) , and verbal memory ( recall of a short story ) in older men treated with testosterone compared with baseline and the placebo group , although improvements were not evident for all measures . Conclusions : The results suggest that short-term testosterone administration enhances cognitive function in healthy older men . However , it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels , or both . The potential role of testosterone vs its metabolites on cognition requires further research", "Objective : To determine the contribution of conversion of testosterone ( T ) to estradiol on cognitive processing in a population of healthy older men who received T supplementation . Methods : Sixty healthy , community-dwelling volunteers aged 50 to 90 years completed a r and omized , double-blind , placebo-controlled study . Participants were r and omized to receive weekly IM injections of 100 mg T enanthate plus daily oral placebo pill ( T group , n = 20 ) , 100 mg testosterone enanthate plus 1 mg daily of anastrozole , an aromatase inhibitor ( oral pill ) , to block the conversion of T to estradiol ( AT group , n = 19 ) , or saline injection and placebo pill ( placebo group , n = 21 ) for 6 weeks . Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline , week 3 and week 6 of treatment , and after 6 weeks of washout . Results : Circulating total T was increased from baseline an average of 238 % in the T and AT treatment groups . Estradiol increased an average of 81 % in the T group and decreased 50 % in the AT group during treatment . Significant improvements in spatial memory were evident in the AT and T treatment groups . However , only the group with elevated estradiol levels ( T group ) demonstrated significant verbal memory improvement . Conclusion : In healthy older men , improvement in verbal memory induced by testosterone administration depends on aromatization of testosterone to estradiol , whereas improvement in spatial memory occurs in the absence of increases in estradiol", "The current study evaluates the efficacy and safety of testosterone ( T ) gel 1 % augmentation on depressive symptoms and quality of life in treatment-resistant , depressed , hypogonadal men older than 50 years of age who are receiving antidepressants . The authors hypothesized that T augmentation would improve depressive symptoms and quality of life . Eighteen hypogonadal men entered the study who had had an adequate trial of antidepressant therapy and had significant depressive symptoms . Participants were continued on their antidepressant and were r and omized to receive either placebo or active T gel ( 5 g ) to be applied once a day . Participants were tested on 6 occasions : screening visit , an initial session ( pretreatment ) , at 6 and 12 weeks during the first treatment condition , and at 18 and 24 weeks during the crossover condition . The authors found a significant improvement in depressive symptoms from baseline to 12 weeks of testosterone treatment . However , a statistical difference between placebo and testosterone treatment phases was not demonstrated . The limitations of the study , including the chronicity and severity of patients ’ depression , variability in T levels , and a small sample size , probably influenced the ability to detect a discernable difference . Nevertheless , the study shows that T gel augmentation may be helpful in hypogonadal males with depression . ( J Geriatr Psychiatry Neurol 2005 ; 18:20 - 24", "Objective : Weight loss in HIV-infected patients is extremely common and is associated with increased morbidity and mortality . Decreased testosterone concentrations occur commonly in patients with HIV disease and are associated with weight loss . This study assessed the effect of testosterone therapy on HIV associated weight loss in patients with AIDS . Methods : Forty HIV-seropositive patients with CD4 + counts of in a double-blind manner to receive 200 mg of testosterone cypionate or placebo intramuscularly every 2 weeks for 3 months . Patients were then crossed to receive the alternate treatment for the next 3 months . Outcome variables included weight , skin fold measurement , a quality -of-life question naire , Karnofsky score , T-cell subset analysis , complete blood count , routine blood chemistry measurements and free testosterone concentration . Results : Thirty-nine patients entered the study . Of these , 35 completed the first 3-month period ( 18 on placebo , 17 on testosterone ) and 23 completed the whole 6 month trial . Analysis of these 23 patients did not show any significant differences between testosterone and placebo treatment . Analysis of the first 3 months only for the 35 patients who completed it did not show any significant difference between the effects of testosterone and placebo treatment on weight gain . Patients treated with testosterone reported improved overall well-being ( P = 0.03 ) and a trend towards increased muscle strength ( P = 0.08 ) . There was no difference between the two groups in terms of side-effects or other effects on hematopoetic , liver , renal or immune function . Conclusions : Treatment with testosterone cypionate compared with placebo did not result in significant weight gain . Testosterone supplementation did appear to produce an improved overall sense of well-being and possibly some increase in muscle strength . This r and omized , double-blinded study does not confirm the results of other recent studies which show potential benefits of testosterone and its analogs when used as a treatment for weight loss in HIV-positive patients", "This double-blind placebo controlled , cross-over study was carried out to assess the effect of testosterone administration on sexual behavior mood , and psychological symptoms in healthy men with erectile dysfunction . Biweekly injections of 200 mg of testosterone enanthate were given over a period of 6 weeks separated by a washout period of 4 weeks . Blood sample s for hormonal assessment , behavioral and psychological ratings were obtained prior to each injection . Luteinizing hormone remained significantly depressed but circulating testosterone had returned to baseline levels by 2 weeks following each hormonal injection . The ejaculatory frequency during the testosterone phase was statistically higher than during the placebo phase . There were marked , although statistically nonsignificant , increases in median frequency of reported sexual desire , masturbation , sexual experiences with partner , and sleep erections during the testosterone period . Testosterone did not have demonstrable effects on ratings of penile rigidity and sexual satisfaction . Mood variables and psychological symptoms did not change following hormonal administration . Results suggest that and rogen administration to eugonadal men with erectile dysfunction may activate their sexual behavior without enhancing erectile capacity and without effects on mood and psychological symptoms", "Because testosterone has an anabolic effect in myotonic dystrophy , we conducted a 12-month , r and omized , double-blind therapeutic trial of testosterone enanthate ( 3 mg/kg/wk ) in 40 men with myotonic dystrophy . We evaluated strength by manual muscle tests , quantitative myometry , pulmonary function , and quantitative functional assessment . A sustained , significant elevation of testosterone levels was produced but there was no effect on any measurement of muscle strength . Muscle mass as estimated by creatinine excretion and lean body mass ( 40 K method ) increased significantly . We conclude that testosterone does not improve strength in myotonic dystrophy despite increasing muscle mass", "Muscle wasting in older men may be related to and rogen deficiency . We have assessed the effect of testosterone replacement therapy on muscle function in the upper and lower limbs of older ( age > 60 years ) men with blood testosterone levels received testosterone enanthate 200 mg i.m . or placebo every 2 weeks in a double blind study over a 12-week period and underwent muscle testing every 4 weeks . A significant increase in blood levels of testosterone and a reduction in levels of sex hormone binding globulin occurred in the treatment group . Total body mass , haemoglobin and packed cell volume also increased significantly ( p h and grip strength , isometric strength of knee flexors and extensors or leg extensor power were seen in either group . Wide variability in all measures of muscle function were observed in these elderly men suggesting that very large study groups would be required to determine potential treatment benefits on muscle function", "Background : Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia , adverse clotting profiles , obesity , and insulin resistance . Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease . Objective : This r and omised single blind placebo controlled crossover study compared testosterone replacement therapy ( Sustanon 100 ) with placebo in 10 men with ischaemic heart disease and hypogonadism . Results : Baseline total testosterone and bioavailable testosterone were respectively 4.2 ( 0.5 ) nmol/l and 1.7 ( 0.4 ) nmol/l . After a month of testosterone , delta value analysis between testosterone and placebo phase showed that mean ( SD ) trough testosterone concentrations increased significantly by 4.8 ( 6.6 ) nmol/l ( total testosterone ) ( p = 0.05 ) and 3.8 ( 4.5 ) nmol/l ( bioavailable testosterone ) ( p = 0.025 ) , time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 ( 54 ) seconds ( p = 0.002 ) , and mood scores assessed with vali date d question naires all improved . Compared with placebo , testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor α with delta values of −0.41 ( 0.54 ) mmol/l ( p = 0.04 ) and −1.8 ( 2.4 ) pg/ml ( p = 0.05 ) respectively . Conclusion : Testosterone replacement therapy in hypogonadal men delays time to ischaemia , improves mood , and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor α ", "CONTEXT Observational studies have found lower rates of coronary heart disease ( CHD ) in postmenopausal women who take estrogen than in women who do not , but this potential benefit has not been confirmed in clinical trials . OBJECTIVE To determine if estrogen plus progestin therapy alters the risk for CHD events in postmenopausal women with established coronary disease . DESIGN R and omized , blinded , placebo-controlled secondary prevention trial . SETTING Outpatient and community setting s at 20 US clinical centers . PARTICIPANTS A total of 2763 women with coronary disease , younger than 80 years , and postmenopausal with an intact uterus . Mean age was 66.7 years . INTERVENTION Either 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate in 1 tablet daily ( n = 1380 ) or a placebo of identical appearance ( n = 1383 ) . Follow-up averaged 4.1 years ; 82 % of those assigned to hormone treatment were taking it at the end of 1 year , and 75 % at the end of 3 years . MAIN OUTCOME MEASURES The primary outcome was the occurrence of nonfatal myocardial infa rct ion ( MI ) or CHD death . Secondary cardiovascular outcomes included coronary revascularization , unstable angina , congestive heart failure , resuscitated cardiac arrest , stroke or transient ischemic attack , and peripheral arterial disease . All-cause mortality was also considered . RESULTS Overall , there were no significant differences between groups in the primary outcome or in any of the secondary cardiovascular outcomes : 172 women in the hormone group and 176 women in the placebo group had MI or CHD death ( relative hazard [ RH ] , 0.99 ; 95 % confidence interval [ CI ] , 0.80 - 1.22 ) . The lack of an overall effect occurred despite a net 11 % lower low-density lipoprotein cholesterol level and 10 % higher high-density lipoprotein cholesterol level in the hormone group compared with the placebo group ( each P CHD events in the hormone group than in the placebo group in year 1 and fewer in years 4 and 5 . More women in the hormone group than in the placebo group experienced venous thromboembolic events ( 34 vs 12 ; RH , 2.89 ; 95 % CI , 1.50 - 5.58 ) and gallbladder disease ( 84 vs 62 ; RH , 1.38 ; 95 % CI , 1.00 - 1.92 ) . There were no significant differences in several other end points for which power was limited , including fracture , cancer , and total mortality ( 131 vs 123 deaths ; RH , 1.08 ; 95 % CI , 0.84 - 1.38 ) . CONCLUSIONS During an average follow-up of 4.1 years , treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease . The treatment did increase the rate of thromboembolic events and gallbladder disease . Based on the finding of no overall cardiovascular benefit and a pattern of early increase in risk of CHD events , we do not recommend starting this treatment for the purpose of secondary prevention of CHD . However , given the favorable pattern of CHD events after several years of therapy , it could be appropriate for women already receiving this treatment to continue", "Purpose . Supplemental administration of and rogens has been advocated for men with sexual dysfunction ( SD ) and hypo and rogenism . The preponderance of evidence indicates that most delivery forms of testosterone ( T ) are effective but the role of dehydroepi and rosterone ( DHEA ) is controversial . A placebo-controlled , r and omized trial of oral and rogen ( T versus DHEA ) supplementation was carried out to determine their efficacy . Material s and methods . Eighty-six men with SD and decreased levels of serum T and /or DHEA , participated in a study receiving oral T undecanoate ( OTU ) ( n = 29 ) 80 mg twice daily , DHEA ( n = 28 ) 50 mg twice daily , or placebo ( n = 29 ) . Outcomes included evaluation of sexual performance by the International Index of Erectile Function ( IIEF ) , the And rogen Deficiency in the Aging Male ( ADAM ) , Aging Male Symtom Scale ( AMS ) , and Global Assessment Question naire ( GAQ ) question naires . Biochemical evaluations included measurement of T and DHEA , prolactin , gonadotropins , and PSA . Results . Seventy-nine men completed the study . There were no significant differences in outcomes as assessed by four different instruments : the ADAM , IIEF , AMS , and GAQ in regard to sexual interest or erectile function . Biochemically , a significant increase in serum DHEA between baseline and final visit was documented in the group receiving DHEA . The levels of T , on the other h and , increased insignificantly between entry and final visit in the T cohort . No biochemical changes were observed in the placebo group . Levels of PSA remained stable in all three groups . Conclusions . This study did not suggest a clinical benefit of OTU or DHEA supplementation in men with hypo and rogenism and SD . The recommended dose of OTU may have been inadequate or poorly absorbed . Increased doses or an alternative T delivery form may result in a different response", "BACKGROUND To determine the effect of oral testosterone supplementation on systemic low- grade inflammation measured by high-sensitive C-reactive protein ( hs-CRP ) in aging men with low testosterone levels . METHODS Two hundred thirty-seven men aged 60 to 80 years with a testosterone level of were recruited into a double-blind r and omized placebo-controlled trial . Participants were r and omized to either 4 capsules of 40 mg testosterone undecanoate ( And riol Testocaps , NV Organon , Oss , The Netherl and s ) or placebo daily for 26 weeks . Serum levels of hs-CRP were measured at baseline and at 26 weeks using a near-infrared particle immunoassay of the Synchron LX System ( Beckman Coulter , Fullteron , CA ) . RESULTS The median baseline hs-CRP level was 1.95 mg/L ( 0.30 - 6.43 ) in the testosterone group compared with 1.90 mg/L ( 0.40 - 5.91 ) in the placebo group . After 26 weeks of testosterone supplementation therapy , the 2 intervention groups were not statistically significantly different ( median hs-CRP 2.20 vs 2.00 mg/L , interquartile range 0.40 - 6.54 vs 0.50 - 5.70 , P = .36 ) . In subgroup analysis , neither baseline testosterone level , nor age , nor baseline CRP-level modified the effect of testosterone supplementation on CRP levels . CONCLUSION Oral testosterone undecanoate supplementation , in dosage of 160 mg daily for 26 weeks , does not increase hs-CRP levels in elderly men", "OBJECTIVE To examine the effects of hypnotic suggestions or the administration of testosterone or trazodone to impotent men with no detectable organic cause for the impotence . PATIENTS AND METHODS The study comprised 79 men in whom clinical and laboratory examinations revealed no organic cause for their impotence : 20 men ( mean age 38.7 + /- 11.47 years ) received testosterone , 21 men ( mean age 39.5 + /- 10.73 years ) received trazodone , 20 men ( mean age 34.2 + /- 11.69 years ) underwent hypnosis and 18 men ( mean age 39.1 + /- 11.46 years ) served as controls . They were assessed by interview 4 , 6 and 8 weeks after starting treatment : the patient 's reports were verified by interviewing their partners . RESULTS Men who received a placebo had a 39 % improvement in sexual function , while the rates of improvement in the treated groups were higher , but not significantly so . The success rates of testosterone and trazodone treatment and hypnotic suggestions were 60 % , 67 % and 80 % , respectively . CONCLUSION Although the improvement was not statistically significant , treatment with testosterone and trazodone could be used as an adjuvant therapy in nonorganic male sexual dysfunction . The only treatment superior to placebo seemed to be hypnosis . A more effective treatment may be obtained by combining these therapeutic modalities , but this needs further study", "CONTEXT Low testosterone levels in men have been associated with increased mortality . However , the influence of testosterone treatment on mortality in men with low testosterone levels is not known . OBJECTIVE The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels . DESIGN This was an observational study of mortality in testosterone-treated compared with untreated men , assessed with time-varying , adjusted Cox proportional hazards regression models . Effect modification by age , diabetes , and coronary heart disease was tested a priori . SETTING The study was conducted with a clinical data base that included seven Northwest Veterans Affairs medical centers . PATIENTS Patients included a cohort of 1031 male veterans , aged older than 40 yr , with low total testosterone [ ≤250 ng/dl ( 8.7 nmol/liter ) ] and no history of prostate cancer , assessed between January 2001 and December 2002 and followed up through the end of 2005 . MAIN OUTCOME MEASURE Total mortality in testosterone-treated compared with untreated men was measured . RESULTS Testosterone treatment was initiated in 398 men ( 39 % ) during routine clinical care . The mortality in testosterone-treated men was 10.3 % compared with 20.7 % in untreated men ( P a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone . After multivariable adjustment including age , body mass index , testosterone level , medical morbidity , diabetes , and coronary heart disease , testosterone treatment was associated with decreased risk of death ( hazard ratio 0.61 ; 95 % confidence interval 0.42 - 0.88 ; P = 0.008 ) . No significant effect modification was found by age , diabetes , or coronary heart disease . CONCLUSIONS In an observational cohort of men with low testosterone levels , testosterone treatment was associated with decreased mortality compared with no testosterone treatment . These results should be interpreted cautiously because residual confounding may still be a source of bias . Large , r and omized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels", "CONTEXT Physical frailty is associated with reduced muscle strength , impaired physical function , and quality of life . Testosterone ( T ) increases muscle mass and strength in hypogonadal patients . It is unclear whether T has similar effects in intermediate-frail and frail elderly men with low to borderline-low T. OBJECTIVE Our objective was to determine the effects of 6 months T treatment in intermediate-frail and frail elderly men , on muscle mass and strength , physical function , and quality of life . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled , parallel-group , single-center study . PARTICIPANTS PARTICIPANTS were community-dwelling intermediate-frail and frail elderly men at least 65 yr of age with a total T at or below 12 nmol/liter or free T at or below 250 pmol/liter . METHODS Two hundred seventy-four participants were r and omized to transdermal T ( 50 mg/d ) or placebo gel for 6 months . Outcome measures included muscle strength , lean and fat mass , physical function , and self-reported quality of life . RESULTS Isometric knee extension peak torque improved in the T group ( vs. placebo at 6 months ) , adjusted difference was 8.6 ( 95 % confidence interval , 1.3 - 16.0 ; P = 0.02 ) Newton-meters . Lean body mass increased and fat mass decreased significantly in the T group by 1.08 + /- 1.8 and 0.9 + /- 1.6 kg , respectively . Physical function improved among older and frailer men . Somatic and sexual symptom scores decreased with T treatment ; adjusted difference was -1.2 ( -2.4 to -0.04 ) and -1.3 ( -2.5 to -0.2 ) , respectively . CONCLUSIONS T treatment in intermediate-frail and frail elderly men with low to borderline-low T for 6 months may prevent age-associated loss of lower limb muscle strength and improve body composition , quality of life , and physical function . Further investigations are warranted to extend these results", "BACKGROUND Substantial loss of muscle mass occurs among men with AIDS wasting . OBJECTIVE To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting . DESIGN R and omized , controlled trial . SETTING University hospital . PATIENTS 54 eugonadal men with AIDS wasting ( weight 10 % ) . INTERVENTION In a 2 x 2 factorial design , patients were assigned to receive testosterone enanthate ( 200 mg/wk ) or placebo injections and progressive resistance training ( three times weekly ) or no training for 12 weeks . MEASUREMENTS Cross-sectional muscle area and other indices of muscle mass . RESULTS Cross-sectional muscle area increased in response to training compared with nontraining ( change in arm muscle mass , 499 + /- 349 mm2 vs. 206 + /- 264 mm2 [ P = 0.004 ] ; change in leg muscle mass , 1106 + /- 854 mm2 vs. 523 + /- 872 mm2 [ P = 0.045 ] ) and in response to testosterone therapy compared with placebo ( change in arm muscle mass , 512 + /- 371 mm2 vs. 194 + /- 215 mm2 [ P leg muscle mass , 1,236 + /- 881 mm2 vs. 399 + /- 729 mm2 [ P = 0.002 ] ) . Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo ( -0.03 + /- 0.13 mmol/L vs. 0.05 + /- 0.13 mmol/L [ -1 + /- 5 mg/dL vs. 2 + /- 5 mg/dL ] ; P= 0.011 ) and increased in response to training compared with nontraining ( 0.05 + /- 0.13 mmol/L vs. 0.00 + /- 0.16 mmol/L [ 2 + /- 5 mg/dL vs. 0 + /- 6 mg/dL ] ; P = 0.052 ) . CONCLUSIONS In contrast to anabolic therapies that may have adverse effects on metabolic variables , supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting", "PURPOSE Because the effects of and rogen replacement on lipoprotein levels are uncertain , we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men . SUBJECTS AND METHODS One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations > 1 SD below the mean for young men were r and omly assigned to receive either testosterone ( 54 men ; 6 mg/day ) or placebo ( 54 men ) transdermally in a double-blind fashion for 36 months . Serum concentrations of lipids and apolipoproteins were measured , and cardiovascular events recorded . RESULTS Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men , but the 3-year mean ( + /- SD ) decreases in the two groups ( testosterone treated , -17 + /- 29 mg/dL ; placebo treated , -12 + /- 38 mg/dL ) were not significantly different from each other ( P = 0.4 ) . Similarly , serum low-density lipoprotein ( LDL ) cholesterol levels decreased in both treatment groups , but the decreases in the two groups ( testosterone treated , -16 + /- 24 mg/dL ; placebo treated , -16 + /- 33 mg/dL ) were similar ( P = 1.0 ) . Levels of high-density lipoprotein ( HDL ) cholesterol , triglycerides , and apolipoproteins A-I and B did not change . Lipoprotein(a ) levels increased in both groups by similar amounts ( testosterone treated , 3 + /- 9 mg/dL ; placebo treated , 4 + /- 6 mg/dL ; P = 1.0 ) . The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men ( 9 events ) and the placebo-treated men ( 5 events ) during the 3-year study ( relative risk = 1.8 ; 95 % confidence interval : 0.7 to 5.0 ) . CONCLUSIONS As compared with placebo , transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured . The effect of testosterone treatment on cardiovascular events was unclear , because the number of events was small", "BACKGROUND Relative and rogen deficiency in ageing males is assumed to have adverse health effects . This study assessed the effect of 12 months ' st and ard dose , oral testosterone , on symptoms attributed to testosterone deficiency in older men with plasma testosterone levels in the low-normal range for young men . METHODS Testosterone undecanoate ( TU , 80 mg bid ) or placebo was administered for one year to 76 healthy men , 60 years or older , with a free testosterone index ( FTI ) of 0.3 - 0.5 and significant symptoms on a question naire design ed to evaluate and rogen deficiency ( ADAM ) . The ADAM was completed at baseline , 6 and 12 months . Hormone and safety data were collected at baseline , 1 , 3 , 6 and 12 months . RESULTS After 12 months , plasma total testosterone was unchanged in both groups and sex hormone binding globulin decreased in the testosterone group ( P = 0.01 ) . FTI and calculated bioavailable testosterone ( cBT ) were greater in the testosterone group as compared with the placebo group ( P = 0.021 and 0.025 , respectively ) . There was no significant difference in total symptom score between testosterone and placebo groups after 12 months of oral TU . However , there were trends toward improvements in sadness/grumpiness ( P = 0.063 ) , reduced erection strength ( P = 0.059 ) and decreased work performance symptoms ( P = 0.077 ) , particularly in men with baseline cBT levels below 3.1 nmol/l . CONCLUSIONS This study concludes that 80 mg bid oral TU does not improve overall ADAM question naire scores in older men with low-normal gonadal status . Oral TU may preserve mood and erectile function , as assessed by this question naire , particularly in men with the lowest testosterone levels", "A r and omized , double-blind , placebo-controlled trial was conducted to ( 1 ) evaluate efficacy and safety of transdermal testosterone gel ( And roGel ) for hypogonadal men in Taiwan , and ( 2 ) observe improvements in sexual function through international index of erectile function ( IIEF ) scores . Eligible hypogonadal men were r and omized to receive 50 mg/day transdermal testosterone gel ( TTG ) or placebo for 3 months . Primary end point was change from baseline in total testosterone ( TT ) and free testosterone ( FT ) . Secondary end points were change from baseline in serum hormone levels ( such as dihydrotestosterone ( DHT ) , estradiol ( E2 ) , luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) and sex-hormone-binding globulin ( SHBG ) ) and changes in IIEF scores . Safety evaluations included adverse events ( AEs ) and skin irritation assessment . Compared with baseline , the TTG group ( n=20 ) had statistically significant increases in mean TT levels at month 1 ( P=0.024 ) and month 2 ( P=0.025 ) , but no significant changes at month 3 . TT levels in the placebo group ( n=18 ) showed no statistically significant change at any visit . Changes in FT levels paralleled changes in TT levels in both groups . TTG group IIEF scores were significantly increased at month 3 ( P=0.01 ) , compared with a decline in placebo scores . No drug-related AEs occurred in the TTG group ; the placebo group had 2 AEs ( mild skin rash ) . In conclusion , TTG effectively restores serum TT and FT levels to a normal physiological range for hypogonadal men in Taiwan and improves sexual function ", "BACKGROUND Loss of muscle mass ( sarcopenia ) leads to frailty in older men . The decline in testosterone over the life span may contribute to this muscle loss . We studied the ability of oral testosterone to prevent muscle loss in older men over a 12-month period . METHODS A st and ard dose ( 80 mg twice daily ) of testosterone undecanoate or placebo was administered for 1 year to 76 healthy men aged 60 years or older . All men had a free testosterone index of 0.3 - 0.5 , which represents a value below the normal lower limit for young men ( 19 - 30 years ) , but remains within the overall normal male range . Measurements of body composition , muscle strength , hormones , and safety parameters were obtained at 0 , 6 , and 12 months . RESULTS Lean body mass increased ( p = .0001 ) and fat mass decreased ( p = .02 ) in the testosterone as compared with the placebo-treated group . There were no significant effects on muscle strength . There was a significant increase in hematocrit ( 0.02 % ) in the testosterone-treated group ( p = .03 ) . Plasma triglycerides , total cholesterol , and low-density lipoprotein cholesterol levels were similar in both groups , but there was a decrease in high-density lipoprotein cholesterol ( -0.1 mmol/L ) at 12 months in the testosterone group as compared to the placebo group ( p = 0.026 ) . There were no differences in prostate-specific antigen or systolic or diastolic blood pressure between the groups . CONCLUSION Oral testosterone administration to older relatively hypogonadal men results in an increase in muscle mass and a decrease in body fat", "There have not been studies assessing the effects of chronic testosterone cypionate ( TC ) therapy on circulating levels of testosterone ( T ) , estradiol ( E2 ) , free T , bioavailable T ( BAT ) , luteinizing hormone ( LH ) , and sexual function in impotent men with low T levels . This study was a double-blind crossover using 200 mg of TC or placebo given intramuscularly every 14 days for six injections and the other medication given for six doses . Blood was drawn before each injection . Mean concentrations of T , E2 , free T , and BAT were the same on TC or on placebo , but serum LH was significantly suppressed during intramuscular TC . With TC statistically significant improvements in libido and in potency were noted . Five of the men were able to have vaginal sex while taking TC . TC injections every 14 days do not appear to maintain increased T concentrations for 2 full weeks , and other dosage/injection schedules are being evaluated , but there were improvements in libido and potency", "Despite the widespread use of and rogen in the treatment of hypogonadal men , its efficacy in restoring sexual behavior to hypogonadal patients has not been established in appropriately controlled behavioral studies . Accordingly , testosterone enanthate or vehicle was injected once every 4 weeks i m in a double blind experiment . The subjects were six adult males , aged 32 - 65 yr , two with gonadal failure and four with secondary hypogonadism . Two doses of testosterone ( 100 and 400 mg ) were administered for approximately 5 months , with the treatments varied at r and om within and among subjects . Details of sexual activity and experience were followed by the use of daily logs . Frequencies of erections , including nocturnal erections and coitus , showed significant dose-related responses to and rogen treatment which closely followed the fluctuations in the circulating testosterone level . As indicated by the Profile of Mood States test , behavioral responses did not appear to be mediated by changes in mood . We concluded that the stimulatory effects of testosterone on sexual activity are rapid , reliable , and not due to a placebo effect . To maintain plasma testosterone and adequate sexual function within normal levels , even high doses of testosterone enanthate should be given no less frequency than once every 3 weeks", "Symptoms of male hypogonadism such as low libido and erectile dysfunction ( ED ) respond to testosterone ( T ) replacement . In hypogonadal men with major depressive disorder ( MDD ) , the extent to which T replacement alleviates sexual symptoms of hypogonadism is not known . We conducted 6 week double-blind placebo-controlled clinical trial in men with low and low-normal T levels ( i.e. , total T ≤ 350 ng/dl ) and MDD . Men were r and omized to receive weekly intramuscular injections of either T enanthate 200 mg or sesame-seed oil ( placebo ) . The primary outcome measure was self-reported sexual functioning . We r and omized 30 patients . The mean age was 52(SD ± 8) years , mean T level 262.5(SD ± 8) ng/dl , and mean baseline Hamilton Rating Scale for Depression ( HAM-D ) score 21(SD ± 8) . At baseline , sexual function was low , with the majority reporting having had normal erectile and orgasmic functioning 0–1 time in the preceding month . All patients who received T achieved normalization of their T levels . The HAM-D scores decreased significantly in both T and placebo groups , and there were no significant between-group differences : reduction in mean HAM-D score from baseline to endpoint was 10.1 in patients who received T and 10.5 in those who received placebo . Self-reported sexual functioning improved slightly in both groups ; a between-group difference was not detected . Both T replacement and placebo were associated with improvement in sexual function and mood , but differences between T and placebo were not distinguishable", "IMPORTANCE Testosterone use in older men is increasing , but its long-term effects on progression of atherosclerosis are unknown . OBJECTIVE To determine the effect of testosterone administration on sub clinical atherosclerosis progression in older men with low or low-normal testosterone levels . DESIGN , SETTING , AND PARTICIPANTS Testosterone 's Effects on Atherosclerosis Progression in Aging Men ( TEAAM ) was a placebo-controlled , double-blind , parallel-group r and omized trial involving 308 men 60 years or older with low or low-normal testosterone levels ( 100 - 400 ng/dL ; free testosterone Recruitment took place between September 2004 and February 2009 ; the last participant completed the study in May 2012 . INTERVENTIONS One hundred fifty-six participants were r and omized to receive 7.5 g of 1 % testosterone and 152 were r and omized to receive placebo gel packets daily for 3 years . The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES Co primary outcomes included common carotid artery intima-media thickness and coronary artery calcium ; secondary outcomes included sexual function and health-related quality of life . RESULTS Baseline characteristics were similar between groups : patients were a mean age of 67.6 years ; 42 % had hypertension ; 15 % , diabetes ; 15 % , cardiovascular disease ; and 27 % , obesity . The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group ( mean difference adjusted for age and trial site , 0.0002 mm/year ; 95 % CI , -0.003 to 0.003 , P = .89 ) . The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group ( adjusted mean difference , -10.8 Agatston units/year ; 95 % CI , -45.7 to 24.2 ; P = .54 ) . Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone . Sexual desire , erectile function , overall sexual function scores , partner intimacy , and health-related quality of life did not differ significantly between groups . Hematocrit and prostate-specific antigen levels increased more in testosterone group . CONCLUSIONS AND RELEVANCE Among older men with low or low-normal testosterone levels , testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life . Because this trial was only powered to evaluate atherosclerosis progression , these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00287586", "Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men . We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed , hypogonadal men . For this study , we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower . We r and omized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen . The primary outcome measure was the Hamilton Depression Rating Scale ( HDRS ) score . Secondary measures included the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impression Scale , and the Quality of Life Scale . Our primary analysis , using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures , failed to show a significant difference between groups ( mean [ 95 % confidence interval ] 6-week change in HDRS for testosterone vs placebo , −0.4 [ −2.6 to 1.8 ] ) . However , in one exploratory analysis of treatment responders , we found a possible trend in favor of testosterone on the HDRS . Our findings , combined with the conflicting data from earlier smaller studies , suggest that testosterone is not generally effective for depressed men . The possibility remains that testosterone might benefit a particular subgroup of depressed men , but if so , the characteristics of this subgroup would still need to be established", "CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women", "Testosterone replacement therapy ( TRT ) has been investigated in older men as a preventative treatment against Alzheimer 's disease and dementia . However , previous studies have been contradictory . We assessed TRT physiological effects in 44 older men ( aged 61 ± 7.7 years ) with subjective memory complaints using a double blind , r and omized , crossover , placebo-controlled study . Participants were r and omized into 2 groups , one group received transdermal testosterone ( 50 mg ) daily for 24 weeks , followed by a 4 week wash-out period , then 24 weeks of placebo ; the other group received the reverse treatment . Blood evaluation revealed significant increases in total testosterone , free ( calculated ) testosterone , dihydrotestosterone , and a decrease in luteinizing hormone levels ( p following TRT . Although there were significant increases in red blood cell counts , hemoglobin and prostate specific antigen levels following TRT , they remained within normal ranges . No significant differences in plasma amyloid beta , estradiol , sex hormone binding globulin , insulin levels , body fat percentage , or body mass index were detected . This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men on blood biomarkers linked to dementia risk . Our study suggests TRT is safe and well-tolerated in this Indonesian cohort , yet longitudinal studies with larger cohorts are needed to assess TRT further , and to establish whether TRT reduces dementia risk", "OBJECTIVE Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency . No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy ( TRT ) . We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone . RESEARCH DESIGN AND METHODS A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years . mortality rates were compared between total testosterone 10.4nmol/l ( 300ng/dl ; n=343 ) and testosterone 10.4nmol/l ( n=238 ) . the effect of TRT ( as per normal clinical practise : 85.9 % testosterone gel and 14.1 % intramuscular testosterone undecanoate ) was assessed retrospectively within the low testosterone group . RESULTS Mortality was increased in the low testosterone group ( 17.2 % ) compared with the normal testosterone group ( 9 % ; P=0.003 ) when controlled for covariates . In the Cox regression model , multivariate-adjusted hazard ratio ( HR ) for decreased survival was 2.02 ( P=0.009 , 95 % CI 1.2 - 3.4 ) . TRT ( mean duration 41.6±20.7 months ; n=64 ) was associated with a reduced mortality of 8.4 % compared with 19.2 % ( P=0.002 ) in the untreated group ( n=174 ) . The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 ( 95 % CI 1.3 - 3.9 , P=0.004 ) . CONCLUSIONS Low testosterone levels predict an increase in all-cause mortality during long-term follow-up . Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes", "AIMS Anabolic therapy with testosterone may be useful in the treatment of wasting associated with chronic heart failure but little is known about its cardiovascular actions . The aim of this study was to determine the acute haemodynamic effects of testosterone administration in men with heart failure . METHODS AND RESULTS Twelve men with stable chronic heart failure were enrolled in a double-blind , r and omised , placebo-controlled , cross-over trial . Subjects were given testosterone 60 mg or placebo via the buccal route and central haemodynamics were monitored over 6h , using a pulmonary flotation catheter . Subjects received the second treatment on day 2 and haemodynamic monitoring was repeated . Treatment was well tolerated . Compared with placebo , testosterone treatment result ed in a relative increase in cardiac output ( p systemic vascular resistance compared with baseline ( p serum bio-available testosterone . There was no significant change in any other haemodynamic parameter measured . CONCLUSIONS Administration of testosterone increases cardiac output acutely , apparently via reduction of left ventricular afterload", "Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow . Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease . However , the effects on myocardial perfusion are unknown . Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone . Twenty-two men ( mean age 57 ± 9 [ SD ] years ) were r and omly assigned to oral testosterone undecanoate ( TU ; 80 mg twice daily ) or placebo in a crossover study design . After each 8-week period , subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance , pulse-wave analysis , and endothelial function measurements using radial artery tonometry , blood sampling , anthropomorphic measurements , and quality -of-life assessment . Although no difference was found in global myocardial perfusion after TU compared with placebo , myocardium supplied by unobstructed coronary arteries showed increased perfusion ( 1.83 ± 0.9 vs 1.52 ± 0.65 ; p = 0.037 ) . TU decreased basal radial and aortic augmentation indexes ( p = 0.03 and p = 0.02 , respectively ) , indicating decreased arterial stiffness , but there was no effect on endothelial function . TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference , but had no effect on hemostatic factors , quality of life , and angina symptoms . In conclusion , oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries , in line with previous intracoronary findings . The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia", "The effects of and rogen withdrawal and replacement were investigated in six hypergonadotrophic and six hypogonadotrophic men with hypogonadism . A double blind cross‐over design was used comparing testosterone undecanoate ( T.U. , Organon International ) , 160 mg daily by mouth , with placebo . There was a significant effect of T.U. on all measures of sexual interest and behaviour . Sexual interest increased within the first week of T.U. administration , ejaculation usually returning within the second week . Behavioural responses were similar in the hyper‐ and hypogonadotrophic groups", "H igh and rogen levels in men have been regarded as a risk factor for coronary artery disease ( CAD ) . However , it has recently been demonstrated that supplements of and rogens inhibit atheroma formation in castrated male animals , suggesting that testosterone may be antiatherosclerotic . In men with angina pectoris , a significant inverse correlation was found between plasma testosterone levels and the extent of CAD , demonstrating that low testosterone levels could be a risk factor for CAD . Other reports suggest that testosterone replacement therapy in men with CAD has a beneficial effect on angina pectoris and exercise-induced ST-segment depression . Another study showed that testosterone enhanced endotheliumindependent coronary artery dilation and flow-mediated brachial arterial vasoreactivity in men with CAD . In this study , we assessed the effects of oral testosterone administration on brachial arterial vasoreactivity in men with CAD . • • • Thirty-five men ( aged 58 8 years ) with CAD were r and omized to placebo ( n 17 ) or treatment group ( n 18 ) . Demographics of the study group are summarized in Table 1 . Diagnostic criteria of CAD are a history of unstable and stable angina pectoris with angiographic evidence ( 50 % stenosis of lumen diameter ) . Exclusion criteria were inflammatory disease or malignancy , ejection fraction 45 % , clinical evidence of heart failure , and Q-wave myocardial infa rct ion within 3 months before the study . The treatment group completed oral administration of 160 mg of testosterone undecanoate ( And riol , N.V. Organon , Oss , The Netherl and s ) daily for 4 weeks followed by 80 mg testosterone undecanoate for 8 weeks , in addition to their current medication . Using high-resolution ultrasound , we assessed brachial arterial vasoreactivity to reactive hyperemia ( flow-mediated dilation ) and sublingual nitroglycerin ( nitroglycerin-mediated dilation ) at baseline and after 12 weeks of treatment . Patients taking nitrates discontinued therapy 24 hours before the study to avoid nitrate tolerance . A 10-MHz linear phased-array ultrasound transducer ( GE Vigmed Ultrasound , Horten , Norway ) was used to image the dominant arm brachial artery longitudinally 3 to 5 cm just above the antecubital fossa . All patients rested in the supine position for 10 minutes in a quiet room . After the depth and gain setting were optimized to identify the vessel wall , the brachial artery diameter was measured from the anterior to the posterior interface between the media and the adventitia and determined at end-diastole on B mode . Reactive hyperemia was induced by inflation and then deflation of a pneumatic cuff placed around the upper arm . The blood pressure cuff was inflated to 250 mm Hg for 5 minutes . After release of the cuff , brachial artery diameter was measured within the first 15 seconds of reactive hyperemia . The brachial artery was allowed to return to the baseline level until 10 minutes after cuff release . Then , a further baseline brachial artery diameter was obtained . Nitroglycerin , 0.6 mg , was then given sublingually , and the brachial artery diameter was measured for the ensuing 3 minutes . The percent change in diameter caused by reactive hyperemia was calculated by dividing the difference from baseline end-diastolic diameter by the baseline value . The percent change in diameter caused by nitroglycerin administration was also calculated in the same way . Blood pressure and heart rate were measured before the examination . All data were calculated as an average of 4 consecutive cardiac cycles . Early morning blood sampling for fasting lipid profiles was performed and plasma-free testosterone levels were obtained immediately before ultrasound imaging and 12 weeks later . A st and ard radioimmunoassay method was used for analysis ( DSL-4900 kit , Diagnostic System Laboratory Inc. , Houston , Texas ) . All descriptive data are presented as mean SD and analyzed using SPSS for Windows 9.0 ( SPSS Inc. , Chicago , Illinois ) From the Cardiology Division , Yonsei Cardiovascular Center and Cardiovascular Research Institute , College of Medicine , Seoul ; and Department of Food and Nutrition , College of Ecology , Yonsei University , Seoul , South Korea . Dr. Jang ’s address is : Cardiology Division , Yonsei Cardiovascular Center , Yonsei University College of Medicine , 134 , Shinchon-Dong , Seodaemun-Gu , Seoul 120 - 752 , South Korea . E-mail : [email protected] . Manuscript received August 10 , 2001 ; revised manuscript received and accepted December 10 , 2001 . TABLE 1 Clinical Characteristics of Study", "OBJECTIVE The objective of the study was to assess the effect of T treatment on constitutional and sexual symptoms in men with type 2 diabetes ( T2D ) . DESIGN This was a r and omized double-blind , parallel , placebo-controlled trial . SETTING The study was conducted at a tertiary referral center . PATIENTS Men aged 35 - 70 years with T2D , a hemoglobin A1c less than 8.5 % , and a total T level less than 12.0 nmol/L ( 346 ng/dL ) with mild to moderate aging male symptoms and erectile dysfunction . INTERVENTION Eighty-eight participants were r and omly assigned to 40 weeks of i m T undecanoate ( n = 45 ) or matching placebo ( n = 43 ) . MAIN OUTCOME MEASURES Constitutional symptoms using the aging male symptoms ( AMS ) score , sexual desire ( question 17 AMS score ) , and erectile function ( International Index of Erectile Function-5 ) . RESULTS T treatment did not substantially improve aging male symptoms [ mean adjusted difference ( MAD ) in change over 40 weeks across the T and placebo groups in AMS total score , -0.9 ( 95 % confidence interval [ CI ] -4.1 , 2.2 ) , P = .67 ] or sexual desire [ MAD in question 17 AMS , -0.3 ( 95 % CI -0.8 , 0.2 ) , P = .17 ] . Although compared with placebo , erectile function in men assigned to T was reduced [ MAD in International Index of Erectile Function abridged version 5 , -2.0 ( 95 % CI -3.4 , -0.6 ) , P International Index of Erectile Function abridged version 5 scores if both groups were analyzed separately . At baseline , symptoms were worse in men with depression and microvascular complications but did not correlate with T levels . CONCLUSIONS In this trial , T treatment did not substantially improve constitutional or sexual symptoms in obese , aging men with T2D with mild to moderate symptoms and modest reduction in T levels typical for the vast majority of such men", "OBJECTIVE Testosterone deficiency is associated with significant morbidity , and and rogen replacement in overt hypogonadism is clearly beneficial . However , there are few data concerning the response to therapy in young men with mild testosterone deficiency", "We examined the effects of GH and /or testosterone ( T ) administration on body composition , performance , mood , sexual function , bone turnover , and muscle-gene expression in healthy older men . Ten men [ mean ( SEM ) age , 68 ( 2.5 ) yr ; height , 171.5 ( 2.4 ) cm ; and weight , 80 ( 3.0 ) kg ] completed each of the following 1-month , double-blind interventions after a baseline ( B ) study in r and omized order with an intervening 3-month washout : transdermal T patch ( 5.0 mg/daily ) ; recombinant human GH ( 6.25 micro g/kg sc daily ) ; and combined hormones ( GHT ) . ANOVA with repeated measures was used to evaluate interventional effects . Integrated serum GH concentrations [ mean ( SEM ) ] were elevated comparably by GH and GHT : [ B = 363 ( 55 ) , GH = 1107 ( 120 ) , T = 459 ( 131 ) , and GHT = 1189 ( 46 ) micro g/liter.min ; P Serum IGF-I concentrations also increased commensurately after GH and GHT : [ B = 168 ( 14 ) , GH = 285 ( 16 ) , T = 192 ( 25 ) , and GHT = 294 ( 25 ) micro g/liter ; P GHT administration increased total estradiol : [ B = 110 ( 20 ) , GH = 106 ( 13 ) , T = 129 ( 13 ) , and GHT = 153 ( 17 ) pmol/liter ; P T and GHT elevated free T : [ B = 12 ( 2.1 ) , GH = 11 ( 1.5 ) , T = 22 ( 2.8 ) , and GHT = 24 ( 2.5 ) pg/ml ; P strength , flexibility , percentage body fat , or sexual function and mood . However , fat-free mass increased under combined GHT exposure : [ B = 55 ( 1.3 ) , GH = 56 ( 1.1 ) , T = 55 ( 1.5 ) , GHT = 57 ( 1.7 ) kg ; P Balance improved in response to GH intervention ( P T and GHT interventions [ B = 6.6 ( 0.3 ) , GH = 6.2 ( 0.7 ) , T = 5.9 ( 0.3 ) , GHT = 5.5 ( 0.3 ) sec ; P = 0.04 ] and stair climb time for all three interventions [ B = 32.2 ( 1.4 ) , GH = 29.8 ( 1.2 ) , T = 30.5 ( 1.4 ) , and GHT = 29.9 ( 1.2 ) sec ( P = 0.0034 ) , wherein the effects of GH , T , and GHT were different from that of B ] . Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration ( P Myostatin and and rogen receptor gene expression were not affected . Serum osteocalcin increased in response to the GH and GHT interventions : [ B = 4.8 ( 0.52 ) , GH = 5.7 ( 0.54 ) , T = 4.7 ( 0.33 ) , and GHT = 5.5 ( 0.39 ) ; P adverse events during 30 patient-months of intervention . We conclude that 1 month of GH and /or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression", "The aim of this study was to assess the effect of a low-dose testosterone on body composition and pulmonary function , as well as on quality of life , sexuality , and psychological symptoms in patients with chronic obstructive pulmonary disease ( COPD ) . Twenty-nine men with moderate to severe COPD were allocated to receive either 250 mg of testosterone or placebo intra-muscularly , every fourth week , during the 26 weeks study period . Fat-free mass increased in the treatment group ( P Fat mass decreased in the treatment group ( P better erectile function was reported in the treatment group at the final visit ( P overall sexual quality of life was significantly better in the treatment group after 12 weeks ( P pulmonary function was found . In conclusion , administration of a low-dose testosterone to men with COPD for 26 weeks was associated with improvement of body composition , better erectile function and sexual quality of life . Furthermore , there were no clinical or biochemical side effects", "We investigated whether the and rogen type or application mode or testosterone ( T ) serum levels influence serum lipids and lipoprotein levels differentially in 55 hypogonadal men r and omly assigned to the following treatment groups : mesterolone 100 mg orally daily ( [ MES ] n = 12 ) , testosterone undecanoate 160 mg orally daily ( [ TU ] n = 13 ) , testosterone enanthate 250 mg intramuscularly every 21 days ( [ TE ] n = 15 ) , or a single subcutaneous implantation of crystalline T 1,200 mg ( [ TPEL ] n = 15 ) . The dosages were based on st and ard treatment regimens . Previous and rogen substitution was suspended for at least 3 months . Only metabolically healthy men with serum T less than 3.6 nmol/L and total cholesterol ( TC ) and triglyceride ( TG ) less than 200 mg/dL were included . After a screening period of 2 weeks , the study medication was taken from days 0 to 189 , with follow-up visits on days 246 and 300 . Before substitution , all men were clearly hypogonadal , with mean serum T less than 3 nmol/L in all groups . And rogen substitution led to no significant increase of serum T in the MES group , subnormal T in the TU group ( 5.7 + /- 0.3 nmol/L ) , normal T in the TE group ( 13.5 + /- 0.7 nmol/L ) , and high-normal T in the TPEL group ( 23.2 + /- 1.1 nmol/L ) . 5 alpha-Dihydrotestosterone significantly increased in all treatment groups compared with baseline . Compared with presubstitution levels , a significant increase of TC was observed in all treatment groups ( TU , 14.4 % + /- 3.0 % ; MES , 18.8 % + /- 2.5 % ; TE , 20.4 % + /- 3.0 % ; TPEL , 20.2 % + /- 2.6 % ) . Low-density lipoprotein cholesterol ( LDL-C ) also increased significantly by 34.3 % + /- 5.5 % ( TU ) , 46.4 % + /- 4.1 % ( MES ) , 65.2 % + /- 5.7 % ( TE ) , and 47.5 % + /- 4.3 % ( TPEL ) . High-density lipoprotein cholesterol ( HDL-C ) showed a significant decrease by -30.9 % + /- 2.8 % ( TU ) , -34.9 % + /- 2.5 % ( MES ) , -35.7 % + /- 2.6 % ( TE ) , and -32.5 % + /- 3.5 % ( TPEL ) . Serum TG significantly increased by 37.3 % + /- 11.3 % ( TU ) , 46.4 % + /- 10.3 % ( MES ) , 29.4 % + /- 6.5 % ( TE ) , and 22.9 % + /- 6.7 % ( TPEL ) . TU caused a smaller increase of TC than TE and TPEL , whereas the parenteral treatment modes showed a lower increase of TG . There was no correlation between serum T and lipid concentrations . Despite the return of serum T to pretreatment levels , serum lipid and lipoprotein levels did not return to baseline during follow-up evaluation . In summary , and rogen substitution in hypogonadal men increases TC , LDL-C , and TG and decreases HDL-C independently of the and rogen type and application made and the serum and rogen levels achieved . Due to the extended washout period for previous and rogen medication and the exclusion of men with preexisting hyperlipidemia , this investigation demonstrates more clearly than previous studies the impact of and rogen effects on serum lipids and lipoproteins . It is concluded that preexisting low serum and rogens induce a \" male-type \" serum lipid profile , and increasing serum and rogens further within the male normal range does not exert any additional effects . The threshold appears to be above the normal female and rogen serum levels and far below the lower limit of normal serum T levels in adult men . These findings may have considerable implication s for the use of and rogens as a male contraceptive and for and rogen therapy in elderly men ", "PURPOSE Weight loss is a strong predictor of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients . Men with acquired immunodeficiency syndrome ( AIDS ) lose body cell mass . Hypogonadism is also common . This study tested the efficacy of a testosterone transscrotal patch ( 6 mg/day ) in improving body cell mass and treating hypogonadism in these patients . SUBJECTS AND METHODS This multicenter , r and omized , double-blinded , placebo-controlled trial was conducted from August 1995 to October 1996 in 133 men , 18 years of age and older , who had AIDS , 5 % to 20 % weight loss , and either a low morning serum total testosterone level ( Outcomes included weight , body cell mass as measured using bioelectrical impedance analysis , quality of life , and morning measurements of serum testosterone and dihydrotestosterone levels , lymphocyte subsets , and HIV quantification . RESULTS There were no significant differences in baseline weight , CD4 cell counts , or HIV serum viral quantification between treatment arms . Morning total and free testosterone levels increased in those treated with testosterone , but not with placebo . Following 12 weeks of treatment there were no differences ( testosterone-placebo ) in mean weight change ( -0.3 kg [ 95 % confidence interval ( CI ) : -1.4 to 0.8 ] ) or body cell mass ( -0.2 kg [ 95 % CI : -1.0 to 0.6 ] ) in the two groups . There were also no changes in quality of life in either group . CONCLUSION Hypogonadal men with AIDS and weight loss can achieve adequate morning serum sex hormone levels using a transscrotal testosterone patch . However , this system of replacement does not improve weight , body cell mass , or quality of life", "BACKGROUND Dehydroepi and rosterone ( DHEA ) and testosterone are widely promoted as antiaging supplements , but the long-term benefits , as compared with potential harm , are unknown . METHODS We performed a 2-year , placebo-controlled , r and omized , double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA . Among the men , 29 received DHEA , 27 received testosterone , and 31 received placebo . Among the women , 27 received DHEA and 30 received placebo . Outcome measures included physical performance , body composition , bone mineral density ( BMD ) , glucose tolerance , and quality of life . RESULTS As compared with the change from baseline to 24 months in the placebo group , subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 microg per milliliter ( 9.2 micromol per liter ) in men and by 3.8 microg per milliliter ( 10.3 micromol per liter ) in women . Among men who received testosterone , the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter ( 1.1 nmol per liter ) , as compared with the change in the placebo group . A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements . Neither hormone altered the peak volume of oxygen consumed per minute , muscle strength , or insulin sensitivity . Men who received testosterone had a slight increase in fat-free mass , and men in both treatment groups had an increase in BMD at the femoral neck . Women who received DHEA had an increase in BMD at the ultradistal radius . Neither treatment improved the quality of life or had major adverse effects . CONCLUSIONS Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition , physical performance , insulin sensitivity , or quality of life . ( Clinical Trials.gov number , NCT00254371 [ Clinical Trials.gov ] . )", "OBJECTIVE The objective of this study was to examine the relationship between anabolic-- and rogenic steroids and lipoprotein levels in men receiving weekly injections of gradually escalating doses of up to 600 mg/week of testosterone cypionate . DESIGN The design was a placebo-controlled , double-blind , 24-week cross-over design in which subjects were r and omized to one of two treatment sequences : ( a ) weekly testosterone cypionate injections for 6 weeks , no treatment for 6 weeks , weekly placebo injections for 6 weeks , and then again no treatment for 6 weeks ; or ( b ) placebo , no treatment , testosterone , and then no treatment , with each interval also lasting 6 weeks as in the first sequence . SETTING The setting was a private hospital . PARTICIPANTS Participants were normal male volunteers . INTERVENTIONS Testosterone cypionate injections were given in gradually increasing doses of 150 mg/week for 2 weeks , 300 mg/week for 2 weeks , and 600 mg/week for 2 weeks . Eight subjects received testosterone injections during the first injection phase and placebo during the second injection phase , and the remaining eight subjects received placebo first and testosterone second . RESULTS We found a 21 % depression of high-density lipoprotein cholesterol ( HDL-C ) levels following the first 300-mg testosterone dose . This depression remained unchanged after the two 600-mg doses . In contrast , we did not find any changes in low-density lipoprotein or total cholesterol levels at any of the time points studied . Subjects ' total cholesterol/HDL-C ratios were significantly elevated during testosterone administration and even 4 weeks following the last injection . CONCLUSION Our findings suggest that testosterone cypionate adversely affects cholesterol fractions , that this effect reaches its full magnitude even at very modestly supraphysiologic doses , and that this effect persists for several weeks after discontinuation of the drug", "CONTEXT Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength . The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown . OBJECTIVE To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss . DESIGN AND SETTING Placebo-controlled , double-blind , r and omized clinical trial conducted from September 1995 to July 1998 at a general clinical research center . PARTICIPANTS Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L ( 349 ng/dL ) and weight loss of 5 % or more in the previous 6 months , 49 of whom completed the study . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : placebo , no exercise ( n = 14 ) ; testosterone enanthate ( 100 mg/wk intramuscularly ) , no exercise ( n = 17 ) ; placebo and exercise ( n = 15 ) ; or testosterone and exercise ( n = 15 ) . Treatment duration was 16 weeks . MAIN OUTCOME MEASURES Changes in muscle strength , body weight , thigh muscle volume , and lean body mass compared among the 4 treatment groups . RESULTS Body weight increased significantly by 2.6 kg ( P testosterone alone and by 2.2 kg ( P = .02 ) in men who exercised alone but did not change in men receiving placebo alone ( -0.5 kg ; P = .55 ) or testosterone and exercise ( 0.7 kg ; P = .08 ) . Men treated with testosterone alone , exercise alone , or both experienced significant increases in maximum voluntary muscle strength in leg press ( range , 22%-30 % ) , leg curls ( range , 18%-36 % ) , bench press ( range , 19%-33 % ) , and latissimus pulls ( range , 17%-33 % ) . Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group . There was a greater increase in thigh muscle volume in men receiving testosterone alone ( mean change , 40 cm3 ; P placebo alone ( 5 cm3 ; P = .70 ) . Average lean body mass increased by 2.3 kg ( P = .004 ) and 2.6 kg ( P testosterone alone or testosterone and exercise but did not change in men receiving placebo alone ( 0.9 kg ; P = .21 ) . Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo . CONCLUSION Our data suggest that testosterone and resistance exercise promote gains in body weight , muscle mass , muscle strength , and lean body mass in HIV-infected men with weight loss and low testosterone levels . Testosterone and exercise together did not produce greater gains than either intervention alone", "OBJECTIVES To determine whether testosterone supplementation improves rehabilitation outcomes in ill older men . DESIGN A r and omized , placebo-controlled , double-blind study . SETTING A Geriatric Evaluation and Management ( GEM ) unit based at a university- affiliated Veterans Affairs Medical Center . PARTICIPANTS Fifteen men aged 65 to 90 years admitted to the GEM for rehabilitation . INTERVENTION Subjects were r and omized to receive weekly intramuscular injections with testosterone enanthate 100 mg or placebo . MEASUREMENTS Task-specific performance using the Functional Independence Measure ( FIM ) and grip strength was measured at the onset of the study and at the time of discharge from the GEM . RESULTS At baseline , FIM scores were similar between the placebo and the testosterone group ( 73.7 vs 70.7 , P = .637 ) , as was grip strength ( 49.7 vs 55.3 pounds , P = .555 ) . At discharge from the GEM , testosterone-treated patients had improved FIM scores compared with baseline ( 93.6 vs 70.7 ; P = .012 ) and grip strength ( 68.7 vs 55.3 pounds ; P = .033 ) . In the placebo group there was no significant improvement of FIM scores compared with baseline ( 78.0 versus 73.7 ; P = .686 ) or of grip strength ( 48.9 vs 49.7 pounds ; P = .686 ) . CONCLUSIONS Testosterone supplementation may improve rehabilitation outcomes in ill older men", "Testosterone replacement is the most effective treatment for sexual dysfunction in hypogonadal men . Comorbid depression and antidepressant side effects may reduce its influence . The authors conducted a 6-week , double-blind , placebo-controlled clinical trial of testosterone gel versus placebo gel in men with major depressive disorder who were currently taking a serotonergic antidepressant and exhibited low or low-normal testosterone level . A total of 100 men were enrolled at 2 study sites ( Boston , Massachusetts , USA , and Tel Aviv , Israel ) . The effects of testosterone augmentation on sexual functioning were determined using domain scores on the International Index of Erectile Function ( IIEF ) . Complete pre- and posttrial IIEF data were available for 63 subjects . Men r and omized to testosterone ( n = 31 ) and placebo ( n = 32 ) were similar in age , baseline testosterone levels , and baseline IIEF scores . At study termination , men r and omized to placebo showed virtually no change from baseline in mean ( 95 % CI ) IIEF score ( −0.7 [ −6.5 , 5.2 ] ) , whereas those receiving testosterone exhibited a substantial increase ( 15.8 [ 8.5 , 23.1 ] ) . The estimated mean difference between groups was 16.8 [ 7.5 , 26.1 ] ; p = .001 by linear regression with adjustment for age and study site . There were also significant between-group differences in each of the 5 IIEF subscales , as well as on the single question involving ejaculatory ability ( p ≤ .03 in all cases ) . Effect sizes in these comparisons remained little changed , and generally remained statistically significant , when we further adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale . It is notable that the subgroup of men with the highest baseline testosterone levels showed virtually the same improvement as those with lower levels , suggesting that the observed improvement was unlikely to be due simply to correction of hypogonadism alone . In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants , treatment with exogenous testosterone was associated with a significant improvement in sexual function , particularly including ejaculatory ability", "Background : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression", "BACKGROUND Studies on the effect of estrogen on atherosclerotic coronary artery disease ( CAD ) risk in women have produced conflicting results . Similar confusion , but fewer data , exists on the effect of testosterone on CAD risk in men . METHODS We used 99mTc sestamibi single-photon emission computed tomography ( SPECT ) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men ( mean age , 69.1 + /- 6.4 years ) with provocable myocardial ischemia on st and ard medical therapy . Patients performed 3 exercise ( n = 18 ) or adenosine ( n = 16 ) stress tests during the infusion of placebo or 2 doses of testosterone design ed to increase testosterone 2 or 6 times baseline . RESULTS Serum testosterone increased 137 + /- 58 % and 488 + /- 113 % , and estradiol levels increased 27 + /- 46 % and 76 + /- 57 % , ( P testosterone infusions . There were no differences among the placebo or testosterone groups in peak heart rate , systolic blood pressure , maximal rate pressure product , perfusion imaging scores , or the onset of ST-segment depression . CONCLUSIONS Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD", "The basis was established for a rational sex hormone therapy with the isolation of the estrogenicl 2 s and and rogenic hormones.3 It has been demonstrated by animal experiments that a basic effect of the sex hormones is hyperemization of the whole organism.4 4 When this observation was confirmed with regards to the skin in the 1930 ’s in patients treated for well defined gonad insufficiency , the possibility then existed of treating patients with diseases of the circulatory system with sex hormones ", "The efficacy and safety of and rogen supplementation in older men remains controversial . Despite biochemical evidence of partial and rogen deficiency in older men , controlled studies using T demonstrate equivocal benefits . Furthermore , the importance of aromatization and 5alpha reduction in and rogen actions among older men remains unclear . Dihydrotestosterone is the highest potency natural and rogen with the additional features that it is neither aromatizable nor susceptible to potency amplification by 5alpha reduction . Therefore , the effects of dihydrotestosterone may differ from those of T in older men . This study evaluated the efficacy and safety of 3 months treatment with transdermal dihydrotestosterone gel on muscle strength , mobility , and quality of life in ambulant , community-dwelling men aged 60 yr or older . Eligible men ( plasma T were r and omized to undergo daily dermal application of 70 mg dihydrotestosterone gel ( n = 18 ) or vehicle ( n = 19 ) and were studied before , monthly during , and 1 month after treatment . Among 33 ( 17 dihydrotestosterone , 16 placebo ) men completing the study with a high degree of compliance , dihydrotestosterone had significant effects on circulating hormones ( increased dihydrotestosterone ; decreased total and free testosterone , LH , and FSH ; unchanged SHBG and estradiol ) , lipid profiles ( decreased total and low-density lipoprotein cholesterols ; unchanged high-density lipoprotein cholesterol and triglycerides ) , hematopoiesis ( increased hemoglobin , hematocrit , and red cell counts ) , and body composition ( decreased skinfold thickness and fat mass ; unchanged lean mass and waist to hip ratio ) . Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee but not in knee extension or shoulder contraction , nor was there any significant change in gait , balance , or mobility tests , in cognitive function , or in quality of life scales . Dihydrotestosterone treatment had no adverse effects on prostate ( unchanged prostate volumes and prostate-specific antigen ) and cardiovascular ( no adverse change in vascular reactivity or lipids ) safety markers . We conclude that 3 months treatment with transdermal dihydrotestosterone gel demonstrates expected and rogenic effects , short-term safety , and limited improvement in lower limb muscle strength but no change in physical functioning or cognitive function", "Mid-life onset male dysthymic disorder ( DD ) seems to be a distinct clinical condition with limited therapeutic options . Testosterone replacement is mood-enhancing and has been proposed as an antidepressant therapy , though this strategy has received limited systematic study . We therefore conducted a six-week double-blind placebo-controlled clinical trial in 23 men with DD and with low or low-normal testosterone ( T ) level ( i.e , screening total serum testosterone to receive intramuscular injections of 200 mg of testosterone cypionate or placebo every 10 days . The primary outcome measures were the Clinical Global Impression ( CGI ) improvement score and the 21-item Hamilton Depression Rating Scale ( HDRS ) score . Twenty-three patients were r and omized . The mean ( SD ) age of the enrolled patients was 50.6 ( 7.0 ) years and that of total testosterone level was 339 ( 93 ) ng/dL. The median duration of the current dysthymic episode was 3.6 ( 2.3 ) years , and the mean ( SD ) HDRS was 14.0 ( 2.9 ) . After the intervention , the mean HDRS score decreased significantly more in the testosterone group ( 7.46 [ 4.56 ] ) than in the placebo group ( 1.8 [ 4.13 ] , t21 = −3.07 , P = 0.006 ) . Remission , defined as a CGI improvement score of 1 or 2 and a final HDRS score lower than 8 , was achieved by 7 ( 53.8 % ) of 13 in the testosterone group and 1 ( 10 % ) of 10 in the placebo group ( P = 0.03 ) . Testosterone replacement may be an effective antidepressant strategy for late-onset male dysthymia", "Although decline in sexual function is a common reason for ageing men to seek advice regarding testosterone therapy , placebo-controlled trial data have been unable to show a consistent , beneficial role for testosterone . The objective of this study was to determine the effect of testosterone therapy on sexual function in non-obese ageing men with symptoms of and rogen deficiency and low – normal serum testosterone levels . A total of 60 men aged 55 years or older in good general health with total testosterone ( TT ) levels transdermal testosterone patches or placebo for 12 months . Sexual function was assessed using the International Index of Erectile Function at weeks 0 , 26 and 52 . In men receiving testosterone TT levels increased by 30 % ( P=0.01 ) and luteinizing hormone decreased by 50 % ( P improved sexual desire ( P=0.04 ) ; however other parameters of sexual function including erectile function were unaffected by the treatment . Ageing men in good general health and with symptoms of and rogen deficiency and low – normal serum testosterone levels receiving 12 months of transdermal testosterone therapy experienced , relative to placebo , improved sexual desire but no effect on other parameters of sexual function ", "OBJECTIVES This study investigated the effect of a 12-week long-acting testosterone administration on maximal exercise capacity , ventilatory efficiency , muscle strength , insulin resistance , and baroreflex sensitivity ( BRS ) in elderly patients with chronic heart failure ( CHF ) . BACKGROUND CHF is characterized by a metabolic shift favoring catabolism and impairment in skeletal muscle bulk and function that could be involved in the pathophysiology of heart failure . METHODS Seventy elderly patients with stable CHF-median age 70 years , ejection fraction 31.8 + /- 7%-were r and omly assigned to receive testosterone ( n = 35 , intramuscular injection every 6 weeks ) or placebo ( n = 35 ) , both on top of optimal medical therapy . At baseline and at the end of the study , all patients underwent echocardiogram , cardiopulmonary exercise test , 6-min walk test ( 6MWT ) , quadriceps maximal voluntary contraction ( MVC ) , and isokinetic strength ( peak torque ) and BRS assessment ( sequences technique ) . RESULTS Baseline peak oxygen consumption ( VO(2 ) ) and quadriceps isometric strength showed a direct relation with serum testosterone concentration . Peak VO(2 ) significantly improved in testosterone but was unchanged in placebo . Insulin sensitivity was significantly improved in testosterone . The MVC and peak torque significantly increased in testosterone but not in placebo . The BRS significantly improved in testosterone but not in placebo . Increase in testosterone levels was significantly related to improvement in peak VO(2 ) and MVC . There were no significant changes in left ventricular function either in testosterone or placebo . CONCLUSIONS These results suggest that long-acting testosterone therapy improves exercise capacity , muscle strength , glucose metabolism , and BRS in men with moderately severe CHF . Testosterone benefits seem to be mediated by metabolic and peripheral effects", "OBJECTIVES To investigate the effects of testosterone supplementation on bone , body composition , muscle , physical function , and safety in older men . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING A major medical institution . PARTICIPANTS One hundred thirty-one men ( mean age 77.1 + /- 7.6 ) with low testosterone , history of fracture , or bone mineral density ( BMD ) T-score less than -2.0 and frailty . INTERVENTION Participants received 5 mg/d of testosterone or placebo for 12 to 24 months ; all received calcium ( 1500 mg/d diet and supplement ) and cholecalciferol ( 1,000 IU/d ) . MEASUREMENTS BMD of hip , lumbar spine , and mid-radius ; body composition ; sex hormones , calcium-regulating hormones ; bone turnover markers ; strength ; physical performance ; and safety parameters . RESULTS Ninety-nine men ( 75.6 % ) completed 12 months , and 62 ( 47.3 % ) completed end therapy ( mean 23 months ; range 16 - 24 months for 62 who completed therapy ) . Study adherence was 54 % , with 40 % of subjects maintaining 70 % or greater adherence . Testosterone and bioavailable testosterone levels at 12 months were 583 ng/dL and 157 ng/dL , respectively , in the treatment group . BMD on testosterone increased 1.4 % at the femoral neck and 3.2 % at the lumbar spine ( P=.005 ) and decreased 1.3 % at the mid-radius ( P lean mass and a decrease in fat mass in the testosterone group but no differences in strength or physical performance . There were no differences in safety parameters . CONCLUSION Older , frail men receiving testosterone replacement increased testosterone levels and had favorable changes in body composition , modest changes in axial BMD , and no substantial changes in physical function", "OBJECTIVE To investigate the effects of oral testosterone undecanoate ( TU ) on symptoms associated with late-onset hypogonadism ( LOH ) . Design Multicenter , r and omized , double-blind , placebo-controlled . METHODS The study was performed in 14 study centers in seven European countries . Men > or = 50 years ( n=322 ) with symptoms of hypogonadism and testosterone deficiency ( calculated free testosterone and treated for 12 months with placebo or oral TU 80 , 160 or 240 mg/day . Primary outcome was the total score on the Aging Males ' Symptoms ( AMS ) rating scale after six months of treatment . RESULTS Treatment of mild-to-moderate LOH symptoms in subjects with borderline hypogonadism with oral TU result ed in an improved total AMS score at month 6 , but differences between groups were not statistically significant . There was greater improvement in subjects when compared with subjects > or = 60 years ( P=0.001 ) , but baseline testosterone level had no influence on treatment response . The AMS sexual symptoms domain improved with oral TU 160 mg/day at months 6 ( P=0.008 ) and 12 ( P=0.012 ) compared with placebo , but not with 80 and 240 mg/day . Treatment was well-tolerated and there were no between-group differences in adverse events or drop-out rates . CONCLUSIONS In one of the largest placebo-controlled studies of testosterone therapy in LOH , oral TU did not improve total AMS score in subjects with mild-to-moderate symptoms compared with placebo , except the sexual symptom sub-domain where a modest improvement was reported with oral TU 160 mg/day", "BACKGROUND Erectile dysfunction and low testosterone levels frequently occur together . OBJECTIVE To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels . DESIGN R and omized , double-blind , parallel , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00512707 ) SETTING Outpatient academic research center . PARTICIPANTS Men aged 40 to 70 years with scores of 25 or less for the erectile function domain ( EFD ) of the International Index of Erectile Function , total testosterone levels less than 11.45 nmol/L ( free testosterone levels less than 173.35 pmol/L ( INTERVENTION Sildenafil dose was optimized , and 140 participants were then r and omly assigned to 14 weeks of daily transdermal gel that contained 10-g testosterone for 70 participants and placebo for the remaining 70 participants . All participants were included in the primary analysis , although 10 in the testosterone group and 12 in the placebo group did not complete the study . RESULTS At baseline , the 2 groups had similar EFD scores . Administration of sildenafil alone was associated with a substantial increase in EFD score ( mean , 7.7 [ 95 % CI , 6.5 to 8.8 ] ) , but change in EFD score after r and omization did not differ between the groups ( difference , 2.2 [ CI , -0.8 to 5.1 ] ; P = 0.150 ) . The findings were similar for other domains of sexual function in younger men , more obese men , and men with lower baseline testosterone levels or an inadequate response to sildenafil alone . Frequency of adverse events was similar for testosterone and placebo groups . LIMITATION Whether testosterone could improve erectile function without sildenafil was not studied . CONCLUSION Sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with erectile dysfunction and low testosterone levels . PRIMARY FUNDING SOURCE National Institute of Child Health and Human Development" ]	41183c0e-06ff-11f0-808a-c43d1ab1c353
PURPOSE OF REVIEW To underst and the basis for current recommendations for vitamin D supplementation in childhood and the differences between the recommendations published by major expert committees , using the Medline engine of the US National Library of Medicine and the National Institutes of Health . RECENT FINDINGS Recent recommendations published by major national expert committees are essentially based on expert opinion ( a relatively low level of evidence ) . R and omized controlled trials are very few , and there are no systematic review s or meta-analyses on the topic . Most trials have examined the question of whether a specific daily vitamin D dose is capable or not to prevent rickets ( by study ing surrogate markers of rickets ) . There are no trials that have systematic ally attempted to determine the upper limit of daily vitamin D dose beyond which its toxic effects may appear . Whether or not outcomes such as osteoporosis ( or low bone mass ) and specific types of cancer may be prevented by ' generous ' vitamin D supplementation is unclear and mostly based on indirect epidemiologic data not clearly substantiated by r and omized controlled trials SUMMARY The dose of daily vitamin D supplements needed to prevent rickets is probably much lower than that recommended by most expert committees . Whether higher doses of daily vitamin D supplements may or may not prevent other poor outcomes such as adult osteoporosis or specific types of cancer is not yet known	[ "BACKGROUND The fortification of milk and infant formula with vitamin D has had an important role in eliminating rickets in children and osteomalacia in adults . A recent outbreak of vitamin D intoxication caused by drinking milk fortified with excess vitamin D has led to questions about the level of vitamin D in milk from other producers . METHODS We used high-performance liquid chromatography to measure vitamin D in sample s of 13 br and s of milk with various fat contents and 5 br and s of infant formula purchased at r and om from local supermarkets in five Eastern states . RESULTS Only 12 ( 29 percent ) of the 42 sample s of the 13 br and s of milk and none of the 10 sample s of the 5 br and s of infant formula contained 80 to 120 percent of the amount of vitamin D stated on the label . Twenty-six of the 42 milk sample s ( 62 percent ) contained less than 80 percent of the amount cl aim ed on the label . No vitamin D was detected in 3 of the 14 sample s of skim milk tested ( lower limit of assay , 4.7 IU per quart [ 5.0 IU per liter ] ) . One milk sample labeled as containing vitamin D2 ( ergocalciferol ) contained vitamin D3 ( cholecalciferol ) . Seven of the 10 sample s of infant formula contained more than 200 percent of the amount stated on the label ; the sample with the highest concentration contained 419 percent of the stated amount . None of the sample s of infant formula contained less than the amount stated . CONCLUSIONS Milk and infant-formula preparations rarely contain the amount of vitamin D stated on the label and may be either underfortified or overfortified . Since both underfortification and overfortification are hazardous , better monitoring of the fortification process is needed", "BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170", "The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial design ed to determine the effects of a high-fiber , high-fruit and vegetable , low-fat diet on the recurrence of adenomatous polyps in the large bowel . Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits . Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants . We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group , age , gender , nonsteroidal anti-inflammatory drug use , total energy intake , and the interaction of gender and intervention group . Vitamin D models were also adjusted for the location of the clinic site . Dietary variables were adjusted for total energy intake via the residual method . There were no overall significant associations between adenoma recurrence and dietary calcium intake [ odds ratio ( OR ) for the 5th compared with the lowest quintile = 0.91 ; 95 % CI = 0.67 - 1.23 ; P-trend = 0.68 ] , total calcium intake ( OR = 0.86 ; 95 % CI = 0.62 - 1.18 ; P-trend = 0.20 ) , or dietary vitamin D intake ( OR = 0.93 ; 95 % CI = 0.69 - 1.25 ; P-trend = 0.43 ) averaged over follow-up . Total vitamin D intake was weakly inversely associated with adenoma recurrence ( OR = 0.84 ; 95 % CI = 0.62 - 1.13 ; P-trend = 0.03 ) . Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence ( OR for any compared with no use = 0.82 ; 95 % CI = 0.68 - 0.99 ; and OR = 0.82 ; 95 % CI = 0.68 - 0.99 ; for calcium and vitamin D , respectively ) . Slightly stronger associations were noted for the prevention of multiple recurrences . Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake ( P = 0.14 ) on risk for adenoma recurrence . This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence", "BACKGROUND Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk , no r and omized trial has evaluated these relationships . METHODS Postmenopausal women ( N = 36 282 ) who were enrolled in a Women 's Health Initiative clinical trial were r and omly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3 ) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture . Mammograms and breast exams were serially conducted . Invasive breast cancer was a secondary outcome . Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects . A Cox proportional hazards model was used to estimate the risk of breast cancer associated with r and om assignment to calcium with vitamin D(3 ) . Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake , body mass index ( BMI ) , recreational physical activity , and breast cancer risks were evaluated using logistic regression models . Statistical tests were two-sided . RESULTS Invasive breast cancer incidence was similar in the two groups ( 528 supplement vs 546 placebo ; hazard ratio = 0.96 ; 95 % confidence interval = 0.85 to 1.09 ) . In the nested case-control study , no effect of supplement group assignment on breast cancer risk was seen . Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake ( diet and supplements ) ( r = 0.19 , P Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity ( P(trend ) = .20 ) . CONCLUSIONS Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women . In addition , 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk . These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk", "The objective of this study was to determine whether vitamin D supplementation of breast-fed infants during the first year of life is associated with greater bone mineral content and /or areal bone mineral density ( aBMD ) in later childhood . The design was a retrospective cohort study . One hundred and six healthy prepubertal Caucasian girls ( median age , 8 yr ; range , 7 - 9 yr ) were classified as vitamin D supplemented or unsupplemented during the first year of life on the basis of a question naire sent to participating families and their pediatricians . Bone area ( square centimeters ) and bone mineral content ( grams ) were determined by dual energy x-ray absorptiometry at six skeletal sites . Vitamin D receptor ( VDR ) 3'-gene polymorphisms ( BsmI ) were also determined . The supplemented ( n = 91 ) and unsupplemented ( n = 15 ) groups were similar in terms of season of birth , growth in the first year of life , age , anthropometric parameters , and calcium intake at time of dual energy x-ray absorptiometry . The supplemented group had higher aBMD at the level of radial metaphysis ( mean + /- SEM , 0.301+/-0.003 vs. 0.283+/-0.008 ; P = 0.03 ) , femoral neck ( 0.638+/-0.007 vs. 0.584+/-0.021 ; P = 0.01 ) , and femoral trochanter ( 0.508+/-0.006 vs. 0.474+/-0.016 ; P = 0.04 ) . At the lumbar spine level aBMD values were similar ( 0.626+/-0.006 vs. 0.598+/-0.019 ; P = 0.1 ) . In a multiple regression model taking into account the effects of vitamin D supplementation , height , and VDR genotype on aBMD ( dependent variable ) , femoral neck aBMD remained higher by 0.045 g/cm2 in the supplemented group ( P = 0.02 ) . Vitamin D supplementation in infancy was found to be associated with increased aBMD at specific skeletal sites later in childhood in prepubertal Caucasian girls", "Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies . Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [ 25(OH)D ] . Pancreatic islet and duct cells express 25(OH)D(3)-1alpha-hydroxylase that generates the biologically active 1,25(OH)(2 ) vitamin D form . Thus , 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology . We conducted a prospect i ve nested case-control study in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention cohort of male Finnish smokers , ages 50 to 69 years at baseline , to test whether more adequate vitamin D status , as determined by prediagnostic serum 25(OH)D concentrations , was associated with lower pancreatic cancer risk . Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 ( up to 16.7 years of follow-up ) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed . Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were calculated using conditional logistic regression . Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer ( highest versus lowest quintile , > 65.5 versus pancreatic cancer risk compared with those with lower status . Our findings need to be replicated in other population s and caution is warranted in their interpretation and implication . Our results are intriguing and may provide clues that further the underst and ing of the etiology of this highly fatal cancer", "BACKGROUND Calcium and vitamin D both appear to have antineoplastic effects in the large bowel . Although these nutrients are inter-related metabolically in bone and in the normal intestine , their potential interactions in large-bowel carcinogenesis are not well understood . METHODS We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center , placebo-controlled r and omized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence . Serum levels of 25-hydroxy [ 25-(OH ) ] vitamin D and 1,25-dihydroxy [ 1,25-(OH)2 ] vitamin D levels were determined , and the Taq I and Fok I polymorphisms in the vitamin D receptor ( VDR ) gene were analyzed by polymerase chain reaction . Risk ratios ( RRs ) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups . Associations of VDR polymorphisms with recurrence risk were also evaluated . All statistical tests were two-sided . RESULTS Among subjects with baseline 25-(OH ) vitamin D levels at or below the median ( 29.1 ng/mL ) , calcium supplementation was not associated with adenoma recurrence , whereas among those with levels above the median , calcium supplementation was associated with a reduced risk ( RR = 0.71 , 95 % confidence interval [ CI ] = 0.57 to 0.89 , P for interaction = .012 ) . Conversely , serum 25-(OH ) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements ( RR per 12 ng/mL increase of vitamin D = 0.88 , 95 % CI = 0.77 to 0.99 , P for interaction = .006 ) . VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium . CONCLUSIONS Calcium supplementation and vitamin D status appear to act largely together , not separately , to reduce the risk of colorectal adenoma recurrence . VDR genotype does not appear to be associated with risk", "in association with hypothyroidism . We did not obtain parietal cell or intrinsic factor antibodies . There was no evidence of other au to immune diseases or deficiencies in the mother ( or int2ant ) on the basis of routine clinical and laboratory tests . Breast-fed infants are at risk for nutr i t ional deficiencies if the mother is malnourished , a vegan , or if she has an abnormali ty in nut r ien t metabolism . Physicians should be aware tha t even with a well-balanced mate rna l diet , an occasional breast-fed infant can develop a serious nutritional deficiency", "BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this None finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . )", "Although calcium and vitamin-D intake were consistently shown to be inversely associated with colorectal cancer risk in several large prospect i ve studies and protective against adenoma and cancer in multiple r and omized trials , the Women 's Health Initiative ( WHI ) of calcium and low-dose vitamin-D supplementation trial found no overall effects on colorectal cancer . However , the previous report did not recognize an important biologic interaction with estrogen therapy . We investigated the treatment interaction of estrogen with calcium and vitamin-D on risk of colorectal cancer via a re analysis of primary data results from the WHI calcium and vitamin-D supplementation trial ( 1,000 mg elemental calcium , 400 IU of vitamin-D3 , or placebo ) , reanalyzing results from women concurrently r and omized to estrogen interventions and placebo . Results indicate that concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D supplementation on colorectal cancer risk . While calcium plus vitamin-D supplementation among women concurrently assigned to estrogen therapies suggested increased risk ( Hazard Ratio = 1.50 , 95 % CI : 0.96 - 2.33 ) , among women concurrently assigned to placebos arms of the estrogen trials , calcium plus vitamin-D indicated suggestive benefits ( HR = 0.71 , 95 % CI : 0.46 - 1.09 ) ( p-for-estrogen-interaction = 0.018 ) . Consistent interaction was also found by reported estrogen use ( p interaction = 0.037 ) . Results indicate contrasting effects of calcium and vitamin-D by concurrent estrogen therapy on colorectal cancer risk . Although further clinical and mechanistic studies are warranted , the potential clinical implication s of the apparent interaction of estrogen therapy with calcium and vitamin-D supplementation should be recognized . Important biological mechanisms related to the key membrane receptor megalin and estrogen-dependent protein calbindin are discussed", "To determine whether amounts of vitamin D lower than recommended doses are effective in preventing rickets , 256 term infants from two northern and two southern cities in China were studied in a r and omized trial of vitamin D supplementation ( 100 , 200 , or 400 IU/day ) during the first 6 months of life . Cord blood and 6-month blood sample s were collected and radiographs were obtained at 3 to 5 days and at 6 months of age . Cord serum 25-hydroxyvitamin D concentrations were lower in the north than in the south ( 5 vs 14 ng/ml ( 12.5 vs 35.0 nmol/L ) ; p less than 0.01 ) . Wrist ossification centers were less likely to be present at birth in the northern children than in the southern children ( p = 0.009 ) and were more likely to be present in infants born in the fall who had higher cord serum concentrations of 25-hydroxyvitamin D ( p = 0.04 ) . Serum 25-hydroxyvitamin D concentrations were lower in northern children 6 months of age than in southern children ( p = 0.005 ) and were higher with an increasing supplemental dosage of vitamin D ( p less than 0.001 ) , particularly in infants in the north . None of the infants had rickets at 6 months of age . Because of the low serum 25-hydroxyvitamin D concentrations , especially among infants in the north , it may be prudent to supplement the diet with vitamin D at a dose of 400 IU/day" ]	41183c86-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Panic disorder is characterised by repeated , unexpected panic attacks , which represent a discrete period of fear or anxiety that has a rapid onset , reaches a peak within 10 minutes , and in which at least four of 13 characteristic symptoms are experienced , including racing heart , chest pain , sweating , shaking , dizziness , flushing , stomach churning , faintness and breathlessness . It is common in the general population with a lifetime prevalence of 1 % to 4 % . The treatment of panic disorder includes psychological and pharmacological interventions . Amongst pharmacological agents , the National Institute for Health and Care Excellence ( NICE ) and the British Association for Psychopharmacology consider antidepressants , mainly selective serotonin reuptake inhibitors ( SSRIs ) , as the first-line treatment for panic disorder , due to their more favourable adverse effect profile over monoamine oxidase inhibitors ( MAOIs ) and tricyclic antidepressants ( TCAs ) . Several classes of antidepressants have been studied and compared , but it is still unclear which antidepressants have a more or less favourable profile in terms of effectiveness and acceptability in the treatment of this condition . OBJECTIVES To assess the effects of antidepressants for panic disorder in adults , specifically:1 . to determine the efficacy of antidepressants in alleviating symptoms of panic disorder , with or without agoraphobia , in comparison to placebo;2 . to review the acceptability of antidepressants in panic disorder , with or without agoraphobia , in comparison with placebo ; and 3 . to investigate the adverse effects of antidepressants in panic disorder , with or without agoraphobia , including the general prevalence of adverse effects , compared to placebo . SEARCH METHODS We search ed the Cochrane Common Mental Disorders ' ( CCMD ) Specialised Register , and CENTRAL , MEDLINE , EMBASE and PsycINFO up to May 2017 . We h and search ed reference lists of relevant papers and previous systematic review s. SELECTION CRITERIA All double-blind , r and omised , controlled trials ( RCTs ) allocating adults with panic disorder to antidepressants or placebo . DATA COLLECTION AND ANALYSIS Two review authors independently checked eligibility and extracted data using a st and ard form . We entered data into Review Manager 5 using a double-check procedure . Information extracted included study characteristics , participant characteristics , intervention details and setting s. Primary outcomes included failure to respond , measured by a range of response scales , and treatment acceptability , measured by total number of dropouts for any reason . Secondary outcomes included failure to remit , panic symptom scales , frequency of panic attacks , agoraphobia , general anxiety , depression , social functioning , quality of life and patient satisfaction , measured by various scales as defined in individual studies . We used GRADE to assess the quality of the evidence for each outcome MAIN RESULTS : Forty-one unique RCTs including 9377 participants overall , of whom we included 8252 in the 49 placebo-controlled arms of interest ( antidepressant as monotherapy and placebo alone ) in this review . The majority of studies were of moderate to low quality due to inconsistency , imprecision and unclear risk of selection and performance bias . We found low- quality evidence that revealed a benefit for antidepressants as a group in comparison with placebo in terms of efficacy measured as failure to respond ( risk ratio ( RR ) 0.72 , 95 % confidence interval ( CI ) 0.66 to 0.79 ; participants = 6500 ; studies = 30 ) . The magnitude of effect corresponds to a number needed to treat for an additional beneficial outcome ( NNTB ) of 7 ( 95 % CI 6 to 9 ) : that means seven people would need to be treated with antidepressants in order for one to benefit . We observed the same finding when classes of antidepressants were compared with placebo . Moderate- quality evidence suggested a benefit for antidepressants compared to placebo when looking at number of dropouts due to any cause ( RR 0.88 , 95 % CI 0.81 to 0.97 ; participants = 7850 ; studies = 30 ) . The magnitude of effect corresponds to a NNTB of 27 ( 95 % CI 17 to 105 ) ; treating 27 people will result in one person fewer dropping out . Considering antidepressant classes , TCAs showed a benefit over placebo , while for SSRIs and serotonin-norepinephrine reuptake inhibitor ( SNRIs ) we observed no difference . When looking at dropouts due to adverse effects , which can be considered as a measure of tolerability , we found moderate- quality evidence showing that antidepressants as a whole are less well tolerated than placebo . In particular , TCAs and SSRIs produced more dropouts due to adverse effects in comparison with placebo , while the confidence interval for SNRI , noradrenergic reuptake inhibitors ( NRI ) and other antidepressants were wide and included the possibility of no difference . AUTHORS ' CONCLUSIONS The identified studies comprehensively address the objectives of the present review .Based on these results , antidepressants may be more effective than placebo in treating panic disorder . Efficacy can be quantified as a NNTB of 7 , implying that seven people need to be treated with antidepressants in order for one to benefit . Antidepressants may also have benefit in comparison with placebo in terms of number of dropouts , but a less favourable profile in terms of dropout due to adverse effects . However , the tolerability profile varied between different classes of antidepressants . The choice of whether antidepressants should be prescribed in clinical practice can not be made on the basis of this review . Limitations in results include funding of some studies by pharmaceutical companies , and only assessing short-term outcomes . Data from the present review will be included in a network meta- analysis of psychopharmacological treatment in panic disorder , which will hopefully provide further useful information on this issue	[ "The efficacy of tricyclics and benzodiazepines in the short term ( approximately 2 - 4 months ) treatment of panic disorder is well demonstrated , but efficacy over the longer term is not considered established . The present study provided systematic data from a double blind comparison of maintenance therapy ( up to 8 months ) of panic disorder with or without agoraphobia with alprazolam , imipramine , or placebo in 181 patients who had responded to the same regimen in a r and omized 8-week treatment trial . All three groups had improved during the first 2 months ( active treatments more than placebo and about equal to each other ) , and all maintained or extended their improvement over the next 6 months without any significant change in dose . More than twice as many alprazolam and imipramine than placebo patients ( 15 % ) remained in treatment for the full 8 months and did slightly better on symptom measures than the remaining placebo patients . Both medications were well tolerated during the maintenance period . The data suggest sustained efficacy and safety of imipramine and alprazolam over an extended period . More specifically , they suggest that tolerance does not develop to the therapeutic effects of either drug", "CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data", "Seventy-nine patients with panic disorder were r and omized to an 8-week double-blind treatment with alprazolam , imipramine , or placebo . Patients kept daily records of panic attacks , activity , anxiety , sleep , and medication use . Weekly measures of anxiety , depression , somatic symptoms , fears , avoidance , disability , and improvement were obtained . All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures . By physician and patient global assessment , patients receiving alprazolam or imipramine were significantly better than patients on placebo . The alprazolam effects were apparent by week 1 ; the imipramine effects by week 4 . All groups showed significant reductions in anxiety , depression , somatic measures , and panic attack frequency . At 8 weeks , patients in the alprazolam group reported significantly less fear than patients in the other two groups . Subjects in the imipramine group showed a significant increase in heart rate and blood pressure", "BACKGROUND The serotonin selective reuptake inhibitors are increasingly being used for the treatment of panic disorder . We examined the efficacy and safety of the serotonin selective reuptake inhibitor sertraline hydrochloride in patients with panic disorder . METHODS One hundred seventy-six nondepressed out patients with panic disorder , with or without agoraphobia , from 10 sites followed identical protocol s that used a flexible-dose design . After 2 weeks of single-blind placebo , patients were r and omly assigned to 10 weeks of double-blind , flexible-dose treatment with either sertraline hydrochloride ( 50 - 200 mg/d ) or placebo . RESULTS Sertraline-treated patients exhibited significantly greater improvement ( P=.01 ) at end point than did patients treated with placebo for the primary outcome variable , panic attack frequency . Significant differences between groups were also evident for clinician and patient assessment s of improvement as measured by the Clinical Global Impression Improvement ( P=.01 ) and Severity ( P=.009 ) Scales , Panic Disorder Severity Scale ratings ( P=.03 ) , high end-state function assessment ( P=.03 ) , Patient Global Evaluation rating ( P=.01 ) , and quality of life scores ( P=.003 ) . Adverse events , generally characterized as either mild or moderate , were not significantly different in overall incidence between the sertraline and placebo groups . CONCLUSION Results support the safety and efficacy of sertraline for the short-term treatment of patients with panic disorder", "ABSTRACT A double‐blind clinical trial of zimeldine , a potent inhibitor of central serotonin reuptake , versus imipramine and placebo was carried out on 44 patients suffering from agoraphobia with panic attacks . Zimeldine was a superior treatment on all rating scales other than a global rating scale which did not reach statistically significant superiority . Imipramine was not shown to be superior to placebo . The implication s of these results for further research on the underlying pathophysiology of agoraphobia with panic attacks are discussed", "Several reports suggest that selective serotonin reuptake blockers are helpful in the treatment of panic disorder . The aim of the study was to compare fluvoxamine with placebo in 50 panic disorder patients by using an 8-week , double-blind , parallel-groups design . Weekly assessment included a panic attack diary ( frequency and severity ) , the Montgomery-Asberg Depression Scale , the Clinical Anxiety Scale , and the Sheehan Disability Scale . Although both groups improved on all measures , the fluvoxamine group experienced significantly less frequent major panic attacks from the third week on and significantly lower ratings on anxiety , depression , and disability from the sixth week on . Mean ratings of the severity of major and the severity and frequency of minor attacks were not affected differently by fluvoxamine and placebo . At the end of the study , significantly more patients on fluvoxamine were free of major and minor panic attacks . The results indicate that : ( 1 ) the administration of fluvoxamine , as compared with placebo , led to a significant reduction in the number of panic attacks . ( 2 ) The severity of panic attacks was not affected by fluvoxamine . ( 3 ) The effect of fluvoxamine on anxiety , depressive mood , and disability differed from placebo only after 6 weeks of treatment , after which the placebo group showed either no further improvement or a reversal of symptoms . ( 4 ) Participation in a drug study , even without additional psychotherapy , led to significant improvement in all patients", "BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder", "The efficacy of buspirone for panic disorder was tested in 60 patients who met Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . ) criteria for panic disorder or agoraphobia with panic attacks . Patients were r and omly assigned to treatment with buspirone ( mean dose 29.5 mg/day ) , imipramine ( mean dose 140 mg/day ) , or placebo , and treated for 8 weeks after a 4- to 7-day placebo lead-in period . Patients with 4 or fewer attacks per month and those without attacks at the baseline visit were excluded from panic frequency comparisons . Both buspirone and imipramine tended to be better than placebo on total number of panic attacks , global psychopathology , and the Hamilton Anxiety rating scale , but end point differences among treatments were not statistically significant . At the end of the study , 25 % of the buspirone patients were panic-free , as were 7 % of the imipramine patients and 14 % of the placebo patients ; again , these differences were not statistically significant . The results of this study were inconclusive , partly because of the relatively small number of patients ( 10 - 11 ) completing the study in each treatment group , and partly because of a robust placebo response in this population . Possible reasons for this high placebo response are discussed , as well as suggestions for changes in study design for future studies", "This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode , Dysthymia , or Depressive Disorder NOS . The study 's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam , imipramine and placebo on anxiety outcomes . A placebo-controlled , double-blind , parallel r and om assignment design was utilized over a total of 16 weeks . There was no medication effect on panic outcomes . At endpoint , percent of anticipatory anxiety ( i.e. , time spent worrying about having an anxiety attack ) was significantly lower in the patients taking active medications vs. placebo . Phobic measures were significantly improved by alprazolam , vs. both imipramine and placebo early in the study ; however , by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms . In addition , both active medications were significantly more effective than placebo in reducing depression . The same efficacy pattern ( i.e. , active medications superior to placebo ) was observed on measures of general functioning . Importantly , there were no significant interactions observed between medication and presence of major depression on the depression measures , indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression . Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range , these results may not be transferrable to patients with panic disorder and severe major depression", " Among 79 volunteer , unpaid , family doctor-referred psychiatric out patients with DSM III-R panic disorder , with and without agoraphobia , 66 completed a six week placebo-controlled trial of lofepramine versus clomipramine and 57 survivors were followed up for 6 months . All subjects received one hour per week concurrent behavioural counselling in the acute phase . Of 13 dropouts in the first 3 weeks , 9 ( of 27 ) were on clomipramine , 2 ( of 26 ) were on lofepramine and 2 ( of 26 ) were on placebo . The high ( 30 % ) early dropout from the clomipramine group was largely due to medication intolerance . Both drugs were superior to placebo by the end of week 6 on several st and ard rating scales but not on panic attack frequency . No significant differences in efficacy were found between the two drugs tested to the end of 6 months . No tendency for relapse was noted in the three months following taper-off of medication from week 12 to week 24 . The study provides evidence that both drugs , in the dosages used , are superior to placebo in the acute phase of panic disorder in treatment-naive subjects concurrently receiving appropriate psychotherapy", "This paper reports the results of a double-blind comparison of fixed daily doses of 6 mg of alprazolam , 2 mg of alprazolam , 225 mg of imipramine , and placebo for 8 weeks in 81 patients who met DSM-III criteria for panic disorder with or without agoraphobia . Final scores on eight clinical measures were analyzed from all patients who entered the study and from the subset who completed at least 4 weeks of treatment . Eighty-six percent of the high-dose alprazolam patients completed the study . Only 50 % of the imipramine patients completed 8 weeks of treatment , apparently because of activation early in treatment and slow onset of therapeutic effects . This study confirmed the therapeutic effectiveness and safety of alprazolam , especially at the higher dose , in panic disorder . It also confirmed the therapeutic effectiveness of imipramine among patients who tolerated the drug . It suggested the usefulness of a flexible , individual approach to dose escalation with imipramine . Method ologically the study underscored the importance of using multiple approaches to the analysis of clinical data from therapeutic trials of psychotropic agents with complex effects that may contribute to patients ' premature termination", "OBJECTIVE This study determined the efficacy and safety of sertraline in the treatment of patients with panic disorder . METHOD The study was a r and omized , double-blind , parallel-group , flexible-dose comparison of sertraline and placebo in out patients with a DSM-III-R diagnosis of panic disorder with or without agoraphobia . After a 2-week single-blind placebo lead-in , 168 patients entered a 10-week double-blind phase in which they were r and omly assigned to treatment with either sertraline or placebo . RESULTS Sertraline was significantly more effective than placebo in decreasing the number of full and limited-symptom panic attacks . Among patients who completed the study , the mean number of panic attacks per week dropped by 88 % in the sertraline-treated patients and 53 % in the placebo-treated patients . Sertraline-treated patients also had significantly more improvement than placebo-treated patients in scores on the Quality of Life Enjoyment and Satisfaction Question naire , patient global evaluation , and Clinical Global Impression severity of illness and global improvement scales . Overall , patients tolerated sertraline well , and only 9 % terminated treatment because of side effects . CONCLUSIONS Sertraline is an effective and well-tolerated treatment for patients with panic disorder", " Summary The relevance of the chronology between panic disorder and avoidance behavior and of an early , medium or late onset of panic disorder was tested . Groups from the sample of the cross-national collaborative panic study ( CNCPS ) were compared for differences in basic characteristics and for the ability to predict treatment response . Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment . Patients with an early onset of panic disorder suffered more often from agoraphobia . The treatment response was similar in the groups with early , medium or late onset of panic disorder . Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or impiramine", "OBJECTIVE Recently , pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available . The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines . METHOD A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project , a prospect i ve longitudinal study of anxiety disorders . These patients were interviewed over the course of 10 years to examine their use of psychotropic medications . RESULTS Despite efforts aim ed at increasing the use of selective serotonin reuptake inhibitors ( SSRIs ) in patients with panic disorder ( e.g. , APA 's practice guideline for panic disorder , Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder ) , only a modest increase in their use was found . Treatment patterns for psychotropic drugs appear to have remained stable over the past decade , with benzodiazepines being the most commonly used medication for panic disorder . In comparison , SSRI use throughout the follow-up period has remained low . Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine , nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly . CONCLUSIONS These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed . Factors potentially associated with promoting and ignoring treatment recommendations are discussed", "In a controlled- outcome study of phobias , 218 adult phobic patients ( 147 women and 71 men ) received a course of 26 weekly treatment sessions that consisted of behavior therapy ( BT ) and imipramine hydrochloride , BT and placebo , or supportive psychotherapy and imipramine . The BT consisted of systematic desentization using fantasy and assertiveness training . Patients were classified as agoraphobic , mixed phobic , or simple phobic . Although the conditions of most patients in each group showed moderate to marked improvement , the effects of imipramine were significantly superior to those of placebo in patients with spontaneous panic attacks , ie , patients with agoraphobia or mixed phobia . In patients with simple phobia , who do not experience spontaneous panic , there was not a significant difference between imipramine and placebo . This study clearly distinguished those phobic patients who experienced spontaneous panic from those who did not in terms of pharmacologic benefits", "Patients with panic disorder ( N = 1168 ) were enrolled in a multicenter , 8-week , double-blind clinical trial of imipramine , alprazolam , and placebo to analyze whether the effectiveness of these agents is dependent on the depressive/dysphoric symptomatology which often coexists in panic disorder patients . In addition to analyses performed on the whole sample of patients , the authors conducted analyses on a sub sample ( N = 312 ) defined by multiple criteria to ensure the absence of depression and dysphoria . In both the overall sample and the nondepressed sub sample , the clinical response to imipramine or alprazolam was found to be independent of the presence of depression or dysphoria . In panic disorder patients for whom pharmacotherapy is being considered as treatment , the absence of depression is apparently not a contraindication", "BACKGROUND The Panic Disorder Severity Scale ( PDSS ) is promising to be a st and ard global rating scale for panic disorder . In order for a clinical scale to be useful , we need a guideline for interpreting its scores and their changes , and for defining clinical change points such as response and remission . METHODS We used individual patient data from two large r and omized controlled trials of panic disorder ( total n=568 ) . Study participants were administered the PDSS and the Clinical Global Impression (CGI)--Severity and --Improvement . We applied equipercentile linking technique to draw correspondences between PDSS and CGI-Severity , numeric changes in PDSS and CGI-Improvement , and percent changes in PDSS and CGI-Improvement . RESULTS The interpretation of the PDSS total score differed according to the presence or absence of agoraphobia . When the patients were not agoraphobic , score ranges 0 - 1 corresponded with \" Normal , \" 2 - 5 with \" Borderline , \" 6 - 9 with \" Slightly ill , \" 10 - 13 with \" Moderately ill , \" and 14 and above with \" Markedly ill . \" When the patients were agoraphobic , score ranges 3 - 7 meant \" Borderline ill , \" 8 - 10 \" Slightly ill , \" 11 - 15 \" Moderately ill , \" and 16 and above \" Markedly ill . \" The relationship between PDSS change and CGI-Improvement was more linear when measured as percentile change than as numeric changes , and was indistinguishable for those with or without agoraphobia . The decrease by 75 - 100 % was considered \" Very much improved , \" that by 40 - 74 % \" Much improved , \" and that by 10 - 39 % \" Minimally improved . \" CONCLUSION We propose that \" remission \" of panic disorder be defined by PDSS scores of five or less and its \" response \" by 40 % or greater reduction", "Seventy-five out patients with moderate to severe panic disorder were r and omly assigned to receive 8 weeks of fluvoxamine , cognitive therapy , or placebo . Fifty-five patients completed the treatment protocol . Fluvoxamine was found to be an effective and well-tolerated treatment for panic using clinician- and patient-rated variables . Subjects receiving cognitive therapy also showed improvement , but this improvement did not significantly differ from the experience of the placebo-treated group for most comparisons . Fluvoxamine was superior to cognitive therapy for many ratings , but cognitive therapy was not superior to fluvoxamine on any rating . Fluvoxamine also produced improvement earlier than cognitive therapy . At the main comparison point ( week 4 ) , 57 % ( 13/23 ) of patients receiving fluvoxamine were rated moderately improved or better vs 40 % ( 8/20 ) of the group given cognitive therapy and 22 % ( 5/23 ) of the placebo-treated group . At that point , 43 % ( 10/23 ) of the fluvoxamine recipients vs 25 % ( 5/20 ) of cognitive therapy and 4 % ( 1/23 ) of placebo recipients were free of panic attacks", "Clinical trials of drug treatments for psychiatric disorders commonly employ the parallel groups , placebo-controlled , repeated measure r and omized comparison . When patients stop adhering to their originally assigned treatment , investigators often ab and on data collection . Thus , non-adherence produces a monotone pattern of unit-level missing data , disabling the analysis by intent-to-treat . We propose an approach based on multiple imputation of the missing responses , using the approximate Bayesian bootstrap to draw ignorable repeated imputations from the posterior predictive distribution of the missing data , stratifying by a balancing score for the observed responses prior to withdrawal . We apply the method and some variations to data from a large r and omized trial of treatments for panic disorder , and compare the results to those obtained by the original analysis that used the st and ard ( endpoint ) method", "One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder , panic disorder with limited phobic avoidance , or uncomplicated panic disorder entered an acute 8-week treatment phase . Patients who improved received an additional 6 months ' maintenance treatment . Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase . During the maintenance phase , neither tolerance nor daily dose increase was observed . All patients who completed the maintenance phase ( 27 in the alprazolam group , 11 in the imipramine group , and 10 in the placebo group ) were panic free at the end of 8 months of study treatment . Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg . Imipramine hydrochloride ( 175 mg/d ) also produced significant panic relief but was associated with poor patient acceptance", "BACKGROUND Panic disorder , with and without agoraphobia , is a prevalent condition which presents primarily in general practice . Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital setting s , and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care . AIM To evaluate the outcome , in a primary care setting , of fluvoxamine versus cognitive behaviour therapy , each used alone and in combination in a double-blind placebo-controlled framework , balanced for therapist contact . METHOD A total of 149 patients satisfying DSMIII-R criteria for panic disorder were r and omly allocated to receive one of the following : fluvoxamine , placebo , fluvoxamine plus cognitive behaviour therapy , placebo plus cognitive behaviour therapy , and cognitive behaviour therapy alone . These five treatment groups represent the minimum number acceptable for such a comparison to be made . All patients received an identical schedule of contact over 13 weeks . Measures of symptom severity , general health and social disruption were taken at entry point and end point ; measures of change in symptoms were taken at end point only . Outcome was reported in terms of brief global ratings of severity of illness and change in symptoms , and of ratings of general health and social disruption that are suitable for use in general practice . RESULTS All active treatment groups showed statistically significant advantages over placebo over a range of outcome ratings . The groups employing cognitive behaviour therapy showed the most robust and consistent response . CONCLUSION The brief global measures reported here proved adequate to the task of assessing treatment outcome . Results indicate that treatments including cognitive behaviour therapy can be effective in the treatment of panic disorder and agoraphobia in primary care", "This study compared the efficacy , tolerability , and safety of fluvoxamine , imipramine , and placebo in the treatment of panic disorder with or without agoraphobia . Fifty-four out patients participated in the r and omized , double-blind trial as part of a multicenter trial . After meeting inclusion criteria and completing screening requirements ( e.g. , laboratory testing , electrocardiogram , physical examination ) , patients were entered in a single-blind placebo washout phase . They were then r and omized to either fluvoxamine , imipramine , or placebo . Measurements completed at each visit included the number and severity of panic attacks per week , the Sheehan Panic and Anticipatory Anxiety Scale , and the Clinical Global Impressions , and others . Results show that fluvoxamine is more effective than placebo and as effective as imipramine in reducing spontaneous panic attacks in moderate to severe panic disorder . However , starting doses of fluvoxamine and imipramine should be low to minimize untoward side effects ( such as insomnia and agitation ) and maintain compliance", "Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment . The safety , side effects and patients ' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study . Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation , fatigue/weakness , memory problems , ataxia and slurred speech . In the imipramine group blurred vision , tachycardia/palpitations , insomnia , sleep disturbance , excitement/nervousness , malaise , dizziness/faintness , headache , nausea/vomiting and decrease in appetite were worse than in the other groups . In the placebo group the anxious symptoms were most prominent . The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group . Strong predictors of side effects were not observed . If a side effect profile is known , it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance , safety and efficacy in each patient under treatment . Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients ' quality of life", "Psychopharmacological studies usually attempt to eliminate \" nonspecific \" influences on outcome by double-blind design s. In a r and omized , double-blind comparison of alprazolam , imipramine , and placebo , the great majority of panic disorder patients ( N = 59 ) and their physicians were able to rate accurately whether active drug or placebo had been given . Moreover , physicians could distinguish between the two types of active drugs . Inasmuch as correct rating was possible halfway through treatment , concerns about the internal validity of the double-blind strategy arise", "BACKGROUND Although serotonin reuptake inhibitors are effective in panic disorder , questions concerning whether doses associated with antidepressant efficacy are also effective for panic disorder remain . AIMS To assess the efficacy of the usual antidepressant dose of fluoxetine in treating full panic attacks . METHOD Patients with panic disorder were r and omised to placebo or to fluoxetine initiated at 10 mg daily for 1 week and then increased to 20 mg daily . The trial lasted 12 weeks , but after 6 weeks patients who had failed to achieve a satisfactory response were eligible for dose escalation to a maximum of 60 mg of fluoxetine daily . RESULTS Fluoxetine was associated with a statistically significantly greater proportion of panic-free patients compared with placebo after 6 weeks and at end-point . CONCLUSIONS Fluoxetine at a dose of 20 mg daily is safe and efficacious in reducing symptoms of panic disorder . Patients who fail to obtain a satisfactory response at 20 mg daily may benefit from further dose increases", "As part of the cross‐national collaborative panic study , a double‐blind comparison of alprazolam , imipramine and placebo was performed in Sc and inavian out patients with panic disorder according to DSM‐III ; 41 patients were r and omly allocated to each drug . Doses were increased for 3 weeks to an average of about 6 mg alprazolam , 150 mg imipramine and a corresponding number of placebo capsules , which were then given for 5 weeks . No more than supportive psychotherapy was given . Key symptoms were rated weekly . The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months . Compliance at 3 weeks was 95 % for alprazolam , 83 % for imipramine and 88 % for placebo ; at 8 weeks 95 % for alprazolam , 73 % for imipramine and 46 % for placebo . At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0 % for alprazolam , 19 % for imipramine and 31 % for placebo ; at 8 weeks the corresponding proportions were 3 % , 11 % and 16 % . Intention‐to‐treat analysis showed that freedom from panic attacks was obtained for 68 % with alprazolam , 61 % with imipramine and 34 % with placebo . Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms . Globally rated by physicians and patients , about 60 % had complete remission with alprazolam and imipramine and 30 % on placebo . At least partial remission was obtained in about 85 % with alprazolam , 70 % with imipramine and 40 % with placebo . Alprazolam had a more rapid onset of action than imipramine on all symptoms . Side effects were generally mild , with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine . Tapering was uneventful without significant discontinuation phenomena . During taper and follow‐up , several patients in remission relapsed , leaving approximately 30 % patients in complete remission in all groups . To obtain more stable improvement , either long‐term drug treatment or combinations of drug treatment and psychotherapy should be evaluated", "Abstract This article reports the initial results of a prospect i ve study on the prevalence of psychiatric disorders in the Dutch population aged 18–64 . The objectives and the design of the study are described elsewhere in this issue . A total of 7076 people were interviewed in person in 1996 . The presence of the following disorders was determined by means of the CIDI : mood disorders , anxiety disorders , eating disorders , schizophrenia and other non-affective psychoses , and substance use disorders . Psychiatric disorders were found to be quite common . Some 41.2 % of the adult population under 65 had experienced at least one DSM-III-R disorder in their lifetime , among them 23.3 % within the preceding year . No gender differences were found in overall morbidity . Depression , anxiety , and alcohol abuse and dependence were most prevalent , and there was a high degree of comorbidity between them . The prevalence rate encountered for schizophrenia was lower ( 0.4 % lifetime ) than generally presumed . A comparison with findings from other countries is made . Relevant determinants of psychiatric morbidity were analysed", "In order to evaluate serotonin ( 5-HT ) function in panic disorder , a double blind placebo controlled study was conducted with ritanserin , a specific 5-HT2 receptor antagonist , and fluvoxamine , a selective 5-HT reuptake inhibitor , in 60 patients with panic disorder . Patients were treated for 8 weeks with 150 mg fluvoxamine , 20 mg ritanserin or placebo ; these dose levels were reached after 1 week . In addition , as an index of 5-HT function in panic disorder , plasma concentration of β-endorphin , cortisol and 5-hydroxyindolacetic-acid ( 5-HIAA ) were measured . Furthermore , 5-HT uptake in blood platelets was assessed . Noradrenergic function was assessed by measuring plasma MHPG concentration . In addition , plasma melatonin concentration was measured . Treatment with fluvoxamine result ed in a profound reduction in the number of panic attacks , followed by a decrease in avoidance behavior . Treatment with ritanserin appeared to be ineffective . During treatment no significant changes were observed in plasma concentrations of β-endorphin , cortisol , 5-HIAA and MHPG . With respect to 5-HT kinetics in blood platelets , a substantial increase in Km was observed after treatment with fluvoxamine , whereas Vmax decreased . After treatment with fluvoxamine , plasma concentration of melatonin was significantly increased , which suggests that melatonin synthesis is in part under serotonergic control . The findings of the present study do not support the hypothesis that 5-HT2 receptors are supersensitive in patients suffering from panic disorder , but allow no conclusions about the involvement of other 5-HT receptor subtypes", "BACKGROUND AND OBJECTIVE To conduct a pilot study to compare the frequency of errors that accompany single vs. double data extraction , compare the estimate of treatment effect derived from these methods , and compare the time requirements for these methods . METHODS Review ers were r and omized to the role of data extractor or data verifier , and were blind to the study hypothesis . The frequency of errors associated with each method of data extraction was compared using the McNemar test . The data set for each method was used to calculate an efficacy estimate by each method , using st and ard meta-analytic techniques . The time requirement for each method was compared using a paired t-test . RESULTS Single data extraction result ed in more errors than double data extraction ( relative difference : 21.7 % , P = .019 ) . There was no substantial difference between methods in effect estimates for most outcomes . The average time spent for single data extraction was less than the average time for double data extraction ( relative difference : 36.1 % , P = .003 ) . CONCLUSION In the case that single data extraction is used in systematic review s , review ers and readers need to be mindful of the possibility for more errors and the potential impact these errors may have on effect estimates", "The objective of this double-blind , placebo-controlled r and omized withdrawal study was to evaluate the efficacy and safety of sertraline for 8 weeks in treating Japanese patients with DSM-IV panic disorder . Patients ( n=394 ) were initially treated with 8 weeks of open-label sertraline followed by 8 weeks of double-blind treatment with either sertraline ( 50–100 mg/day ) or placebo . Responders during the open-label phase were eligible to be entered into the double-blind phase . Two hundred and forty patients were entered to the double-blind phase and r and omly assigned to receive sertraline ( n=119 ) or placebo ( n=121 ) . On the primary efficacy measure ( relapse ) , there was no significant difference between the two treatment groups ( sertraline 10.1 % ; placebo 13.2 % ) . However , the frequency of panic attacks was significantly ( P=0.012 ) lower for sertraline compared to placebo . The proportion of sertraline-treated patients who met response criteria ( Clinical Global Impression – Improvement Scale score of 1 or 2 ) at the end of double-blind phase treatment was also significantly ( P=0.003 ) higher for sertraline ( 89.9 % ) compared to placebo ( 74.4 % ) . Panic Disorder Severity Scale total score was significantly ( P=0.012 ) lower in the sertraline group compared to the placebo group . Adverse events during acute treatment were consistent with the known adverse event profile of sertraline , and the incidence of adverse events during the double-blind phase treatment was not different between sertraline and placebo", "OBJECTIVE To assess the efficacy and tolerability of controlled-release paroxetine ( paroxetine CR ) in the treatment of adults with panic disorder . METHOD Paroxetine CR ( 25 - 75 mg/day ; N = 444 ) was compared with placebo ( N = 445 ) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical , double-blind , placebo-controlled , 10-week clinical trials that were pooled for analysis . RESULTS Paroxetine CR was statistically superior to placebo in the primary outcome measure , percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint . Of the total population that completed or prematurely terminated treatment , 63 % and 53 % of paroxetine CR- and placebo-treated patients , respectively , were panic-free during the final 2 weeks ( p paroxetine CR- and placebo-treated patients , respectively , were panic-free at week 10 ( p Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale . Adverse events leading to study withdrawal were minimal and occurred in 11 % of the paroxetine CR group and 6 % of the placebo group . Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study . There were no unexpected adverse events , and serious adverse events were uncommon ( 10 [ 2.3 % ] of the 444 patients treated with paroxetine CR vs. 8 [ 1.8 % ] of the 445 patients treated with placebo ) . CONCLUSION Paroxetine CR is an effective and well-tolerated treatment for panic disorder . Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events", "Summary The Marks-Sheehan anxiety scales are the only scales where self-ratings and observer ratings are perfectly matched by the number , the content and the scaling of the items . Therefore these scales are an excellent tool to investigate the compatibility and to study different structures in self- and observer ratings . This was done by using the data material on the Marks-Sheehan scales of the Cross National Collaborative Panic Study . In this study 1168 out patients who met the DSM-III criteria for panic disorder were r and omly allocated either to alprazolam , imipramine or placebo treatment . Our results show that the Marks-Sheehan scales are highly comparable to other established rating scales . Both scales have a similar stable and consistent factor pattern for somatic symptoms but not for psychic symptoms of anxiety . Our results provide empirical evidence that the low consistencies between self- and observer ratings reported so far can be improved by using a rating scale which matches up item by item for self- and observer ratings . However , other sources of disagreement can only be solved by more elaborated item descriptions and training of patients as well as raters to obtain a better compatibility between self- and observer rating scales", "OBJECTIVE To examine the effects of long-term treatment with citalopram or clomipramine on subjective phobic symptoms in patients with panic disorder . DESIGN Double-blind , parallel-group , five-arm study . PATIENTS Patients aged 18 to 65 years with panic disorder ( DMS-III-R diagnosis ) and with no major depressive symptoms . INTERVENTIONS Four hundred and seventy-five patients were r and omized to 8 weeks of treatment with either citalopram ( 10 to 15 mg per day ; 20 to 30 mg per day ; or 40 to 60 mg per day ) , clomipramine ( 60 to 90 mg per day ) or placebo . Two hundred and seventy-nine patients continued treatment after the 8-week acute phase . OUTCOME MEASURES Phobic symptoms were assessed using the Phobia Scale and the Symptom Checklist 's ( SCL-90 ) phobia-related factors . RESULTS At all dosages , citalopram was more efficacious than placebo , with 20 to 30 mg generally being the most effective dosage . Citalopram ( 20 to 30 mg ) generally decreased phobic symptoms significantly more than placebo after Month 3 . Interpersonal sensitivity decreased when measured on the respective SCL-90 sub-scale . Alleviation of phobic symptoms generally continued to increase towards the end of the treatment . The effect of clomipramine was not as consistent . CONCLUSIONS All active treatment groups , especially the group receiving 20 to 30 mg per day of citalopram , effectively controlled phobic symptoms in patients with panic disorder . Long-term treatment with citalopram further decreased phobic symptoms", "Patients who meet DSM-III-R criteria for a diagnosis of panic disorder often show a complex mixture of psychopathological symptoms , including panic attacks ( spontaneous and situational ) , anxiety ( anticipatory and generalized ) , phobias ( fear and avoidance ) , depression/dysphoria , and social and occupational disability . Various theories about the pathogenesis of these symptoms have been advanced that focus on a given symptom ( e.g. , panic , phobia ) being primary in these disorders , with concurrent symptoms seen as epiphenomena or as secondary and reactive to a core symptom . This study , conducted on a large sample of panic disorder patients ( N = 1,168 ) , examines the temporal sequential pattern of symptom improvement in these patients , and explores how these relationships relate to various pathogenic theories . Our multiple analyses , when considered together , tend not to support any pathogenic theory that views a given symptom as being central to the overall disorder ; our findings have obvious implication s for theoreticians and clinicians interested in the study and treatment of panic and anxiety disorders", "OBJECTIVE The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo . METHOD Forty-six out patients suffering from moderate to severe panic disorder with or without agoraphobia ( DSM-III-R criteria ) were r and omly assigned to a 10-week treatment protocol of regular aerobic exercise ( running ) , clomipramine ( 112.5 mg/day ) , or placebo pills . RESULTS The dropout rate was 31 % for the exercise group , 27 % for the placebo group , and 0 % for the clomipramine group . In comparison with placebo , both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures ( analysis of variance , last-observation-carried-forward method and completer analysis ) . A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively . Depressive symptoms were also significantly improved by exercise and clomipramine treatment . CONCLUSIONS These results suggest that regular aerobic exercise alone , in comparison with placebo , is associated with significant clinical improvement in patients suffering from panic disorder , but that it is less effective than treatment with clomipramine", "Fluvoxamine and imipramine were compared to placebo in an 8-week doubleblind r and omized multicentre trial comprising of 148 out patients between 19 and 57 years of age ( mean : 35 ) with a DSM-III-R diagnosis of Panic Disorder . mean daily dose at endpoint was : fluvoxamine , 171.4 mg ; imipramine 164.7 mg . The mean number of panic attacks per week at baseline were 10.9 , 14.4 and 6.5 for fluvoxamine , imipramine and placebo , respectively . The intent-to-treat analysis of the change from baseline ( difference score ) of the number of panic attacks at endpoint revealed : a difference of 3.3 attacks ( 95 % CI : -0.3 , 6.8 ) between fluvoxamine and placebo and a difference of 6.0 attacks ( 95 % CI : 1.5 , 10.5 ) between imipramine and placebo . Treatment was stopped prematurely in 31 ( 62 % ) on fluvoxamine , 16 ( 33 % ) on imipramine and 29 ( 58 % ) on placebo . The number of patients withdrawing due to intolerance was 13 ( 26 % ) for fluvoxamine , 10 ( 21 % ) for imipramine and 4 ( 8 % ) for placebo . The number of patients withdrawing due to lack of efficacy was 10 ( 20 % ) for fluvoxamine , 4 ( 8 % ) for imipramine and 12 ( 24 % ) for placebo . Overall , this study demonstrated that fluvoxamine was not effective in the treatment of panic disorder but did show a strong effect for imipramine . A chance occurrence of significantly fewer number of panic attacks in the placebo group at baseline may limit the conclusions of this study", "At the end of a two-week single-blind placebo baseline , 43 patients with a diagnosis of panic disorder with agoraphobia without significant dysphoria-depression and with moderate to severe panic and phobic symptoms were assigned to , and 32 of them completed , a placebo-controlled ( n = 7 ) dose-response study with three weight-adjusted imipramine hydrochloride dosages : 0.5 mg/kg/d ( n = 10 ) , 1.5 mg/kg/d ( n = 9 ) , and 3 mg/kg/d ( n = 6 ) . Eleven patients , three from the medium-dose and eight from the high-dose conditions , dropped out owing to side effects . No instructions or encouragement for self-directed exposure to phobic situations or other coping strategies with panic or fear were given throughout the trial . Compliance , as assessed by pill counts and by plasma tricyclic levels , was high . Results provided strong evidence for a positive dose-response relationship on panic and phobic symptoms and confirmed earlier suggestions ( 1 ) that imipramine without concurrent exposure possesses a significant antipanic and antiphobic effect , ( 2 ) that improvement correlates primarily with imipramine but not N-desmethylimipramine plasma levels , and ( 3 ) that side effects prevent optimum dose buildup in a substantial proportion of patients with this disorder", "Summary Self-rating scales are considered to be less useful for comparing different treatments in anxiety patients than observer-rating scales . However , the empirical evidence for this assumption is not adequate . A selfrating inventory of 35 items related to anxiety was perfectly parallel with an observer-rating inventory . Both instruments were used in the Cross National Collaborative Panic Study to compare the efficacy of imipramine , alprazolam and placebo in an 8-week drug trial in a sample of 1168 out patients . The variance of the self-rating assessment s was about two times higher . Both scales were equally sensitive to change ; however , the measurement of change by means of the self-rating scale was slightly less consistent . The discriminative power of the observer-rating scale between placebo and active treatment was two to three times higher than that of the selfrating scale ; consequently the observer-rating procedure provides a more valid instrument when the efficacies of different anxiolytic treatments are compared between different groups of patients", "BACKGROUND It has been argued that measurement of outcome in panic disorder should not be limited to monitoring the number of panic attacks , but should include all domains that affect patient quality of life . METHODS Data from a r and omized prospect i ve comparison of escitalopram , citalopram , and placebo in patients with DSM-IV panic disorder were analyzed with regard to measurements of impairment of quality of life . The subscales of the Panic and Agoraphobia Scale ( P&A ) ( Panic Attacks , Agoraphobic Avoidance , Anticipatory Anxiety , Functional and Social Disability , and Worries about Health ) and the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) were analyzed . RESULTS Treatment with escitalopram was associated with significant improvement on all 5 subscales of the P&A. Citalopram was significantly different from placebo in 3 subscales . Escitalopram and citalopram were significantly better than placebo in improving quality of life ( measured by the total score of the Q-LES-Q Scale ) . Escitalopram was superior to placebo on 12 of 16 items of the Q-LES-Q , while citalopram was superior on 7 items . CONCLUSION The P&A scale was more robust than measurement of panic frequency in differentiating medication from placebo . Escitalopram treatment was associated with improvement on all assessed domains that impair quality of life in panic disorder . Measurement of clinical improvement should not be solely based on panic attack frequency , but should also include assessment of a broad range of domains that affect patient quality of life", "BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a \" positive \" study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions", "OBJECTIVE Recent studies have suggested that most patients treated for panic disorder receive forms of psychotherapy other than cognitive behavior therapy , even though there is little information about the efficacy of such treatments or how they compare to proven active treatments . The authors compared one of these other forms , emotion-focused psychotherapy ( given to 30 patients with panic disorder ) , to results obtained with recommended st and ard treatment ( either cognitive behavior therapy [ N=36 ] or imipramine [ N=22 ] ) . The authors also compared emotion-focused psychotherapy to results obtained in subjects given pill placebo ( N=24 ) . METHOD Subjects met DSM-IV criteria for panic disorder with no more than mild agoraphobia . Treatment consisted of approximately 3 months of weekly visits followed by 6 monthly maintenance visits . Assessment s were conducted after each treatment phase and at a follow-up visit after 6 months of no treatment . RESULTS Emotion-focused psychotherapy was less effective for symptoms of panic disorder than treatment with either cognitive behavior therapy or imipramine ; results obtained with emotion-focused psychotherapy after the acute and maintenance phases were similar to those seen with placebo . Treatment expectations were not different among the different groups . Patients receiving emotion-focused psychotherapy had the highest completion rate . CONCLUSIONS The results suggest that emotion-focused psychotherapy ( a supportive form of psychotherapy ) has low efficacy for the treatment of panic disorder . However , emotion-focused psychotherapy may be superior to medical management in helping patients stay in treatment", "It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments ( interaction between treatment and baseline score ) . Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks , but not for the frequency of situational panic attacks or measures of agoraphobia . This report presents similar analyses of data from a study using moclobemide . Patients ( N = 452 ) with panic disorder were r and omized to placebo or a fixed dose of moclobemide ( 75 , 150 , 300 , 600 , or 900 mg/day ) . They were treated double-blindly and evaluated at baseline and 1 , 2 , 3 , 4 , 6 , and 8 weeks later . The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary , and fear and avoidance ratings based on the patient ’s main phobia using baseline ( pre ) and end-point ( post ) values for all r and omized patients . Adjoining dose groups were combined . Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes . Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms . This study replicates the authors ’ earlier findings , except for situational panic attacks , which probably were not reliably identified . Antidepressants selectively suppress panic attacks , especially unexpected attacks , but not agoraphobia . The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinical ly separable biologic and cognitive components that respond differentially to treatment . Antidepressants benefit primarily patients with many unexpected panic attacks . Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means ( analysis of covariance )", "A double-blind placebo-controlled study of 5-HTP and clomipramine was carried out on 45 patients suffering from anxiety disorders ( DSM-III ) . Clomipramine has shown to be effective in that it induced significant improvement on all rating scales as compared to placebo . 5-HTP showed a moderate reduction of the symptomatology on the 90-item symptoms checklist ( SCL-90 ) and the State Scale of the Spielberger State-Trait Anxiety Inventory . Clomipramine and 5-HTP differed in their efficacy in that 5-HTP did not affect the associated depressive symptomatology . The results support the hypothesis that brain serotonergic pathways are involved in the pathogenesis of anxiety disorders , particularly in agoraphobia and panic disorders", "BACKGROUND This study investigates the naturalistic course of panic disorder over four years and attempts to identify predictors for outcome . METHOD 423 DSM-III-R panic disorder patients who had taken part in an international multicentre drug trial were selected for follow-up ; we were able to re-interview 367 ( 87 % ) . For panic attacks , phobic avoidance and disabilities the same rating scales were administered as had been used for the clinical trials . RESULTS While 61 % of all patients experienced at least occasional panic attacks at follow-up , few suffered from serious phobic avoidance ( 16.7 % ) or serious disabilities ( work 7.9 % ) ; family 8.7 % ; social 13.9 % ) . Panic attack frequency at baseline , original trial medication and continuous use of psychotropic medication during follow-up are not related to outcome , whereas longer duration of illness and more severe phobic avoidance at baseline are unfavourable . CONCLUSION The course of panic disorder is not uniform . Since long duration of illness and severe phobic avoidance at baseline are predictors for an unfavourable outcome , more rigorous efforts should be undertaken to detect and treat panic disorder at an early stage", "BACKGROUND A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia , the Panic and Agoraphobia Scale ( P & A ) . The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients ( panic attacks , avoidance , anticipatory anxiety , disability and worries about health ) . The application of this scale in a double-blind placebo-controlled panic disorder trial is described . At the same time , the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy . METHODS Patients with Panic disorder ( DSM-IV ) were r and omly assigned to three treatment modalities : running ( n=45 ) , clomipramine ( n=15 ) or placebo ( n=15 ) . Treatment efficacy was measured with the Panic and Agoraphobia Scale ( P & A ) and other rating scales . RESULTS According to the P & A and other scales , both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment . Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise . The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability . CONCLUSIONS The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments . Analysis of the scales five subscores may help to underst and mechanisms of action of panic disorder treatments", "Antidepressants reportedly increase appetite , carbohydrate craving and weight in some patients with depression and panic disorder . This paper presents the results of changes in appetite and weight in patients with panic disorder treated with imipramine , diazepam or placebo in a double-blind prospect i ve study . Forty-four patients with panic disorder were r and omly assigned imipramine , diazepam and placebo . The investigators monitored weight and the patients rated their appetite and cravings during the eight week study . No significant increases in weight or appetite were found in the patients with panic disorder patients", "To date , no large-scale , controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported . This double-blind study compares the efficacy of venlafaxine extended-release ( ER ) and paroxetine with placebo . A total of 664 nondepressed adult out patients who met DSM-IV criteria for panic disorder ( with or without agoraphobia ) were r and omly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER ( 75 mg/day or 150 mg/day ) , or paroxetine 40 mg/day . The primary measure was the percentage of patients free from full-symptom panic attacks , assessed with the Panic and Anticipatory Anxiety Scale ( PAAS ) . Secondary measures included the Panic Disorder Severity Scale , Clinical Global Impressions -- Severity ( CGI-S ) and --Improvement ( CGI-I ) scales ; response ( CGI-I rating of very much improved or much improved ) , remission ( CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks ) ; and measures of depression , anxiety , phobic fear and avoidance , anticipatory anxiety , functioning , and quality of life . Intent-to-treat , last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo . No significant differences were observed between active treatment groups . Panic-free rates at end point with active treatment ranged from 54 % to 61 % , compared with 35 % for placebo . Approximately 75 % of patients given active treatment were responders , and nearly 45 % achieved remission . The placebo response rate was slightly above 55 % , with remission near 25 % . Adverse events were mild or moderate and similar between active treatment groups . Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder", "Forty-eight patients with panic disorder completing 8 months of maintenance treatment with alprazolam ( mean dose , 5.2 mg [ n = 27 ] ) , imipramine hydrochloride ( mean dose , 175 mg [ n = 11 ] ) , or placebo ( mean dose , 8.0 pills [ n = 10 ] ) underwent a gradual taper from medication over a 4-week period . A withdrawal syndrome was observed in almost all alprazolam-treated patients but in only a few imipramine- or placebo-treated patients . The clinical worsening of withdrawal symptoms after discontinuation tended to subside over the course of 3 medication-free weeks , but 33 % of alprazolam-treated patients were unable to discontinue their medication regimen successfully . Severity of panic attacks at baseline but not daily alprazolam dose appeared as a significant independent predictor of taper difficulty . Forty-nine percent of the total study population continue to receive drug therapy : 82 % alprazolam and 18 % imipramine . Among patients who received alprazolam during study treatment and at follow-up , the mean daily dose was substantially reduced ( 6.1 vs 1.6 mg [ n = 14 ] ) . At follow-up , after 1 year of naturalistic treatment for panic symptoms and combining 8-month completers and study dropouts , there were no significant differences in remission ( 68 % to 71 % ) or in antipanic medication intake ( 39 % to 56 % ) at follow-up for the three original treatment groups . However , 8-month study completers compared with study dropouts had a significantly higher remission rate ( 85 % vs 55 % )", "Factors that predicted the outcome of drug treatment ( alprazolam or imipramine ) of panic disorder were studied in a sample of 123 Sc and inavian patients participating in a multicenter placebo‐controlled 8‐week trial . The attrition rate was 95 % for alprazolam , 73 % for imipramine and 46 % for placebo . For the intention‐to‐treat and 3‐week‐completer sample s , drugs and anxiety symptoms at baseline were the best predictors of improvement on the Global Improvement Scale and on symptom scales focusing on panic attacks , phobic behavior and anticipatory anxiety . For completers of the 8‐week trial , only baseline scores predicted outcome . Generally , more severe symptoms at baseline predicted a worse outcome . A sub sample of patients had a marked placebo response . Avoidance , sex , age , childhood psychopathology and previous treatment experience had no or only a weak impact on the outcome . The relationship between panic disorder and mood disorder is presented elsewhere", "Objective : Several studies have documented that a variety of pharmacological compounds are quite effective in controlling acute symptomatology of panic disorder in the general population . However , there is a paucity of such studies in the management of panic disorder in older adults ( ages 55 and above ) . The purpose of this study was to gather pilot data in older patients with panic disorder to begin to assess the efficacy of two commonly-used antipanic medications , imipramine and alprazolam . Method : Twenty-five ( n = 25 ( 23 females ; 2 males ) ; 18 completers , 7 dropouts ) older panic disorder ( DSM-III-R ) patients ( age range = 55–73 ; mean = 61.24 ) were studied in an eight-week r and omized , parallel-groups , double-blind , placebo-controlled , flexible dose design . Outcome was assessed weekly by global change ratings ( Hamilton Anxiety and Depression Scales ; Physicians ' Global Impression ratings ) and panic diaries . Because of small sample size , we present data descriptively . Results : Subjects in active medication groups evidence d reductions in panic attacks and in levels of overall anxiety and depression . Therapeutic dosages were approximately half those commonly used in younger panic disorder patients . Conclusion : Our data suggest the comparable efficacy of alprazolam and imipramine in the short-term treatment of older adults with panic disorder . There is clearly the need for a larger scale placebo-controlled study , preferably comparing imipramine and /or alprazolam with one of the SSRIs , to substantiate our findings", " Forty‐one panic disorder patients receiving placebo were investigated in a double‐blind comparison of alprazolam , imipramine and placebo in panic disorder . A significantly higher drop‐out rate was found in the placebo group than in the active treatment groups , but placebo response was found in 34 % of the patients , defined as reduction of panic attacks to zero , and in 23 % , defined as a score of > 8 on the Physician Global Improvement Scale ( 0 10 points ) . Several predictors of response to placebo were found . The responders had fewer panic attacks than the nonrcsponders at baseline . They also reported less psychopathology and were less help‐seeking than the nonresponders . The implication s for psychopathology and possible response to psychotherapy among responders and nonresponders are discussed . It is hypothesized that the responders show more signs of realistic processing of internal and external stimuli and fewer signs of subjective distress than the nonresponders . Responders will therefore probably be more responsive to psychotherapy than nonresponders", "This study was design ed to explore the dose‐response relationship for clomipramine in patients with panic disorder , with or without agoraphobia . After 1 week of single‐blind placebo pretreatment , 180 such patients were assigned to a multicentre placebo‐controlled comparison of the effects of high and low doses of clomipramine , and were followed up for 8 weeks . In alleviating anxiety and panic disorder , both clomipramine doses were more efficacious than placebo for panic disorder and , to a lesser degree , for phobia . The lower dose was better tolerated and at least as effective as the higher dose , sometimes more so . These results indicate the clinical ly important possibility that low‐dose clomipramine is effective and well tolerated", "OBJECTIVE The authors assessed whether adding cognitive behavior therapy ( CBT ) to imipramine for patients with panic disorder decreased the severity of side effects and dropouts from side effects . METHOD Data were analyzed for 172 panic disorder patients who were r and omly assigned to receive imipramine alone , imipramine plus CBT , or placebo . Mixed-effects models were used to assess longitudinal differences among the treatment groups with respect to side effect burden and dropout rates during the acute , maintenance , and follow-up phases of treatment . RESULTS Patients treated with imipramine plus CBT experienced less severe fatigue/weakness , dry mouth , and sweating and had a lower rate of dropout due to side effects compared with those treated with imipramine only . CONCLUSIONS The addition of CBT to medication treatment with imipramine was associated with less severe side effects and fewer dropouts due to perceived side effects than treatment with imipramine alone", "BACKGROUND Both behavior-modification methods and antidepressants have proved to be effective in the treatment of agoraphobia . The authors examined the effects of clomipramine on agoraphobia in patients who failed to respond to exposure-based behavioral treatment . METHOD Eighteen patients with panic disorder with agoraphobia who had not responded to previous inpatient behavioral treatment were recruited to a 12-week , placebo-controlled , double-blind crossover study of clomipramine , at top doses of 150 mg/day for 3 weeks . The patients were assessed on measures of phobic avoidance , agoraphobic cognitions , panic , state and trait anxiety , subjective anxiety , and depression . RESULTS One patient dropped out of the study after 6 weeks . On most outcome measures , the 17 study completers had significantly ( p symptom scores at posttest in the active drug period than at posttest in the placebo period ; however , the clinical gains were modest . CONCLUSION The short-term efficacy of clomipramine for agoraphobic patients who failed to respond lastingly to behavioral treatment was demonstrated . It remains to be shown that clomipramine can lead to clinical ly significant and lasting benefits in these patients", "BACKGROUND Citalopram is a serotonin reuptake inhibitor which has been demonstrated to be highly selective and with a superior tolerability profile to the classical tricyclic antidepressants . This study was design ed to test whether there was any difference in efficacy in the management of panic disorder ( PD ) between citalopram and placebo . METHOD This was a double-blind , placebo and clomipramine controlled , parallel group eight-week study . A total of 475 patients with PD , with or without agoraphobia , were r and omised to treatment with either placebo , clomipramine 60 or 90 mg/day , or citalopram 10 or 15 mg/day , or 20 or 30 mg/day , or 40 or 60 mg/day . Doses were increased over the first three weeks , stabilised during the fourth week and fixed between weeks five and eight . RESULTS Treatment with citalopram at 20 or 30 mg , 40 or 60 mg and clomipramine were significantly superior to placebo , judged by the number of patients free of panic attacks in the week prior to the final assessment . All rating scales examined suggested that citalopram 20 or 30 mg was more effective than citalopram 40 or 60 mg . CONCLUSION The most advantageous benefit/risk ratio for the treatment of PD was associated with citalopram 20 or 30 mg/day", "BACKGROUND Panic disorder ( PD ) is generally regarded as a chronic condition with considerable variation in severity of symptoms . AIMS To describe the long-term outcome of naturalistically treated PD . METHODS Fifty-five out patients with PD , who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study . RESULTS Complete recovery ( no panic attacks and no longer on medication during the last 10 years ) was seen in 18 % of patients , and an additional 13 % recovered but were still on medication . Fifty-one percent experienced recurrent anxiety attacks whereas 18 % still met diagnostic criteria for PD . The incidence of agoraphobia decreased from 69 % to 20 % . Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission , although both groups reported improved daily functioning at follow-up . Maintenance medication was common . No benzodiazepine abuse was reported . CONCLUSION PD has a favourable outcome in a substantial proportion of patients . However , the illness is chronic and needs treatment . The short-term treatment given in the drug trial had no influence on the long-term outcome", "CONTEXT Panic disorder ( PD ) may be treated with drugs , psychosocial intervention , or both , but the relative and combined efficacies have not been evaluated in an unbiased fashion . OBJECTIVE To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo , whether one treatment is more effective than the other , and whether combined therapy is more effective than either therapy alone . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998 . PATIENTS A total of 312 patients with PD were included in the analysis . INTERVENTIONS Patients were r and omly assigned to receive imipramine , up to 300 mg/d , only ( n=83 ) ; cognitive-behavioral therapy ( CBT ) only ( n=77 ) ; placebo only ( n=24 ) ; CBT plus imipramine ( n=65 ) ; or CBT plus placebo ( n=63 ) . Patients were treated weekly for 3 months ( acute phase ) ; responders were then seen monthly for 6 months ( maintenance phase ) and then followed up for 6 months after treatment discontinuation . MAIN OUTCOME MEASURES Treatment response based on the Panic Disorder Severity Scale ( PDSS ) and the Clinical Global Impression Scale ( CGI ) by treatment group . RESULTS Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS ( response rates for the intent-to-treat [ ITT ] analysis , 45.8 % , 48.7 % , and 21.7 % ; P=.05 and P=.03 , respectively ) , but were not significantly different for the CGI ( 48 . 2 % , 53.9 % , and 37.5 % , respectively ) . After 6 months of maintenance , imipramine and CBT were significantly more effective than placebo for both the PDSS ( response rates , 37.8 % , 39.5 % , and 13.0 % , respectively ; P=.02 for both ) and the CGI ( 37.8 % , 42.1 % , and 13.0 % , respectively ) . Among responders , imipramine produced a response of higher quality . The acute response rate for the combined treatment was 60.3 % for the PDSS and 64.1 % for the CGI ; neither was significantly different from the other groups . The 6-month maintenance response rate for combined therapy was 57.1 % for the PDSS ( P=.04 vs CBT alone and P=.03 vs imipramine alone ) and 56.3 % for the CGI ( P=.03 vs imipramine alone ) , but not significantly better than CBT plus placebo in either analysis . Six months after treatment discontinuation , in the ITT analysis CGI response rates were 41.0 % for CBT plus placebo , 31.9 % for CBT alone , 19.7 % for imipramine alone , 13 % for placebo , and 26.3 % for CBT combined with imipramine . CONCLUSIONS Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance . Each treatment worked well immediately following treatment and during maintenance ; CBT appeared durable in follow-up . JAMA . 2000;283:2529 -", "BACKGROUND This 12-week , placebo-controlled study was carried out to compare the relative efficacy of paroxetine , clomipramine , and cognitive therapy in the treatment of DSM-III-R-defined panic disorder with or without agoraphobia . METHOD After a 3-week single-blind , placebo run-in period , 131 patients were r and omly assigned to receive double-blind medication or 12 sessions of cognitive therapy based on the model of Clark . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression scale , the Patient Global Evaluation , the Hamilton Rating Scale for Anxiety , the Marks-Sheehan Phobia Scale , the Montgomery-Asberg Depression Rating Scale , and the Sheehan Disability Scale . RESULTS Comparisons with placebo revealed significant superiority of paroxetine ( 20 - 60 mg/day ) and clomipramine ( 50 - 150 mg/day ) on nearly all outcome measures . On most measures , paroxetine also showed higher efficacy than cognitive therapy . With few exceptions , cognitive therapy did not differ significantly from placebo . The number of subjects becoming panic-free ( 66 % ) was higher and the onset of action was faster in the paroxetine-treated group . Treatment with cognitive therapy yielded the highest drop-out rate ( 26 % ) . CONCLUSION In this short-term study assessing treatment of panic disorder and agoraphobia , paroxetine and clomipramine were consistently superior to pill placebo , whereas cognitive therapy was superior on only a few measures", "In a double-blind , placebo-controlled trial comparing alprazolam and imipramine for panic disorder , serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication . Excluding these patients changed the results", "BACKGROUND Self-administered cognitive behavior therapy ( SCBT ) has been shown to be an effective alternative to therapist-delivered treatment for panic disorder ( PD ) . However , it is unknown whether combining SCBT and antidepressants can improve treatment . This trial evaluated the efficacy of SCBT and sertraline , alone or in combination , in PD . METHOD Patients ( n=251 ) were r and omized to 12 weeks of either placebo drug , placebo drug plus SCBT , sertraline , or sertraline plus SCBT . Those who improved after 12 weeks of acute treatment received treatment for an additional 12 weeks . Outcome measures included core PD symptoms ( panic attacks , anticipatory anxiety , agoraphobic avoidance ) , dysfunctional cognitions ( fear of bodily sensations , agoraphobic cognitions ) , disability , and clinical global impression of severity and improvement . Efficacy data were analyzed using general and generalized linear mixed models . RESULTS Primary analyses of trends over time revealed that sertraline/SCBT produced a significantly greater rate of decline in fear of bodily sensations compared to sertraline , placebo/SCBT and placebo . Trends in other outcomes were not significantly different over time . Secondary analyses of mean scores at week 12 revealed that sertraline/SCBT fared better on several outcomes than placebo , with improvement being maintained at the end of continuation treatment . Outcome did not differ between placebo and either sertraline monotherapy or placebo/SCBT . Moreover , few differences emerged between the active interventions . CONCLUSIONS This trial suggests that sertraline combined with SCBT may be an effective treatment for PD . The study could not confirm the efficacy of sertraline monotherapy or SCBT without concomitant medication or therapist assistance in the treatment of PD", "The Cross-National Collaborative Panic Study , Phase Two , compared alprazolam with imipramine and with placebo in a sample of 1168 r and omly assigned subjects . The study , conducted at 12 centres , assessed clinical change over eight weeks of double-blind drug treatment . Improvement occurred with alprazolam by week 1 and 2 , and with imipramine by week 4 . By the end of week 8 , however , the effects of the two active drugs were similar to each other , and both were superior to placebo for most outcome measures", "BACKGROUND Venlafaxine extended-release ( ER ) has proven efficacy in the treatment of anxiety symptoms in major depression , generalised anxiety disorder and social anxiety disorder . AIMS To evaluate the efficacy , safety and tolerability of venlafaxine ER in treating panic disorder . METHOD Adult out- patients ( n=361 ) with panic disorder were r and omly assigned to receive venlafaxine ER ( 75 - 225 mg/day ) or placebo for up to 10 weeks in a double-blind study . RESULTS Venlafaxine ER was not associated with a greater proportion of patients free from full-symptom panic attacks at the final on-therapy evaluation , but was associated with lower mean panic attack frequency and a higher proportion free from limited-symptom panic attacks , higher response and remission rates , and improvements in anticipatory anxiety , fear and avoidance . Adverse events were comparable with those of the drug in depression and anxiety disorders . CONCLUSIONS Venlafaxine ER seems to be effective and well tolerated in the short-term treatment of panic disorder", " Forty-seven patients meeting DSM-III-R criteria for panic disorder with agoraphobia ( PAG ) were assessed by the Minnesota Multiphasic Personality Inventory ( MMPI ) at baseline and after 8 weeks of treatment with imipramine , clomipramine and placebo . At pre-treatment patients had higher MMPI scores than the local normative data , the highest scores being for depression , hypochondria and hysteria . At week 8 the scores of most MMPI scales were significantly reduced . In addition , patients who showed clinical improvement had pre- and post-treatment scores lower than the unimproved patients . The results suggest that the abnormal MMPI profile found in PAG patients reflects the clinical state and that personality pathology relates to treatment outcome . The reduction in MMPI scores was associated with response to active treatment . We conclude that therapeutic interventions that successfully reduce PAG symptoms also modify personality scores", "Jitteriness appears to be a specific side effect of tricyclic antidepressant treatment in panic disorder patients . In addition , the patients with jitteriness have lower serum iron levels compared to those that do not develop jitteriness ( p = 0.01 )", "A comparison of safety , and efficiency of Alprazolam , Imipramine , and placebo in the treatment of panic disorder shows that both active drugs are significantly superior to placebo as regards therapeutic effectiveness . On a 77 patient sample , 62 completed an 8-week treatment , and 66 were considered as \" assessable \" for efficiency results after completing a 3-week treatment . Significantly , more placebo-treated patients than either Alprazolam , or Imipramine-treated patients dropped out trial , while the number of panic attacks was significantly reduced in both Alprazolam- , and Imipramine-treated groups . When trial was over , 96 % of patients in Alprazolam group , and 95 % of patients in Imipramine group were free from panic attacks , if compared to 65 % in the placebo group . Generally speaking , drugs were well tolerated , and no serious adverse effects or life-threatening events were observed", "Serotonergic mechanisms have been implicated in panic disorder , and several preliminary studies suggest that fluvoxamine , a selective serotonin reuptake inhibitor ( SSRI ) , is helpful in its treatment . This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia . Efficacy assessment s included a Daily Panic Attack Inventory , the Sheehan Disability Scale , the Clinical Anxiety Scale and the Clinical Global Impression Scale . When compared with the placebo , fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress . Significant improvement was evident as early as week 1 for some panic variables . Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action", "OBJECTIVE To evaluate the efficacy , safety , and tolerability of venlafaxine extended release ( ER ) in short-term treatment of panic disorder . METHOD In this multicenter , double-blind study , conducted from April 2001 to December 2002 , 343 adult out patients who met criteria for panic disorder ( with and without agoraphobia ) according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , were r and omly assigned to flexible-dose venlafaxine ER ( 75 - 225 mg/d ) or placebo for 10 weeks ( N = 155 per group , intent-to-treat population ) . The primary outcome measure was the percentage of panic-free patients as assessed using the Sheehan Panic and Anticipatory Anxiety Scale . Key secondary measures included the Panic Disorder Severity Scale ( PDSS ) score and Clinical Global Impressions-Improvement ( CGI-I ) scale response ( score = 1 or 2 ) . Last-observation-carried-forward data were analyzed , and statistical significance was set at p full-symptom panic attacks was 52 % in the venlafaxine ER group and 43 % in the placebo group ( p = .11 ) . Mean change from baseline in PDSS total score was significantly ( p = .006 ) greater for the venlafaxine ER group ( -9.3 ) than for the placebo group ( -7.5 ) , and significantly ( p = .03 ) more venlafaxine ER-treated patients achieved CGI-I response ( 71 % ) than did those receiving placebo ( 59 % ) at week 10 . Treatment with venlafaxine ER was generally safe and well tolerated . Adverse events were the primary or secondary cause for discontinuation for 7 placebo patients ( 4 % ) and 12 venlafaxine ER patients ( 7 % ) . CONCLUSIONS Venlafaxine ER appears to be effective , safe , and well tolerated in short-term treatment of panic disorder , although the results fell just short of significance on the primary outcome measure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00038896", "BACKGROUND Tricyclic antidepressants and selective serotonin reuptake inhibitors ( SSRIs ) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder . The introduction of SSRIs has enabled a greater underst and ing of the role of serotonin in the etiology of panic disorder ; however , the role of norepinephrine has been more challenging to ascertain . The aim of this study was to determine the efficacy and tolerability of reboxetine , a novel selective norepinephrine reuptake inhibitor , in patients with panic disorder with and without agoraphobia . METHOD Eighty-two patients ( aged 18 - 65 years ) with DSM-III-R panic disorder , with or without agoraphobia , were r and omly assigned to receive 6 to 8 mg/day of reboxetine ( 42 patients ) or placebo ( 40 patients ) for 8 weeks in this placebo-controlled , parallel-group , double-blind clinical trial . RESULTS Of the 82 patients enrolled in the trial , 75 were considered in the analysis ( 37 patients in the reboxetine group and 38 patients in the placebo group ) . At last assessment , there was a significant reduction in the mean number of panic attacks ( range , 9.3 - 1.2 ) and phobic symptoms ( range , 8.1 - 3.2 ) in the reboxetine group compared with the placebo group ( ranges , 8.5 - 5.8 and 7.7 - 5.2 , respectively ; p Hamilton Rating Scale for Depression , Hopkins Symptom Checklist-90 , and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group . Adverse events reported more frequently with reboxetine than placebo included dry mouth ( 36 % vs. 16 % ) , constipation ( 27 % vs. 22 % ) , and insomnia ( 26 % vs. 22 % ) . CONCLUSION Reboxetine was effective and well tolerated in the treatment of panic disorder", "Summary The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study ( n=1134 patients ) ; in this double blind r and omized trial alprazolam , imipramine and placebo were compared during an 8-week treatment period . Patients with extensive avoidance behaviour ( agoraphobia ) had the most profit from the active drugs . Counter expectancy these specific drug effects were most pronounced in avoidance behaviour . Active drugs ( in particular imipramine ) were especially more effective than placebo if the patients presented with associated avoidance behaviour . The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder", " Buspirone was compared with imipramine and placebo in the treatment of panic disorder in an 8-week , double-blind controlled study of 52 r and omly assigned patients . The side effect profile of buspirone was less disruptive than that of imipramine . Buspirone was not significantly superior to placebo in its antipanic or anxiolytic effects in panic disorder patients", "The aim of this 12‐week , double‐blind , parallel group , placebo‐controlled study was to compare paroxetine with clomipramine in 367 patients with DSM‐III‐R defined panic disorder . Efficacy assessment s included the daily panic attack diary , the Clinical Global Impression Scale , the Hamilton Anxiety Rating Scale , the Marks Sheehan Phobia Scale and the Sheehan Disability Scale . Paroxetine produced significant improvements compared with placebo in various measurements of panic attack frequency , and was as effective as clomipramine . However , paroxetine appeared to have a more rapid onset of action than clomipramine in reducing the number of panic attacks to zero . There was an equivalent improvement with both paroxetine and clomipramine in the supportive efficacy variables which assessed associated aspects of therapeutic improvement . Significantly more adverse effects were reported in the clomipramine group compared with the paroxetine group , while there was no difference between the paroxetine and placebo groups", "BACKGROUND The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult out patients with panic disorder with or without agoraphobia . METHOD Patients in this double-blind , parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram ( 10 or 15 mg/day , 20 or 30 mg/day , or 40 or 60 mg/day ) , 1 dosage range of clomipramine ( 60 or 90 mg/day ) , or placebo . After the completed 8-week acute treatment period , the eligible patients could continue the treatment for up to 1 year . Of the 475 patients who were r and omly assigned for the short-term trial , 279 agreed to continue double-blind treatment at their assigned doses . The primary efficacy measure used was the Clinical Anxiety Scale panic attack item , and the response was defined as no panic attacks ( score of 0 or 1 ) . The other key measures used were the Physician 's Global Improvement Scale , the Patient 's Global Improvement Scale , and the Hamilton Rating Scale for Anxiety ( HAM-A ) . RESULTS In all drug-treated groups , except the group receiving the lowest citalopram dose , the treatment outcome was generally better than with placebo . As determined by a life table analysis of response , the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo ( p citalopram 20 or 30 mg/day demonstrating the best response . Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up . Analysis of the difference in the number of patients in different treatment groups remaining in the study ( perhaps the best measure of long-term efficacy ) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients ( p HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients . All treatment groups showed no new or exceptional adverse event clusters . CONCLUSION Citalopram in the dosage range of 20 to 60 mg/day is effective , well tolerated , and safe in the long-term treatment of patients who have panic disorder", "One of the core problems in clinical research is the detection of early changes in target symptoms that predict future therapeutic outcome . To analyze potential predictors of outcome , data of a multicenter study on patients with panic disorder were used . A total of 1010 patients were r and omly allocated either to alprazolam , imipramine or placebo treatment . Early improvement in the number of spontaneous panic attacks within the first week of treatment predicted outcome exclusively in the alprazolam group . In contrast , placebo responders and nonresponders were differentiated by early changes in anticipatory anxiety intensity . For tricyclic antidepressants such as imipramine an evaluation period of more than one week is required to allow conclusions about outcome", "BACKGROUND This study compared the efficacy and safety of sertraline to placebo in treating panic disorder . METHOD 178 out- patients with panic disorder who exhibited at least four panic attacks during the four weeks prior to screening and three during the two weeks of lead-in were r and omly assigned to 12 weeks of double-blind treatment with sertraline ( 50 , 100 or 200 mg ) or placebo . RESULTS Sertraline was superior to placebo in reducing the number of panic attacks , situational attacks , unexpected attacks , limited symptom attacks , and time spent worrying ( all P Hamilton Anxiety Scale ( P serious adverse events were associated with sertraline . No dose relationship was found for adverse events ; overall drop-out rates were not different for sertraline or placebo , although more sertraline-treated subjects discontinued for adverse events , typically early in the study . Only dry mouth and ejaculation failure ( primarily ejaculation delay ) were associated significantly with sertraline . CONCLUSIONS Sertraline was effective and safe in reducing panic attacks . Higher doses were no more effective than the 50 mg dose", "OBJECTIVE This study was design ed to determine the minimum paroxetine dose effective for treating panic disorder . METHOD Of 425 patients with DSM-III-R panic disorder with or without agoraphobia who underwent a 2-week drug-free screening period , 278 patients were r and omly assigned to double-blind treatment with a 10-week course of placebo or paroxetine at a dose of 10 , 20 , or 40 mg/day . RESULTS At 40 mg/day , paroxetine was superior to placebo across the majority of outcome measures . Despite a mean of 9.5 to 11.6 full panic attacks during the screening period , 86.0 % of the patients taking 40 mg of paroxetine , 65.2 % of those taking 20 mg , 67.4 % of those taking 10 mg , and 50.0 % of the placebo-treated patients were free of full panic attacks during the 2 weeks ending at week 10 . The 40-mg paroxetine group experienced significantly greater global improvement than the placebo group and significantly greater improvement in frequency of full and limited-symptom panic attacks , intensity of full panic attacks , phobic fear , anxiety , and depressive symptoms , usually evident by week 4 . All doses of paroxetine were well tolerated , and adverse effects were consistent with those associated with selective serotonin reuptake inhibitors . CONCLUSIONS Paroxetine is an effective and well-tolerated short-term treatment of panic disorder . The minimum dose demonstrated to be significantly superior to placebo was 40 mg/day , although some patients did respond at lower doses", "BACKGROUND This study compared the efficacy and tolerability of paroxetine with placebo in the treatment of panic disorder . METHOD After three weeks of placebo , patients received 12 weeks of treatment with paroxetine ( 20 , 40 , or 60 mg ) or placebo , and finally two weeks of placebo . Dosages were adjusted according to efficacy and tolerability . St and ardised cognitive therapy was given to all patients . The primary measure of outcome was reduction in the number of panic attacks . RESULTS Analysis of the results showed statistically significant differences in favour of paroxetine between the two treatment groups in two out of the three primary measures of outcome , i.e. 50 % reduction in total number of panic attacks and number of panic attacks reduced to one or zero over the study period . For the third measure of outcome , the mean change in the total number of attacks from baseline , there was a positive trend in favour of paroxetine . The results of the primary measures of outcome were strongly supported by the results of the secondary efficacy measures of outcome . In addition , paroxetine , at all doses , was very well tolerated . CONCLUSION Paroxetine plus cognitive therapy was significantly more effective than placebo plus cognitive therapy in the treatment of panic disorder" ]	41183f24-06ff-11f0-808a-c43d1ab1c353
Little is known about the dimensions of osteoporosis prevention programs essential to changing health behaviors . The purpose of this review was to determine the impact of select characteristics of structured osteoporosis prevention programs on calcium intake in women . This systematic review included 12 experimental and quasi-experimental studies conducted internationally with adult women participants . Studies were more likely to demonstrate differences when they were conducted outside the U.W. ; participants had lower baseline calcium intake ; and interventions were multi-dimensional and included factual information , skill training , and social contact delivered dynamically over time . The results document extensive variability across participants , programs , and measures . There is a need to document the source ( total and sub-total ) of calcium intake , to provide the necessary data to calculate effect sizes to enable comparison across studies , and to identify those moderating factors ( such as menopausal status ) that affect the ability to determine differences between sub-groups . Results indicate health behavior change is more likely to occur when patient-centered interventions design ed to increase knowledge and health beliefs , skills and abilities , and social facilitation are delivered over time . There is an urgent need for the development and testing of new health behavior change theories , prevention programs , and delivery media to support and complement health care providers in the prevention and management of this common , debilitating condition	[ "OBJECTIVE To examine the effect of community-based nutrition education intervention on calcium intake and bone mass in Vietnamese postmenopausal women . DESIGN A controlled trial was conducted in two groups as intervention and control . The intervention group was given nutrition education during 18 months to improve calcium intake , while the control subjects had the usual diet . Calcium intake and bone mass were evaluated every 6 months . Bone mass was assessed by speed of sound ( SOS ) at calcaneus , referred to as quantitative ultrasound measurement . Anthropometric indices and serum parathyroid hormone ( PTH ) were determined at baseline and at the end of intervention . SETTING Two rural communes of Hai Duong province located in the Red River Delta in Vietnam . SUBJECTS A total of 140 women aged 55 - 65 years , who were more than 5 years postmenopausal and with low calcium intake ( After 18 months of intervention , 108 women completed the study . RESULTS Calcium intake in the intervention group had increased significantly ( P SOS values were not changed significantly in the intervention subjects while it decreased significantly by 0.5 % in the controls ( P serum PTH by 12 % ( P serum PTH by 32 % ( P Nutrition education intervention was effective in improving calcium intake and retarding bone loss in the studied subjects", "Changes in FSH and estradiol ( E2 ) across the menopausal transition are clearly not linear . The present study utilizes data from 204 women who completed the 13-year prospect i ve Melbourne Women 's Midlife Health Project . E2 , FSH , symptoms , self-rated health , mood , sexual function and coronary heart disease ( CHD ) risk were measured longitudinally . We presumed an s-shaped curve for each hormone and estimated five parameters for each hormone curve for each woman : baseline , final value , range , slope at inflexion point and age at inflexion point . These parameters were found to adequately estimate the curve for each hormone . The median age of transition observed for E2 occurs > 1 year later than the median age of transition observed for FSH . FSH parameters did not affect any of the health outcomes analysed . Hot flushes , night sweats , sleeping problems , vaginal dryness and to a lesser extent self-rated health were highly significantly associated with E2 range and slope . Sexual response and CHD risk were highly significantly associated with final E2 level ( post-menopausally ) . These findings have clinical relevance in identifying which symptoms will be triggered by steep transitions of E2 such as sudden withdrawal and which health parameters may require a maintenance level of E2", "Background Limited information is available on ways to influence osteoporosis risk in premenopausal women . This study tested four hypotheses regarding the effects of individualized bone density ( BMD ) feedback and different educational interventions on osteoporosis preventive behavior and BMD in pre-menopausal women , namely : that women are more likely to change calcium intake and physical activity if their BMD is low ; that group education will be more efficacious at changing behavior than an information leaflet ; that BMD feedback and group education have independent effects on behavior and BMD ; and , that women who improve their physical activity or calcium intake will have a change in bone mass over 2 years that is better than those who do not alter their behavior . Methods We performed a 2-year r and omized controlled trial of BMD feedback according to T-score and either an osteoporosis information leaflet or small group education in a population -based r and om sample of 470 healthy women aged 25–44 years ( response rate 64 % ) . Main outcome measures were dietary calcium intake , calcium supplement use , smoking behavior , physical activity , endurance fitness , lower limb strength and BMD . We used paired t-tests , one-way ANOVA and linear regression techniques for data analysis . Results Women who had feedback of low BMD had a greater increase in femoral neck BMD than those with normal BMD ( 1.6 % p.a . vs. 0.7 % p.a . , p = 0.0001 ) , but there was no difference in lumbar spine BMD change between these groups ( 0.1 % p.a . vs. 0.08 % p.a . , p = 0.9 ) . Both educational interventions had similar increases in femoral neck BMD ( Leaflet = + 1.0 % p.a . , Osteoporosis self-management course = + 1.3 % p.a . , p = 0.4 ) . Femoral neck BMD change was only significantly associated with starting calcium supplements ( 1.3 % p.a , 95%CI + 0.49 , + 2.17 ) and persistent self-reported change in physical activity levels ( 0.7 % p.a . , 95%CI + 0.22 , + 1.22 ) . Conclusion Individualized BMD feedback combined with a minimal educational intervention is effective at increasing hip but not spine bone density in premenopausal women . The changes in behavior through which this was mediated are potentially important in the prevention of other diseases , thus measuring BMD at a young age may have substantial public health benefits , particularly if these changes are sustained", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "OBJECTIVE The aim of the current study was to examine whether a diet rich in dairy products followed by a nutrition education program for the prevention of osteoporosis could have any adverse effect on certain cardiovascular disease ( CVD ) risk factors over a 5-month intervention period . METHODS A total sample of 82 women ( 55 - 65 years old ) was r and omized to a dietary intervention group ( IG : n=42 ) , attending biweekly nutrition education program and provided with low-fat , fortified dairy products and to a control group ( CG : n=40 ) . Changes in dietary , biochemical and clinical indices related to CVD were determined at the end of the 5-month intervention period . RESULTS The IG was found to have a higher decrease in the percentage of energy intake derived from total fat and a higher increase in the intake of calcium , phosphorus , magnesium and potassium compared to the CG ( p BMI ( 0.7+/-0.1 versus 1.4+/-0.2 Kg/m(2 ) , p=0.011 ) and systolic blood pressure ( SBP ) ( 2.5+/-2.9 versus 7.8+/-2.2 mmHg , p=0.040 ) and a higher decrease in serum total cholesterol ( -5.2+/-3.3 versus 6.9+/-5.1 mg/dl , p=0.042 ) and LDL-cholesterol levels ( -20.0+/-2.6 versus -12.4+/-4.2 mg/dl , p=0.034 ) compared to the CG . CONCLUSIONS The findings of the current study indicate that a dietary intervention aim ing to minimize the risk for osteoporosis did not have any adverse effects on CVD risk factors . On the contrary , it has induced favourable changes in BMI , serum lipids and SBP", "In 2001 , the Stages of Reproductive Aging Workshop ( STRAW ) proposed bleeding and endocrine criteria for defining the early and late menopausal transition stages . Based on expert consensus , STRAW recommended a shorter interval of amenorrhea than the commonly used 90-day amenorrhea criteria for late transition and a > 7-day change in cycle length for early transition . The ReSTAGE collaboration used prospect i ve menstrual calendar data from four cohorts ( TREMIN , Melbourne Women 's Midlife Health Project , Seattle Midlife Women 's Health Study , and Study of Women 's Health Across the Nation ) to quantitatively evaluate STRAW 's recommendations . This empirical assessment supported the STRAW recommendations that ( 1 ) ≥60 days of amenorrhea be used to define the late menopausal transition and ( 2 ) that early transition is consistent with a persistent 7 or more day difference in length of consecutive cycles . Serum follicle stimulating hormone ( FSH ) values ≥40 IU/l was an independent marker of the transition and , when occurring together with a bleeding marker , increased prediction of final menstrual period . Such a FSH criterion could be incorporated into the STRAW paradigm to facilitate prediction of proximity of the final menstrual period", "Objective To evaluate the effectiveness of an educational video on osteoporosis at increasing knowledge and preventive health behaviors . Design A total of 195 women between 35 and 80 years of age without documented osteopenia or osteoporosis , who presented for a gynecological examination in an outpatient setting , were enrolled . Of this number , 98 women were r and omly assigned to the intervention group that viewed the video before their office visit , and 97 women were assigned to a control group and saw their physician in a routine manner . After their visit , all participants answered a question naire that assessed their knowledge of osteoporosis and baseline health-related behaviors . Three months later , a follow-up question naire was mailed to participants , eliciting whether preventive behavior had commenced . Frequencies were compared using the Fisher exact test ( 2-tailed ) . Continuous variables were analyzed using the Student 's t test . Results The two groups had no statistically significant differences in demographics . The intervention group scored a mean of 92 % compared with a mean of 80 % in the control group on the initial osteoporosis assessment question naire ( P taking calcium supplements ( 26.5 % v 4.9 % ; P taking vitamin D supplements ( 20.6 % v 6.6 % ; P = 0.02 ) , started a program of weight-bearing exercise ( 13.3 % v 1.7 % ; P = 0.03 ) , and started hormone therapy ( 8 % v 1 % ; P = 0.04 ) . Conclusion The use of an educational video on osteoporosis seems to improve patient knowledge and may positively impact health-related behaviors", "Objective : There has been controversy about the relative effects on various health outcomes of hormonal , psychosocial , and lifestyle changes during the menopausal transition . In previous studies the risk factors for one particular health endpoint have been analyzed separately . Separate analyses do not provide an overall view of the relationships between all the variables or the relative importance of different factors . Thus , the objective of this study was to provide an overall analysis of the influence of hormonal changes during the menopausal transition on a range of health outcomes while simultaneously considering all the available predictors and all the endpoints and to test the hypothesis that prior health status predicts current health status . Design : This was a 9-year prospect i ve observational study of 438 Australian-born women , who at baseline were aged 45 to 55 years and had menstruated in the prior 3 months . Interviews were conducted and fasting blood and physical measurements were performed annually . Results : Main outcome measures were hormone levels , sociodemographic variables , attitudes and lifestyle variables , self-rated health and well-being , bothersome symptoms , coronary heart disease risk , bone mineral density , and sexuality . Data from 336 women , 77 % of the original sample , were analyzed . Statistical modeling using structural equations showed that for all health endpoints , the prior level of that variable was the most important predictor . Declining levels of estradiol during the menopausal transition affected certain health outcomes : bone mineral density , coronary heart disease risk , vasomotor symptoms , vaginal dryness , and sexual response . Well-being is negatively affected by symptoms , hassles , and stress . Exercise has beneficial effects on hot flushes , well-being , body mass index , and coronary heart disease risk . Relationship factors and mood affect sexual response . Conclusions : This observational study provides a conceptual data -based framework for underst and ing changes in women 's health during the natural menopausal transition", "PURPOSE The purpose of this pilot study was to determine if tailored nursing interventions based on personal knowledge of bone mineral density from a dual-energy x-ray absorptiometry cause increases in knowledge of osteoporosis , health beliefs , or osteoporosis-prevention behaviors in postmenopausal women 50–65 years of age , 6 months after the intervention . METHOD The design for this pilot study was a two group quasi-experimental design . The treatment group received a tailored intervention ; the control group did not . Outcome data were gathered at 6 months after dual-energy x-ray absorptiometry . The tailored intervention was design ed and given to each woman via telephone using her dual-energy x-ray absorptiometry results and osteoporosis question naire data that addressed her knowledge of osteoporosis and osteoporosis-prevention behaviors of calcium intake , exercise , smoking , and alcohol use . A written mailed copy of the intervention followed the telephone interview . Six months after the intervention , the women were mailed another osteoporosis question naire to determine if the tailored intervention made a difference in the outcome variables . SAMPLE A total 124 women between the ages of 50 and 65 ( 101 control , 23 treatment ) comprised the sample . RESULTS There was no difference in knowledge between groups . On the average , there were significantly more perceived barriers to calcium in the tailored group ( mean = 13.48 ) than in the nontailored group ( mean = 11.55 ) ( t = 2.147 ; df = 122 ; p = .034 ) . There were significantly more perceived barriers to exercise in the tailored group ( mean = 14.39 ) than in the nontailored group ( mean = 12.21 ) ( t = .144 ; df = 122 ; p = .034 ) . Daily calcium intake increased in both the tailored and the nontailored groups . The tailored intervention increased women 's daily calcium intake from 614.28 to 1039.10 mg ( t = −2.896 ; df = 22 ; p = .008 ) . The nontailored group daily calcium intake increased from 587.91 to 916.30 mg ( t = −3.541 ; df = 100 ; p = .001 ) ; there was no significant difference between the groups . Weight-bearing exercise behaviors decreased from 96.04 minutes to 59.2 minutes in the tailored group but increased slightly in the nontailored group from 81.47 to 87.26 minutes of exercise . CONCLUSION Tailored interventions increased women 's perceived barriers to calcium and exercise . Both groups increased calcium intake . The mixed findings of increased perception of barriers to calcium and exercise and decreased exercise behaviors indicate the need for further study . This important intervention has implication s for orthopaedic nurses and healthcare professionals involved in health promotion and prevention of osteoporosis", "Chinese-American women have a high risk of osteoporosis . However , their calcium intake has been reported previously as considerably below the Dietary Reference Intake . Increasing consumption of calcium-rich foods , many of which are also fortified with vitamin D , is a safe way to increase their calcium and vitamin D intake . This study 's objective was to pilot-test an intervention to help Chinese-American women incorporate calcium-rich foods into their diet . This intervention was evaluated using a quasi-experimental study with a nested design and pre- , immediate post- , and 3-month follow-up assessment s. Calcium and vitamin D intake , Theory of Planned Behavior constructs , and knowledge were measured at three time points . First-generation Chinese-American mothers between 35 and 55 years old ( n=141 ) were recruited from six weekend Chinese schools . Three Chinese schools each were r and omly assigned to the experimental ( n=71 ) or control group ( n=70 ) . The experimental group received a free heel scan and six weekly interactive lessons design ed based on the Theory of Planned Behavior . The control group received six weekly nonrelated financial lessons by mail . Changes for each measure were assessed by linear mixed model with repeated measures adjusted for confounding variables . Compared to the control group , the experimental group improved all measures considerably , except two subjective norm constructs ( normative belief and motivation to comply ) at post- assessment s. The experimental group significantly increased its baseline calcium ( t=7.898 , P vitamin D intake ( t=6.609 ; P dietary calcium and vitamin D intake of Chinese-American women", "Purpose . This study examined the effects of brief written educational material s on osteoporosis-related knowledge , beliefs , and behaviors . The study also examined whether observed effects varied as a function of one 's stage in the pre caution adoption process . Design . The study used an experimental research design . Setting . Participants were identified from North Carolina driver 's license records . Subjects . Of the 1476 women in the initial sample , 536 ( 36.3 % ) enrolled in the study and 307 completed all follow-up assessment s. Intervention . Participants were r and omly assigned to one of four groups . One group received an information packet containing general information about osteoporosis . One group received an action plan packet containing instructions on how to increase one 's level of exercise and calcium intake . One group received both packets . The final group received neither packet . Measures . Primary study variables were beliefs related to osteoporosis , calcium , and exercise ; osteoporosis knowledge ; calcium and exercise stage ; calcium intake ; and exercise level . Results . Overall , receipt of the information packet was associated with changes in knowledge and beliefs ( F[18,283 ] = 2.11 , p behavior were observed . Conclusions . These findings suggest that brief written educational material s can facilitate knowledge and belief change but that they do not promote behavior change . The generalizability of these findings is limited by the low study response rate", "Purpose . This study evaluated whether a combined behavioral and dietary intervention would affect young women 's calcium intake and bone mineral content ( BMC ) . Design . The design was a two by three mixed design with one between-subjects factor ( treatment vs. control ) and one within-subjects factor ( time — baseline , 3-month , and 6-month ) . Setting . The study was conducted in a university setting in Memphis , Tennessee . Participants . A total of 80 premenopausal women ( ages 18 to 30 ) with low baseline calcium intake ( were included in the analyses . There were 40 women in the treatment group and 40 women in the control group . Measures . Hertzler and Frary 's rapid assessment question naire was employed to evaluate calcium intake , and dual-energy x-ray absorptiometry ( DEXA ) was employed to assess BMC . Results . Repeated measures analysis of variance ( RM ANOVA ) was employed to analyze results . Results indicated that women in the treatment group made greater increases in total calcium intake and supplemental calcium than women in the control group and that all women made significant increases in dietary calcium intake . Additionally , analyses of BMC revealed that women in the treatment group did not experience significant changes in total BMC , and women in the control group experienced significant losses in total BMC . Conclusions . In the current study , women were losing BMC , and the women who made the largest increases in calcium intake were able to retard this bone loss . There is increasing evidence that dietary calcium intake in young people is extremely low , and the results of the current study highlight the need for much more intensive evaluations investigating the factors that are positively associated with premenopausal bone mineral change" ]	41183fb0-06ff-11f0-808a-c43d1ab1c353
Background H and grip strength ( HGS ) is used for the diagnosis of sarcopenia and frailty . Several factors have been shown to influence HGS values during measurement . Therefore , variations in the protocol s used to assess HGS , as part of the diagnosis of sarcopenia and frailty , may lead to the identification of different individuals with low HGS , introducing bias . The aim of this systematic review is to gather all the relevant studies that measured HGS to diagnose sarcopenia and frailty and to identify the differences between the protocol s used . Methods A systematic review was carried out following the recommendations of The Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) Statement . PubMed and Web of Science were systematic ally search ed , until August 16 , 2016 . The evidence regarding HGS measurement protocol s used to diagnose sarcopenia and frailty was summarised and the most recent protocol s regarding the procedure were compared . Results From the described search 4393 articles were identified . Seventy-two studies were included in this systematic review , in which 37 referred to sarcopenia articles , 33 to frailty and two evaluated both conditions . Most studies presented limited information regarding the protocol s used . Conclusions The majority of the studies included did not describe a complete procedure of HGS measurement . The high heterogeneity between the protocol s used , in sarcopenia and frailty studies , create an enormous difficulty in drawing comparative conclusions among them	[ "BACKGROUND A st and ard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults . However , the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain . METHODS To determine whether a st and ard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index ( BMI ) , we ascertained frailty status in a cohort of 6724 women > or=69 years and followed them prospect ively for incident falls , fractures , and mortality . Frailty was defined by the presence of three or more of the following criteria : unintentional weight loss , weakness , self-reported poor energy , slow walking speed , and low physical activity . Incident recurrent falls were defined as at least two falls during the subsequent year . Incident fractures ( confirmed with x-ray reports ) , including hip fractures , and deaths were ascertained during an average of 9 years of follow-up . RESULTS After controlling for multiple confounders such as age , health status , medical conditions , functional status , depressive symptoms , cognitive function , and bone mineral density , frail women were subsequently at increased risk of recurrent falls ( multivariate odds ratio=1.38 , 95 % confidence interval [ CI ] , 1.02 - 1.88 ) , hip fracture ( multivariate hazards ratio [MHR]=1.40 , 95 % CI , 1.03 - 1.90 ) , any nonspine fracture ( MHR=1.25 , 95 % CI , 1.05 - 1.49 ) , and death ( MHR=1.82 , 95 % CI , 1.56 - 2.13 ) . The associations between frailty and these outcomes persisted among women > or=80 years . In addition , associations between frailty and an increased risk of falls , fracture , and mortality were consistently observed across categories of BMI , including BMI > or=30 kg/m2 . CONCLUSION Frailty is an independent predictor of adverse health outcomes in older women , including very elderly women and older obese women", "OBJECTIVES To define frailty using simple indicators ; to identify risk factors for frailty as targets for prevention ; and to investigate the predictive validity of this frailty classification for death , hospitalization , hip fracture , and activity of daily living ( ADL ) disability . DESIGN Prospect i ve study , the Women 's Health Initiative Observational Study . SETTING Forty U.S. clinical centers . PARTICIPANTS Forty thous and six hundred fifty-seven women aged 65 to 79 at baseline . MEASUREMENTS Components of frailty included self-reported muscle weakness/impaired walking , exhaustion , low physical activity , and unintended weight loss between baseline and 3 years of follow-up . Death , hip fractures , ADL disability , and hospitalizations were ascertained during an average of 5.9 years of follow-up . RESULTS Baseline frailty was classified in 16.3 % of participants , and incident frailty at 3-years was 14.8 % . Older age , chronic conditions , smoking , and depressive symptom score were positively associated with incident frailty , whereas income , moderate alcohol use , living alone , and self-reported health were inversely associated . Being underweight , overweight , or obese all carried significantly higher risk of frailty than normal weight . Baseline frailty independently predicted risk of death ( hazard ratio (HR)=1.71 , 95 % confidence interval (CI)=1.48 - 1.97 ) , hip fracture ( HR=1.57 , 95 % CI=1.11 - 2.20 ) , ADL disability ( odds ratio (OR)=3.15 , 95 % CI=2.47 - 4.02 ) , and hospitalizations ( OR=1.95 , 95 % CI=1.72 - 2.22 ) after adjustment for demographic characteristics , health behaviors , disability , and comorbid conditions . CONCLUSION These results support the robustness of the concept of frailty as a geriatric syndrome that predicts several poor outcomes in older women . Underweight , obesity , smoking , and depressive symptoms are strongly associated with the development of frailty and represent important targets for prevention", "This study investigates which position ( grip span ) on the st and ard grip dynamometer results in maximum grip strength . Our None hypotheses included ( 1 ) no optimal grip span exists for measuring grip strength and ( 2 ) optimal grip span is unrelated to h and size . We also intended to derive a simple mathematical algorithm to adapt grip span to h and size . Seventy healthy subjects ( 40 women/30 men ; mean age , 40 years ; range ; 20 - 80 years ) free of upper-limb lesions were evaluated . Each h and was r and omly tested on 10 occasions using 5 different grip spans . Our findings showed that ( 1 ) optimal grip span was identified for both genders and ( 2 ) h and size and optimal grip span correlated in women but not in men . When measuring h and grip strength in women , h and size must be taken into consideration . We provide a mathematical equation ( y = x/5 + 1.5 cm ) to adapt optimal grip span ( y ) to h and size ( x ) in women . In adult men , optimal grip span can be set at a fixed value ( 5.5 cm )", "OBJECTIVE To compare clinical characteristics of sarcopenia defined by the International Working Group on Sarcopenia ( IWGS ) and European Working Group on Sarcopenia in Older People ( EWGSOP ) criteria among older people in Taiwan . DESIGN A prospect i ve population -based community study . SETTING I-Lan County of Taiwan . PARTICIPANTS A total of 100 young healthy volunteers and 408 elderly people . INTERVENTION None . MEASUREMENTS Anthropometry , skeletal muscle mass measured by dual x-ray absorptiometry , relative appendicular skeletal muscle index ( RASM ) , percentage skeletal muscle index ( SMI ) , 6-meter walking speed , and h and grip strength . RESULTS The prevalence of sarcopenia was 5.8 % to 14.9 % in men and 4.1 % to 16.6 % in women according to IWGS and EWGSOP criteria by using RASM or SMI as the muscle mass indices . The agreement of sarcopenia diagnosed by IWGS and EWGSOP criteria was only fair by using either RASM or SMI ( kappa = 0.448 by RASM , kappa = 0.471 by SMI ) . The prevalence of sarcopenia was lower by the IWGS definition than the EWGSOP definition , but it was remarkably lower by using RASM than SMI in both criteria . Overall , sarcopenic individuals defined by SMI were older , had a higher BMI but similar total skeletal muscle mass , and had poorer muscle strength and physical performance than nonsarcopenic individuals . However , by using RASM , sarcopenic individuals had less total skeletal muscle mass but similar BMI than nonsarcopenic individuals . Multivariable logistic regression showed that age was the strongest associative factor for sarcopenia in both IWGS and EWGSOP criteria . Obesity played a neutral role in sarcopenia when it is defined by using RASM , but significantly increased the risk of sarcopenia in both criteria by using SMI . CONCLUSION The agreement of sarcopenia defined by IWGS and EWGSOP was only fair , and the prevalence varied largely by using different skeletal muscle mass indices . Proper selection s for cutoff values of h and grip strength , walking speed , and skeletal muscle indices with full considerations of gender and ethnic differences were of critical importance to reach the universal diagnostic criteria for sarcopenia internationally", "The intra- and inter-tester reliability for measurement of h and grip strength and indexgrip strength using the Jamar dynamometer was investigated in 32 healthy volunteers , and the intra-tester reliability in 13 patients with cervical radiculopathy . The results from the reliability studies showed that h and grip and indexgrip strength measured with the Jamar dynamometer is a reliable method ( ICC values 0.85 - 0.98 ) and can be recommended for use in clinical practice . Age- and sex-specific reference values for h and grip strength and indexgrip strength were measured with the Jamar dynamometer in 101 r and omly selected healthy volunteers , aged 25 - 64 years . The results from the reference value study showed that sex is a more important determinant of h and strength than age , height and body weight . The reference values for h and strength improve the potential for objective evaluation of patients with arm/h and disorders caused by cervical radiculopathy", "Objectives We investigated the association between the indices of sarcopenia and future risk of cognitive impairment in older adults . Design Community-based prospect i ve cohort study . Setting Community . Participants A total of 297 participants aged ≥65 years without cognitive impairment at baseline ( mean age , 71.9 ± 6.6 years ; men : women , 158:139 ) and who underwent cognitive evaluation at the 5-year follow-up . Measurements Sarcopenia parameters including appendicular lean mass ( ALM ) , h and grip strength , and the Short Physical Performance Battery ( SPPB ) score at baseline were compared according to the later progression of mild cognitive impairment ( MCI ) and /or dementia . The operational criteria suggested by the Foundation for the National Institutes of Health Sarcopenia Project were used . We performed multivariate logistic regression analysis to identify the independent indicators of the progression of cognitive impairment . Results Among the 297 participants , 242 ( 81.5 % ) remained cognitively normal ( nonprogression group ) , whereas 55 ( 18.5 % ) showed progression of cognitive impairment ( 50 subjects ( 16.8 % ) to MCI and 5 subjects ( 1.7 % ) to dementia ) ( progression group ) . Compared with the nonprogression group , subjects in the progression group were older , had a lower educational level , and had lower physical function as assessed by the SPPB ; a higher percentage were depressed . Other baseline markers of sarcopenia , including the ALM-to-body mass index ratio and h and grip strength did not differ significantly between the groups . The association between a low SPPB score ( progression of cognitive impairment was maintained after adjustment for conventional risk factors for cognitive impairment ( hazard ratio 2.222 , 95 % confidence interval 1.047–4.716 , P = 0.038 ) . Conclusion Decreased physical performance , as assessed by the SPPB , but not other markers of sarcopenia , was independently associated with the risk of later cognitive impairment in older adults", "This study was design ed to determine the effect of testing posture and elbow position on grip strength . A h and dynamometer was used to measure the grip strength of 61 subjects ( 26 female and 35 male ) in four positions : ( 1 ) sitting with elbow in 90 degree flexion , ( 2 ) sitting with elbow in full extension , ( 3 ) st and ing with elbow in 90 degree flexion , and ( 4 ) st and ing with elbow in full extension . The four experimental conditions were r and omized , and st and ardized instructions were followed . A two-factor ( gender and treatment ) repeated measures ANOVA was used to determine any significant difference in grip strength between the sexes and the experimental ( treatment ) conditions . The result of the ANOVA revealed a significant F-ratio for gender and treatment main effects . Scheffé post hoc analysis revealed that males had higher ( p less than .01 ) grip strength than females at all the testing postures and elbow joint angles , and that there was a significant ( p less than .05 ) difference between the grip strength measured in subjects sitting with the elbow in 90 degree flexion and st and ing with the elbow in full extension . The findings suggest the need for clinicians to maintain st and ard testing conditions while measuring grip strength", "Grip strength is considered to be a good indicator of upper limb strength . The Jamar dynamometer and the Martin vigorimeter are two instruments frequently used to assess grip strength in clinical and research setting s. The purpose of this study was to compare these instruments for assessing grip strength in 360 people aged 60 to 94 years , r and omly selected from the electoral list . Anthropometric data were also collected . Data analyses were done using the maximum value on 3 trials with each instrument . Although the Martin vigorimeter is a pressure measure implying a dynamic movement as opposed to the static strength measure of the Jamar dynamometer , results indicate a very high correlation between the two measures . Grip strength measured by the Jamar dynamometer is even more dependent on h and anthropometry than measurements with the Martin vigorimeter", "Obestatin has been proposed to have anorexigenic and anti-ghrelin actions . The objective was to study obestatin concentrations in relation to h and grip strength , functional capacity and cognitive state in old women . The prospect i ve study included 110 women ( age , 76.93 ± 6.32 ) from the Mataró Ageing Study . Individuals were characterized by anthropometric variables , grip strength , Barthel and assessment of cognitive impairment [ Mini Cognoscitive Examination ( MCE ) Spanish version ] , depressive status by the Geriatric Depression Scale ( GDS ) and frailty by the Fried criteria . Obestatin was measured by IRMA . Obestatin showed negative correlation to h and grip at basal time point ( r = −0.220 , p = 0.023 ) and at 2-year follow-up ( r = −0.344 , p = 0.002 ) . Obestatin , divided into quartiles , showed a negative lineal association with h and grip : 11.03 ± 4.88 kg in first , 8.75 ± 4.08 kg in second , 8.11 ± 3.66 kg in third and 7.61 ± 4.08 kg in fourth quartile ( p = 0.018 ) . Higher obestatin levels were associated to increased weakness ( categorized by h and grip of frailty criteria ): 2.24 ± 0.42 ng/ml in weak vs. 1.87 ± 0.57 ng/ml in non-weak ( p = 0.01 ) . The decrease of either MCE or Barthel scores at 2-year follow-up was significantly higher in individuals in the fourth quartile of obestatin in comparison with individuals in the first quartile ( p = 0.046 and p = 0.019 , respectively ) . No association was found between obestatin and GDS score and neither with frailty as a condition . Obestatin is associated to low muscle strength , and impaired functional and cognitive capacity in old women participating in the Mataró Ageing Study", "OBJECTIVES To examine the association between muscle strength and total and cause-specific mortality and the plausible contributing factors to this association , such as presence of diseases commonly underlying mortality , inflammation , nutritional deficiency , physical inactivity , smoking , and depression . DESIGN Prospect i ve population -based cohort study with mortality surveillance over 5 years . SETTING Elderly women residing in the eastern half of Baltimore , Maryl and , and part of Baltimore County . PARTICIPANTS Nine hundred nineteen moderately to severely disabled women aged 65 to 101 who participated in h and grip strength testing at baseline as part of the Women 's Health and Aging Study . MEASUREMENTS Cardiovascular disease ( CVD ) , cancer , respiratory disease , other measures ( not CVD , respiratory , or cancer ) , total mortality , h and grip strength , and interleukin-6 . RESULTS Over the 5-year follow-up , 336 deaths occurred : 149 due to CVD , 59 due to cancer , 38 due to respiratory disease , and 90 due to other diseases . The unadjusted relative risk ( RR ) of CVD mortality was 3.21 ( 95 % confidence interval ( CI ) = 2.00 - 5.14 ) in the lowest and 1.88 ( 95 % CI = 1.11 - 3.21 ) in the middle compared with the highest tertile of h and grip strength . The unadjusted RR of respiratory mortality was 2.38 ( 95 % CI = 1.09 - 5.20 ) and other mortality 2.59 ( 95 % CI = 1.59 - 4.20 ) in the lowest versus the highest grip-strength tertile . Cancer mortality was not associated with grip strength . After adjusting for age , race , body height , and weight , the RR of CVD mortality decreased to 2.17 ( 95 % CI = 1.26 - 3.73 ) in the lowest and 1.56 ( 95 % CI = 0.89 - 2.71 ) in the middle , with the highest grip-strength tertile as the reference . Further adjustments for multiple diseases , physical inactivity , smoking , interleukin-6 , C-reactive protein , serum albumin , unintentional weight loss , and depressive symptoms did not material ly change the risk estimates . Similar results were observed for all-cause mortality . CONCLUSION In older disabled women , h and grip strength was a powerful predictor of cause-specific and total mortality . Presence of chronic diseases commonly underlying death or the mechanisms behind decline in muscle strength in chronic disease , such as inflammation , poor nutritional status , disuse , and depression , all of which are independent predictors of mortality , did not explain the association . H and grip strength , an indicator of overall muscle strength , may predict mortality through mechanisms other than those leading from disease to muscle impairment . Grip strength tests may help identify patients at increased risk of deterioration of health", "Background The North West Adelaide Health Study is a representative longitudinal cohort study of people originally aged 18 years and over . The aim of this study was to describe normative data for h and grip strength in a community-based Australian population . Secondary aims were to investigate the relationship between body mass index ( BMI ) and h and grip strength , and to compare Australian data with international h and grip strength norms . Methods The sample was r and omly selected and recruited by telephone interview . Overall , 3 206 ( 81 % of those recruited ) participants returned to the clinic during the second stage ( 2004 - 2006 ) which specifically focused on the collection of information relating to musculoskeletal conditions . Results Following the exclusion of 435 participants who had h and pain and /or arthritis , 1366 men and 1312 women participants provided h and grip strength measurement . The study population was relatively young , with 41.5 % under 40 years ; and their mean BMI was 28.1 kg/m2 ( SD 5.5 ) . Higher h and grip strength was weakly related to higher BMI in adults under the age of 30 and over the age of 70 , but inversely related to higher BMI between these ages . Australian norms from this sample had amongst the lowest of the h and grip strength of the internationally published norms , except those from underweight population s. Conclusions This population demonstrated higher BMI and lower grip strength in younger participants than much of the international published , population data . A complete exploration of the relationship between BMI and h and grip strength was not fully explored as there were very few participants with BMI in the underweight range . The age and gender grip strength values are lower in younger adults than those reported in international literature", "BACKGROUND It has been suggested that the age-related decline of and rogens in men plays a distinct role in the development of several aspects of frailty . Therefore , hormone replacement might improve the course of frailty by increasing lean body mass and muscle strength , decreasing fat mass , and improving the subjective quality of life . OBJECTIVE The objective of the study was to assess whether hormone replacement with dehydroepi and rosterone ( DHEA ) and /or atamestane might improve the course of frailty . DESIGN This was a double-blind , r and omized , controlled trial . SETTING The study was conducted in the general community . PARTICIPANTS Participants included 100 nonhospitalized , nondiseased , independently living men , aged 70 yr and over with low scores on strength tests . Seventeen participants did not complete the trial . INTERVENTION Subjects were r and omly assigned to one of four intervention arms : atamestane ( 100 mg/d ) and placebo , DHEA ( 50 mg/d ) and placebo , a combination of atamestane ( 100 mg/d ) and DHEA ( 50 mg/d ) , or two placebo tablets for 36 wk . MAIN OUTCOME MEASURES Physical frailty was measured by means of a specific test battery , including isometric grip strength , leg extensor power , and physical performance . RESULTS The r and omization was successful , and 83 ( 83 % ) men completed the intervention . There were no differences between the treatment arms and placebo group in any of the outcome measurements after intervention . CONCLUSIONS The results of this double-blind , r and omized trial do not support the hypothesis that hormone replacement with DHEA and /or atamestane might improve the course of frailty", "In the first part of this study , the position assumed by a normal wrist during unconstrained maximal grip and the relationship between wrist position and grip strength were investigated in 20 healthy subjects . Grip strength and wrist position were recorded in the self-selected position and then again while the subjects voluntarily deviated the wrist r and omly into flexion , extension , or radial or ulnar deviation of 10 to 15 degrees . The self-selected position was 35 degrees of extension and 7 degrees of ulnar deviation . Grip strength was significantly less in any position of deviation from this self-selected position , even after accounting for fatigue . With the wrist in only 15 degrees of extension or in neutral radio-ulnar deviation , grip strength was reduced to two thirds to three fourths of normal . Sex did not affect wrist position . The dominant wrists were within 5 degrees of the nondominant ones but were relatively less extended and in more ulnar deviation . Grip strength is significantly reduced when wrist position deviates from this self-selected optimum position . In the second part of the study , the effect of grasp size on this self-selected position was studied in 21 subjects . The degree of wrist extension was inversely and linearly related to how large a setting on the Jamar dynamometer was used . This was true regardless of h and size , although the effect was more significant for smaller h and s. Radial and ulnar deviations were not affected by h and le position . A minimum of 25 degrees of wrist extension was required for optimum grip strength . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVES The purpose of this study was to examine whether a 12-week combined physical exercise training and nutritional intervention improves physical performance and enhances health-related quality of life ( HRQOL ) among prefrail elderly women living in the community . DESIGN This was a r and omized controlled trial in which participants were recruited and r and omly assigned to the exercise and nutrition group ( EN , n = 30 ) , exercise only group ( E , n = 28 ) , and control group ( C , n = 31 ) . SETTING Group training classes were held at a research center in Itabashi Ward , Tokyo , Japan . PARTICIPANTS Eighty-nine prefrail women aged 70 years or older . INTERVENTION The EN group participated in an exercise training and nutritional program ( cooking class ) once a week , and the E group participated in the exercise training program only . MEASUREMENTS Outcome measures that included physical performance ( h and grip strength , balance , walking speed ) and HRQOL ( Medical Outcomes Study 36-Item Short Form Health Survey ) were obtained at entry , the end of the 12-week intervention , and 6 months after completion of the intervention program . RESULTS At the end of the 12-week intervention , significant improvements in the physical component summary score and 3 ( role physical , bodily pain , role emotional ) of the 8 domains of the Medical Outcomes Study 36-Item Short Form Health Survey were observed in the EN group . The E group exhibited a significantly increased h and grip strength at postintervention . The positive effects , however , were not maintained at 6-month follow-up , but were reduced . CONCLUSIONS The combined physical exercise training and nutritional intervention program has beneficial effects on several domains of HRQOL and h and grip strength in prefrail elderly women living in the community . However , further studies are needed to examine approaches that facilitate maintenance of the improved outcomes by combined exercise training and nutritional intervention", "Background Sarcopenia describes the age-associated loss of muscle mass , strength and function . The aim of this study was to compare the prevalence of sarcopenia in a cohort of community dwelling elderly people living in Berlin , Germany , according to the criteria proposed by current consensus statements and to study the respective impact on self-reported physical performance . Material and methods This study included 1405 participants from the Berlin aging study II ( BASE-II ) . The appendicular skeletal muscle mass index ( SMI ) was assessed with dual energy X-ray absorptiometry ( DXA ) , muscle strength was measured by h and grip strength and the timed up and go ” test ( TUG ) was performed as a functional parameter to reflect mobility . Results The prevalence of sarcopenia was 24.3 % in terms of reduced SMI only and considerably lower for sarcopenia with reduced grip strength ( 4.1 % ) and sarcopenia with limited mobility ( 2.4 % ) . Only 0.6 % of the participants fulfilled all three criteria . Of the subjects with a normal SMI , 8.6 % had reduced grip strength and 5.1 % had limited mobility , whereas 1.3 % subjects fulfilled both criteria . Participants with reduced strength or function reported severe difficulties in performing physical tasks significantly more often than participants with normal or reduced SMI alone ( p function . Reduced strength and function were found to be associated with a greater impact on physical performance than reduced muscle mass . Low SMI does not seem to be a prerequisite for low strength or limitations in mobility . ZusammenfassungHintergrundSarkopenie beschreibt den altersassoziierten Verlust von Muskelmasse , -kraft und -funktion . Ziel dieser Studie war es , die Sarkopenieprävalenz in einer Stichprobe zu Hause lebender Senioren nach verschiedenen , gegenwärtig empfohlenen Kriterien zu bestimmen und einen Zusammenhang mit subjektiver physischer Leistungsfähigkeit in Aktivitäten des täglichen Lebens zu erforschen . Material und Method eUntersucht wurden 1405 Teilnehmer der Berliner Altersstudie II ( BASE-II ) . Appendikuläre Skelettmuskelmasse und Skelettmuskelmasseindex ( SMI ) wurden mittels Doppel-Röntgen-Absorptiometrie ( DXA ) bestimmt . Die Muskelkraft wurde als Greifkraft gemessen , und die Mobilität als funktioneller Parameter mit dem Timed-up- and -go-Test ( TUG ) eingeschätzt . ErgebnisseDie Prävalenz der Sarkopenie betrug 24,3 % bezogen auf einen niedrigen SMI als alleiniges Kriterium und zeigte sich erheblich niedriger in Kombination der Kriterien niedriger SMI und reduzierte Greifkraft ( 4,1 % ) oder niedriger SMI und eingeschränkte Mobilität ( 2,4 % ) . Nur 0,6 % aller Teilnehmer erfüllten alle 3 Kriterien . Von Teilnehmern mit normalem SMI hatten 8,6 % eine reduzierte Greifkraft und 5,1 % eine eingeschränkte Mobilität . I m Vergleich zu Teilnehmern mit normaler Kraft oder Funktion gaben jene mit reduzierter Kraft oder Funktion signifikant häufiger Schwierigkeiten in der physischen Performance an ( p reduzierte Skelettmuskelmasse zeigte sich erheblich häufiger als eine reduzierte Greifkraft oder eingeschränkte Mobilität . Ein niedriger SMI scheint keine Voraussetzung zu sein für eine verringerte Muskelkraft oder -funktion , die ihrerseits einen stärkeren Zusammenhang mit der subjektiven physischen Leistungsfähigkeit von Senioren aufwiesen als eine reduzierte Muskelmasse", "BACKGROUND AND AIMS Falls efficacy has been shown to predict functional decline , but whether it is independently associated with frailty is still unclear . This study investigated the cross-sectional association between falls efficacy and the frailty phenotype in high-functioning older persons . METHODS Subjects ( n=861 ) were a sub- sample of community-dwelling persons aged 65 to 70 years enrolled in the \" Lc65 + \" cohort , who had gait assessment . Data included demographics , functional , cognitive , affective and health status , as well as measures of physical performance . Falls efficacy was measured with the Falls Efficacy Scale-International ( FES-I ) and frailty with Fried 's criteria . Participants were categorized into robust ( no frailty criterion ) and vulnerable ( 1 or more criteria ) . Low falls efficacy was defined as a FES-I score in the lowest quartile . RESULTS Overall , 23.9 % of participants were vulnerable . Compared with robust participants , they were more likely to report low falls efficacy ( 43.3 % vs 19.1 % , p poorer health and functional and mental status . They had slower gait speed ( 1.07+/-0.18 vs 1.15+/-0.15 m/s , p gait speed variability ( coefficient of variation 4.10+/-4.03 vs 3.33+/-1.45 % , p low falls efficacy remained associated with being vulnerable ( adjusted OR 1.80 , 95 % CI 1.19 - 2.74 , p=0.006 ) , independent of comorbidity , functional status , falls history and gait performance . CONCLUSION In high-functioning older persons , low falls efficacy was associated with vulnerability , even after controlling for gait performance and falls history . Whether low falls efficacy is a potential target on the pathway leading to frailty should be further examined prospect ively", "OBJECTIVES The objective of this study was to assess the effects of a hyperproteic , hypercaloric oral nutritional supplement with prebiotic fiber , vitamin D , and calcium , plus a st and ardized physical intervention , in the functional status , strength , nutritional status , and quality of life of frail institutionalized older adults . DESIGN Multicentric prospect i ve observational study under usual clinical practice conditions . SETTING Four nursing homes from Burgos ( 2 ) , Albacete , and Madrid , Spain . PARTICIPANTS Participants included 91 institutionalized older adults ( age ≥70 ) , able to walk 50 m , and meeting at least 3 of the Fried frailty phenotype criteria . INTERVENTION Daily intake of two 200-mL bottles of an oral nutritional supplement , each bottle containing 300 kcal , 20 g protein , 3 g fiber , 500 IU vitamin D , and 480 mg calcium , plus a st and ardized physical exercise training consisting of flexibility , balance , and strengthening exercises for arms and legs , 5 days per week . MEASUREMENTS Short Physical Performance Battery ( SPPB ) , Short-Form-Late-Life Function and Disability Instrument ( SF-LLFDI ) function subscale , h and grip strength , EuroQoL-5 Dimensions visual analogic scale ( EQ5DVAS ) , weight , body mass index ( BMI ) , and Short-Form Mini Nutritional Assessment ( MNA-SF ) at baseline and 6 and 12 weeks . RESULTS Forty-eight participants ( 52.7 % ) improved at least 1 point in the SPPB at week 6 , and 44 ( 48.4 % ) did so at week 12 ; 39 participants ( 42.9 % ) improved at least 2 points in the SF-LLFDI at week 6 , and 46 ( 50.5 % ) at week 12 . Participants improved their quality of life measured with the EQ5DVAS by 6 % ( 95 % confidence interval [ CI ] 3%-10 % ) at week 6 , and by 5 % ( 95 % CI 0%-10 % ) at week 12 . They also improved their nutritional status ( weight gain , BMI increase , and higher MNA-SF scores at 6- and 12-week follow-up ) . This improvement was higher in participants with more frailty criteria , lower functional level , lower vitamin D levels , and poorer nutritional status . CONCLUSION A 12-week intervention with oral nutritional supplementation plus physical exercise improves function , nutritional status , and quality of life in frail institutionalized older adults", "Grip strength is used in the assessment of h and and upper limb function . Current recommendations state that taking the mean of three repeated grip trials provides more reliable results than only one trial . A repeated measures , crossover design was used . Sixty-six subjects were recruited ( 22 asymptomatic subjects , 22 following carpal tunnel decompression , and 22 following flexor tendon repair ) . Grip strength testing was performed on a Jamar dynamometer using a st and ardized testing protocol . Pre- and post testing pain levels were recorded using a verbal analogue scale . Each subject 's grip strength was tested four times , twice using a single trial protocol and twice using three grip trials in r and om order . Intraclass correlation coefficients ( ICC ) ( 2,1 ) , 95 % confidence intervals , and st and ard error of measurements were calculated . A two-tailed paired sample s t-test was used to investigate the difference between the grip strength values obtained and the changes in verbal analogue scale . High levels of test-retest reliability ( ICC > or=0.85 ) were found for the three methods of grip strength testing ( one trial , the mean of three trials , and the best of three trials ) . The mean values of grip strength generated for each method of grip strength testing produced comparable results . A significant difference ( p > or=0.0001 ) was observed in the verbal analogue scale scores following one trial and three in all three sample groups . Clinical ly acceptable levels of reliability ( > or=0.91 ) were demonstrated by all three methods of grip strength testing other than the mean of three trials for the asymptomatic group . Distribution of the ICC results and the elevated verbal analogue scales associated with three trials suggest that the use of one grip trial may be appropriate . This study suggests that one maximal trial is as reliable as and less painful than either the best of , or , mean of three trials", "OBJECTIVES To describe the association between frailty and health status , the progression of frailty , and the relationship between frailty and mortality in older men . DESIGN Cross-sectional and prospect i ve cohort study . SETTING Six U.S. clinical centers . PARTICIPANTS Five thous and nine hundred ninety-three community-dwelling men aged 65 and older . MEASUREMENTS Frailty was defined as three or more of the following : sarcopenia ( low appendicular skeletal mass adjusted for height and body fat ) , weakness ( grip strength ) , self-reported exhaustion , low activity level , and slow walking speed . Prefrail men met one or two criteria ; robust men had none . Follow-up averaged 4.7 years . RESULTS At baseline , 240 subjects ( 4.0 % ) were frail , 2,395 ( 40.0 % ) were prefrail , and 3,358 were robust ( 56.0 % ) . Frail men were less healthy in most measures of self-reported health than prefrail or robust men . Frailty was somewhat more common in African Americans ( 6.6 % ) and Asians ( 5.8 % ) than Caucasians ( 3.8 % ) . At the second visit , men who were frail at baseline tended to remain frail ( 24.2 % ) or die ( 37.1 % ) or were unable to complete the follow-up visit ( 26.2 % ) ; robust men tended to remain robust ( 54.4 % ) . Frail men were approximately twice as likely to die as robust men ( multivariate hazard ratio (MHR)=2.05 , 95 % confidence interval (CI)=1.55 - 2.72 ) . Mortality risk for frail men was greater in all weight categories than for nonfrail men but was highest for normal-weight frail men ( MHR=2.39 , 95 % CI=1.51 - 3.79 , P for interaction=.01 ) . The relationship between frailty and mortality was somewhat stronger in younger men than older men ( P for interaction=.01 ) . CONCLUSION Frailty in older men is associated with poorer health and a greater risk of mortality", "BACKGROUND Sarcopenia , an age- related loss of muscle mass , is a significant associating factor for functional impairment among older adults . The aim of this study was to investigate the prevalence of and associated factors for sarcopenia and severe sarcopenia among older adults in Iran . METHODS A total of 300 individuals aged over 55 years were r and omly selected from the 6th district of Tehran , Iran , in 2011 . Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People ( EWGSOP ) algorithm . The skeletal muscle mass was assessed using DXA . Muscle strength and muscle performance were assessed according to h and grip strength and 4-m usual walking gait speed test . A logistic regression analysis was performed . RESULTS The prevalence values of presarcopenia , sarcopenia , and severe sarcopenia were 52.7 % , 20.7 % , and 6 % , in men and 25.3 % , 15.3 % , and 5.3 % in women , respectively . The prevalence of sarcopenia was higher in men older than 75 years than women in the same age range ( 36.7 % versus 20 % , respectively ) . Using multiple logistic regression models , age , sex , smoking , and body mass index ( BMI ) were independently associated with different stages of sarcopenia . CONCLUSIONS The prevalence of sarcopenia is high in Iranian older adults . The older age , male sex , smoking and lower BMI were independently associated with presarcopenia , sarcopenia and severe sarcopenia", "OBJECTIVES Protein supplementation has been proposed as an effective dietary strategy to augment the skeletal muscle adaptive response to prolonged resistance-type exercise training in elderly people . Our objective was to assess the impact of protein supplementation on muscle mass , strength , and physical performance during prolonged resistance-type exercise training in frail elderly men and women . DESIGN / SETTING / PARTICIPANTS A r and omized , double-blind , placebo-controlled trial with 2 arms in parallel among 62 frail elderly subjects ( 78 ± 1 year ) . These elderly subjects participated in a progressive resistance-type exercise training program ( 2 sessions per week for 24 weeks ) during which they were supplemented twice daily with either protein ( 2 * 15 g ) or a placebo . MEASUREMENTS Lean body mass ( DXA ) , strength ( 1-RM ) , and physical performance ( SPPB ) were assessed at baseline , and after 12 and 24 weeks of intervention . RESULTS Lean body mass increased from 47.2 kg ( 95 % CI , 43.5 - 50.9 ) to 48.5 kg ( 95 % CI , 44.8 - 52.1 ) in the protein group and did not change in the placebo group ( from 45.7 kg , 95 % CI , 42.1 - 49.2 to 45.4 kg , 95 % CI , 41.8 - 48.9 ) following the intervention ( P value for treatment × time interaction = .006 ) . Strength and physical performance improved significantly in both groups ( P = .000 ) with no interaction effect of dietary protein supplementation . CONCLUSIONS Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance in frail elderly people . Dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people . TRIAL REGISTRATION clinical trials.gov identifier : NCT01110369", "OBJECTIVES The aim of this study was to examine the association between physical frailty and social functioning among older adults , cross-sectionally and prospect ively over 3 years . STUDY DESIGN The study sample consisted of 1115 older adults aged 65 and over from two waves of the Longitudinal Aging Study Amsterdam , a population based study . MAIN OUTCOME MEASURES Frailty was measured at T1 ( 2005/2006 ) using the criteria of the frailty phenotype , which includes weight loss , weak grip strength , exhaustion , slow gait speed and low physical activity . Social functioning was assessed at T1 and T2 ( 2008/2009 ) and included social network size , instrumental support , emotional support , and loneliness . RESULTS Cross-sectional linear regression analyses adjusted for covariates ( age , sex , educational level and number of chronic diseases ) showed that pre-frail and frail older adults had a smaller network size and higher levels of loneliness compared to their non-frail peers . Longitudinal linear regression analyses adjusted for covariates and baseline social functioning showed that frailty was associated with an increase in loneliness over 3 years . However , the network size and levels of social support of frail older adults did not further decline over time . CONCLUSIONS Frailty is associated with poor social functioning , and with an increase in loneliness over time . The social vulnerability of physical frail older adults should be taken into account in the care provision for frail older adults", "Numerous studies have shown that elbow positioning influences grip measurements . These studies have had various and contradictory results . The intent of this study was to clarify the discrepancies and determine which elbow position yields maximal grip strength . Sixty-four men and 64 women were tested on a Greenleaf Medical EVAL system , once with the elbow in full extension and once with the elbow in 90 degrees of flexion . With larger subject groups and computerized data collection , results indicate that-for both the dominant and nondominant h and s and regardless of the gender of the subject-grip strength is significantly greater when measured with the elbow in the fully extended position", "OBJECTIVES To categorize the health problems of older Russians and identify the number of frail older adults using different approaches . DESIGN Cross-sectional study . SETTING The Kolpino district of St. Petersburg . PARTICIPANTS A r and om sample of 611 community-dwelling adults aged 65 and older was selected from a population -based register and stratified into two age groups ( 65 - 74 , ≥75 ) . MEASUREMENTS Anthropometry , medical history , nutritional status , Physical Performance Battery , activities of daily living , grip strength , spirometry , renal function , 15-item Geriatric Depression Scale , Mini-Mental State Examination , and sense of coherence . RESULTS The female : male ratio was 2.5:1 ; 19 % were malnourished or at risk for malnutrition , and 78.6 % presented with one to three chronic pathologies , with no differences according to age or sex . Problems with hearing ( 60.7 % ) , vision ( 89.5 % ) , and incontinence ( 40.9 % ) were highly prevalent . Moreover , 25.9 % of the younger group ( 65 - 74 ) and 42.5 % of the older group ( ≥75 ) were found to be at risk for depression . Mild to severe cognitive impairment was found in 34.5 % of the participants , and 14.4 % of those aged 65 to 74 and 33.0 % of those aged 75 and older reported dependence in daily living activities . The prevalence of frailty assessed using different models varied from 21.1 % to 43.9 % . The Fried model revealed the strongest associations with the frailty outcomes ( dependence and performance ) . No significant differences between the sexes were found in either age group ( P=.82 ) , although the percentage of frail women increased with age ( P=.001 ) . CONCLUSION The findings emphasize the need for attention and re sources to be shifted from disease-oriented to functional approaches in the older Russian population . The population studied is consistent with the Fried model , in which one in five older adults can be labeled as frail", "OBJECTIVE The European Working Group of Sarcopenia in Older People ( EWGSOP ) has developed an algorithm based on gait speed measurement to begin sarcopenia case-finding in clinical practice , in which a cut-off point of community-dwelling older people . The objective of this study was to assess the application of the EWGSOP algorithm in hospitalised elderly patients with impaired functional capacity . METHODS One hundred in- patients ( aged 84.1 SD 8.5 , 62 % women ) were prospect ively studied in a postacute care geriatric unit focused on rehabilitation . Sarcopenia was assessed by corporal composition ( electrical bioimpedance ) , h and grip strength , and physical performance ( gait speed ) . Other measurements were Charlson index , length of stay , and functional gain at discharge and 3-month follow-up . All patients were screened by the EWGSOP algorithm and sarcopenia was confirmed according to diagnostic criteria . RESULTS Gait speed was low muscle mass , which , according to the EWGSOP-algorithm , would indicate a diagnosis of sarcopenia . No differences were observed in functional capacity between these patients and those with normal muscle mass . When decreased h and grip strength was considered , 47 of these patients met the EWGSOP criteria for severe sarcopenia . In this group , differences in functional capacity were observed at discharge ( Barthel 45.2 vs. 56.3 , p=0.042 ) and 3-month follow-up ( 48.3 vs. 59.8 , p=0.047 ) . CONCLUSION The application of the EWGSOP algorithm in hospitalised , postacute , elderly patients with low gait speed suggested that muscle strength should be considered before confirming or discarding a sarcopenia diagnosis" ]	41184032-06ff-11f0-808a-c43d1ab1c353
BACKGROUND The minimal clinical ly important difference ( MCID ) is used when interpreting the importance of outcome data . However , a consensus regarding the MCID for commonly used patient-reported outcomes in shoulder surgery has not been established . The purpose of this systematic review was to evaluate the available literature on shoulder MCID to improve clinical interpretation of shoulder outcome data . METHODS A systematic review of the literature was conducted to identify studies reporting anchor-based MCID values for the patient-reported outcomes recommended by the American Shoulder and Elbow Surgeons ( ASES ) : Veterans R and 12 score , ASES score , Single Assessment Numeric Evaluation ( SANE ) score , Western Ontario Rotator Cuff ( WORC ) score , Western Ontario Osteoarthritis Score ( WOOS ) , Western Ontario Shoulder Instability Index ( WOSI ) , Pennsylvania Shoulder Score , and Oxford Shoulder Score ( OSS ) . RESULTS A total of 14 articles reporting anchor-based MCID values were included in the final analysis . No studies reporting the Western Ontario Osteoarthritis Score ( WOOS ) were identified . The ASES score ( 6 studies ) , OSS ( 4 studies ) , and WORC score ( 2 studies ) were the only instruments investigated in more than 1 study . The average reported MCID values for the ASES , OSS , and WORC scores were 15.5 ( 15 % total difference ) , 275.7 ( 13 % total difference ) , and 6 ( 13 % total difference ) , respectively . The vast majority of studies failed to report information necessary to vali date the credibility of these MCID values . DISCUSSION AND CONCLUSION The current utility of the MCID for patient-report shoulder outcome instruments is limited by poor study methodology , inadequate reporting , and a lack of data . Further research is needed to more clearly define the MCID values for commonly used patient-reported outcomes in shoulder surgery	[ "Study Design A prospect i ve cohort study nested in a r and omized controlled trial . Objectives To determine and compare responsiveness and minimal clinical ly important change of the modified Constant score ( CS ) and the Oxford Shoulder Score ( OSS ) . Background The OSS and the CS are commonly used to assess shoulder outcomes . However , few studies have evaluated the measurement properties of the OSS and CS in terms of responsiveness and minimal clinical ly important change . Methods The study included 126 patients who reported having difficulty returning to usual activities 8 to 12 weeks after arthroscopic decompression surgery for subacromial impingement syndrome . The assessment at baseline and at 3 months included the OSS , the CS , and the European Quality of Life-5 Dimensions-3 Level ( EQ-5D-3L ) index . Responsiveness was assessed as follows : by correlation analysis between the change scores of the OSS , CS , and EQ-5D-3L index , and the Patient Global Impression of Change ( PGIC ) scale ; by receiver-operating-characteristic ( ROC ) curve analysis using the PGIC scale as an external anchor ; and by effect-size statistics . Results At 3 months , a follow-up assessment of 112 patients ( 89 % ) was conducted . The change scores of the CS and the OSS were more strongly correlated with the external anchor ( PGIC scale ) than the change score of the EQ-5D-3L index . The areas under the ROC curves exceeded 0.80 for both shoulder scores , with no significant differences between them , and comparable effect-size estimates were observed for the CS and the OSS . Minimal clinical ly important change ROC values were 6 points for the OSS and 11 points for the CS , with upper 95 % cutoff limits of 12 and 22 points , respectively . Conclusion The CS and the OSS were both suitable for assessing improvement after decompression surgery", "BACKGROUND Knowledge about Minimal Important Differences ( MIDs ) is essential for the interpretation of continuous outcomes , especially patient-reported outcome measures ( PROMS ) . OBJECTIVE The aim of this study was to estimate the MID for the Western Ontario Rotator Cuff Index ( WORC : score 0 ( best ) to 2100 ( worst disability ) ) in adults with shoulder pain associated with partial-thickness rotator cuff tears , ' symptomatic PTTs ' , undergoing conservative treatment with physiotherapy . DESIGN A prospect ively- design ed anchor-based MID analysis using data from a prospect i ve prognostic study with a three-month follow-up conducted within an outpatient care setting in Germany . METHODS The MID was estimated using data from 64 adults with atraumatic symptomatic PTTs who underwent three months of conservative treatment with physiotherapy . The anchor was a seven-point Global Perceived Change ( GPC ) scale . RESULTS Based on a definition of the MID being the threshold of \" being ( at least slightly ) improved \" with a probability nearest to 0.90 ( i.e. 9 of 10 patients achieving the MID ) , the MID for the WORC was estimated as -300 for ' improved ' shoulder-related disability in 9 out of 10 patients ( 95 % CI 8 out of 10 patients to everyone ) undergoing three months of exercise-based physiotherapy for symptomatic PTTs . CONCLUSIONS This is the first published MID estimate for the WORC in adults with symptomatic PTTs of the rotator cuff undergoing typical treatment comprising conservative treatment with physiotherapy . The conceptual framework for interpretation facilitates its use in similar clinical context", "In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials", "We developed a 12-item question naire for completion by patients having shoulder operations other than stabilisation . A prospect i ve study of 111 patients was undertaken before operation and at follow-up six months later . Each patient completed the new question naire and the SF36 form . Some filled in the Stanford Health Assessment Question naire ( HAQ ) . An orthopaedic surgeon assessed the Constant shoulder score . The single score derived from the question naire had a high internal consistency . Reproducibility , examined by test-retest reliability , was found to be satisfactory . The validity of the question naire was established by obtaining significant correlations in the expected direction with the Constant score and the relevant scales of the SF36 and the HAQ . Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up . Changes in scores were compared with the patients ' responses to postoperative questions about their condition . The st and ardised effect size for the new question naire compared favourably with that for the SF36 and the HAQ . The new question naire was the most efficient in distinguishing patients who said that their shoulder was much better from all other patients . The shoulder question naire provides a measure of outcome for shoulder operations which is short , practical , reliable , valid and sensitive to clinical ly important changes", "The purpose of this study was to examine the psychometric properties of the American Shoulder and Elbow Surgeons St and ardized Shoulder Assessment Form ( ASES ) , patient self-report section . Patients with shoulder dysfunction ( n = 63 ) completed the ASES , The University of Pennsylvania Shoulder Score , and the Short Form-36 during the initial evaluation , 24 to 72 hours after the initial visit , and after 3 to 4 weeks of physical therapy . The test-retest reliability ( intraclass correlation coefficient[1-way r and om-effects ] , 0.84 ; 95 % CI lower limit , 0.75 ) and internal consistency ( Cronbach alpha , 0.86 ) values were acceptable . The st and ard error of the measure was 6.7 ASES points ( 90 % CI , 11.0 ) . Construct and discriminant validity was demonstrated . Responsiveness was demonstrated with a st and ardized response mean of 1.5 and an effect size of 1.4 . The minimal detectable change was 9.7 ASES points ( 90 % CI , 16 ) , and the minimal clinical ly important difference was 6.4 ASES points . The results indicate that the ASES is a reliable , valid , and responsive outcome tool", "OBJECTIVES Estimates of minimal clinical ly important differences in health measures may be affected by the anchor used . We examined if domain-specific transition questions had higher construct validity than global health transition questions as anchors for measures in a given domain . STUDY DESIGN AND SETTING In a prospect i ve study of 249 patients with rheumatoid arthritis , we examined changes in pain , physical function , joint swelling , stiffness , fatigue , and depression with treatment . We related these changes to a domain-specific transition question , global arthritis transition question , and the Short Form-36 ( SF-36 ) health transition item . RESULTS Changes in all six clinical measures were more highly correlated with the domain-specific transition questions than with the global arthritis question and SF-36 transition question . Discrimination between patients who improved or not was also better using domain-specific questions . Estimates of minimal clinical ly important improvement ( MCII ) differed with the anchor when these were based on mean changes . MCII estimates from receiver operating characteristic curve analysis were not influenced by the choice of anchor when anchors had high agreement . CONCLUSION Domain-specific transition questions had higher construct validity as anchors for determining clinical ly important differences in health measures focused on a single domain than either global disease or general health transition questions", "OBJECTIVE To determine distribution- and anchor-based minimal important difference ( MID ) estimates for four scores from the Functional Assessment of Cancer Therapy-Breast ( FACT-B ) : the breast cancer subscale ( BCS ) , Trial Outcome Index ( TOI ) , FACT-G ( the general version ) , and FACT-B. STUDY DESIGN AND SETTING We used data from a Phase III clinical trial in metastatic breast cancer ( ECOG study 1193 ; n=739 ) and a prospect i ve observational study of pain in metastatic breast cancer ( n=129 ) . One third and one half of the st and ard deviation and 1 st and ard error of measurement were used as distribution-based criteria . Clinical indicators used to determine anchor-based differences included ECOG performance status , current pain , and response to treatment . RESULTS FACT-B scores were responsive to performance status and pain anchors , but not to treatment response . By combining the results of distribution- and anchor-based methods , MID estimates were obtained : BCS=2 - 3 points , TOI=5 - 6 points , FACT-G=5 - 6 points , and FACT-B=7 - 8 points . CONCLUSION Distribution- and anchor-based estimates of the MID do show convergence . These estimates can be used in combination with other measures of efficacy to determine meaningful benefit and provide a basis for sample size estimation in clinical trials", "The aim of this study is to show the relationship between test-retest reproducibility and responsiveness and to introduce the smallest real difference ( SRD ) approach , using the sickness impact profile ( SIP ) in chronic stroke patients as an example . Forty chronic stroke patients were interviewed twice by the same examiner , with a 1-week interval . All patients were interviewed during the qualification period preceding a r and omized clinical trial . Test-retest reproducibility has been quantified by the intraclass correlation coefficient ( ICC ) , the st and ard error of measurement ( SEM ) and the related smallest real difference ( SRD ) . Responsiveness was defined as the ratio of the clinical ly relevant change to the SD of the within-stable-subject test-retest differences . The ICC for the total SIP was 0.92 , whereas the ICCs for the specified SIP categories varied from 0.63 for the category ‘ recreation and pastime ’ to 0.88 for the category ‘ work ’ . However , both the SEM and the SRD far more capture the essence of the reproducibility of a measurement instrument . For instance , a total SIP score of an individual patient of 28.3 % ( which is taken as an example , being the mean score in the study population ) should decrease by at least 9.26 % or approximately 13 items , before any improvement beyond reproducibility noise can be detected . The responsiveness to change of a health status measurement instrument is closely related to its test-retest reproducibility . This relationship becomes more evident when the SEM and the SRD are used to quantify reproducibility , than when ICC or other correlation coefficients are used", "OBJECTIVE To compare the st and ard error of measurement ( SEM ) with established st and ards for clinical ly relevant intra-individual change in an evaluation of health-related quality of life . DESIGN Secondary analysis of data from a r and omized controlled trial . SUBJECTS Six hundred and five out patients with a history of cardiac problems attending the general medicine clinics of a major academic medical center . MEASURES Baseline and follow-up interviews included a modified version of the Chronic Heart Failure Question naire ( CHQ ) and the SF-36 . The SEM values corresponding to established st and ards for minimal clinical ly important differences ( MCIDs ) on the CHQ were determined . Individual change on the SF-36 was explored using the same SEM criterion . RESULTS One-SEM changes in this population corresponded well to the patient-driven MCID st and ards on all CHQ dimensions ( weighted kappas ( 0.87 ; P SEM to evaluate individual patient change should be explored among other health-related quality of life instruments with established st and ards for clinical ly relevant differences . Only then can it be determined whether the one-SEM criterion can be consistently applied as a proxy for clinical ly meaningful change", "Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases", "OBJECTIVE To estimate minimally important differences ( MIDs ) on the Functional Assessment of Cancer Therapy-Colorectal ( FACT-C ) instrument using anchor- and distribution-based methods . STUDY DESIGN AND SETTING Preliminary MIDs were generated for FACT-C scores based on published results for two sample s ( n = 60 and n = 63 ) from the FACT-C validation study . Preliminary MIDs were confirmed using data from a Phase II r and omized controlled clinical trial ( n = 104 ) and a population -based observational study ( n = 568 ) . MIDs were estimated for the colorectal cancer subscale ( CCS ) ; the FACT-C Trial Outcome Index ( TOI-C ) , which is the sum of the CCS , physical well-being , and functional well-being subscales ; and the FACT-C total score . Both cross-sectional and longitudinal analyses were used . RESULTS MIDs were stable across the different patient sample s. The recommended MIDs ranged from 2 to 3 points for the CCS , 4 to 6 points for the TOI-C , and 5 to 8 points for the FACT-C total score . CONCLUSIONS MIDs can enhance the interpretability of FACT-C scores , and they can be used to provide a basis for sample size estimation and to determine clinical benefit in combination with other measures of efficacy . General guidelines for estimating MIDs for other FACT instruments are suggested", "BACKGROUND In clinical trials , at the group level , results are usually reported as mean and st and ard deviation of the change in score , which is not meaningful for most readers . OBJECTIVE To determine the minimal clinical ly important improvement ( MCII ) of pain , patient 's global assessment of disease activity , and functional impairment in patients with knee and hip osteoarthritis ( OA ) . METHODS A prospect i ve multicentre 4 week cohort study involving 1362 out patients with knee or hip OA was carried out . Data on assessment of pain and patient 's global assessment , measured on visual analogue scales , and functional impairment , measured on the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) function subscale , were collected at baseline and final visits . Patients assessed their response to treatment on a five point Likert scale at the final visit . An anchoring method based on the patient 's opinion was used . The MCII was estimated in a subgroup of 814 patients ( 603 with knee OA , 211 with hip OA ) . RESULTS For knee and hip OA , MCII for absolute ( and relative ) changes were , respectively , ( a ) -19.9 mm ( -40.8 % ) and -15.3 mm ( -32.0 % ) for pain ; ( b ) -18.3 mm ( -39.0 % ) and -15.2 mm ( -32.6 % ) for patient 's global assessment ; ( c ) -9.1 ( -26.0 % ) and -7.9 ( -21.1 % ) for WOMAC function subscale score . The MCII is affected by the initial degree of severity of the symptoms but not by age , disease duration , or sex . CONCLUSION Using criteria such as MCII in clinical trials would provide meaningful information which would help in interpreting the results by expressing them as a proportion of improved patients", "OBJECTIVE To discuss the concepts of the minimal clinical ly important difference ( MCID ) and the smallest detectable difference ( SDD ) and to examine their relation to required sample sizes for future studies using concrete data of the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and the generic Medical Outcomes Study 36-Item Short Form ( SF-36 ) in patients with osteoarthritis of the lower extremities undergoing a comprehensive inpatient rehabilitation intervention . METHODS SDD and MCID were determined in a prospect i ve study of 122 patients before a comprehensive inpatient rehabilitation intervention and at the 3-month followup . MCID was assessed by the transition method . Required SDD and sample sizes were determined by applying normal approximation and taking into account the calculation of power . RESULTS In the WOMAC sections the SDD and MCID ranged from 0.51 to 1.33 points ( scale 0 to 10 ) , and in the SF-36 sections the SDD and MCID ranged from 2.0 to 7.8 points ( scale 0 to 100 ) . Both question naires showed 2 moderately responsive sections that led to required sample sizes of 40 to 325 per treatment arm for a clinical study with unpaired data or total for paired followup data . CONCLUSION In rehabilitation intervention , effects larger than 12 % of baseline score ( 6 % of maximal score ) can be attained and detected as MCID by the transition method in both the WOMAC and the SF-36 . Effects of this size lead to reasonable sample sizes for future studies lying below n = 300 . The same holds true for moderately responsive question naire sections with effect sizes higher than 0.25 . When design ing studies , assumed effects below the MCID may be detectable but are clinical ly meaningless", "OBJECTIVE The purpose of this study was to determine the minimal important change ( MIC ) of improvement in the Constant-Murley score in patients with long-st and ing subacromial pain and in subgroups of patients with subacromial pain with and without rotator cuff ruptures . METHOD The MIC was estimated by the anchor-based MIC distribution method , which integrates an anchor- and distribution-based approach : the optimal cutoff point of the receiver operating characteristic curve ( MICROC ) and the 95 % limit cutoff point ( MIC95 % limit ) . The study population consisted of 93 patients included in a r and omized clinical trial evaluating the effect of a specific exercise strategy . RESULTS The MICROC was found at a mean change of 17 points in the Constant-Murley score , which corresponds to a sensitivity of 91 % and a specificity of 79 % . The MIC95 % limit was found at a mean change of 24 points . In the subgroup analysis , the MICROC was found at a mean change of 19 points and the MIC95 % limit at 18 points in patients with an intact rotator cuff . In patients with rotator cuff ruptures , the MICROC was found at a mean change of 15 points and the MIC95 % limit at 30 points . CONCLUSION The Constant-Murley score is able to detect the MIC in individual patients with long-st and ing subacromial pain when the rotator cuff is intact . The estimated MIC values could be used as an indication for relevant changes in the Constant-Murley score in clinical practice and guide the clinician in how to interpret the results of specific treatments" ]	411840b4-06ff-11f0-808a-c43d1ab1c353
BACKGROUND A recent review concluded that general health checks fail to reduce mortality in adults . AIM This review focuses on general practice -based health checks and their effects on both surrogate and final outcomes . DESIGN AND SETTING Systematic search of PubMed , Embase , and the Cochrane Central Register of Controlled Trials . METHOD Relevant data were extracted from r and omised trials comparing the health outcomes of general practice -based health checks versus usual care in middle-aged population s. RESULTS Six trials were included . The end-point differences between the intervention and control arms in total cholesterol ( TC ) , systolic and diastolic blood pressure ( SBP , DBP ) , and body mass index ( BMI ) were -0.13 mmol/l ( 95 % confidence interval [ CI ] = -0.19 to -0.07 ) , -3.65 mmHg ( 95 % CI = -6.50 to -0.81 ) , -1.79 mmHg ( 95 % CI = -2.93 to -0.64 ) , and -0.45 kg/m(2 ) ( 95 % CI = -0.66 to -0.24 ) , respectively . The odds of a patient remaining at ' high risk ' with elevated TC , SBP , DBP , BMI or continuing smoking were 0.63 ( 95 % CI = 0.50 to 0.79 ) , 0.59 ( 95 % CI = 0.28 to 1.23 ) , 0.63 ( 95 % CI = 0.53 to 0.74 ) , 0.89 ( 95 % CI = 0.81 to 0.98 ) , and 0.91 ( 95 % CI = 0.82 to 1.02 ) , respectively . There was little evidence of a difference in total mortality ( OR 1.03 , 95 % CI = 0.90 to 1.18 ) . Higher CVD mortality was observed in the intervention group ( OR 1.30 , 95 % CI = 1.02 to 1.66 ) . CONCLUSION General practice -based health checks are associated with statistically significant , albeit clinical ly small , improvements in surrogate outcome control , especially among high-risk patients . Most studies were not originally design ed to assess mortality	[ "Background Treatment goals for cardiovascular risk management are generally not achieved . Specialized practice nurses are increasingly facilitating the work of general practitioners and self-monitoring devices have been developed as counseling aid . The aim of this study was to compare st and ard treatment supported by self-monitoring with st and ard treatment without self-monitoring , both conducted by practice nurses , on cardiovascular risk and separate risk factors . Methods Men aged 50–75 years and women aged 55–75 years without a history of cardiovascular disease or diabetes , but with a SCORE 10-year risk of cardiovascular mortality ≥5 % and at least one treatable risk factor ( smoking , hypertension , lack of physical activity or overweight ) , were r and omized into two groups . The control group received st and ard treatment according to guidelines , the intervention group additionally received pro-active counseling and self-monitoring ( pedometer , weighing scale and / or blood pressure device ) . After one year treatment effect on 179 participants was analyzed . Results SCORE risk assessment decreased 1.6 % ( 95 % CI 1.0–2.2 ) for the control group and 1.8 % ( 1.2–2.4 ) for the intervention group , difference between groups was .2 % ( −.6–1.1 ) . Most risk factors tended to improve in both groups . The number of visits was higher and visits took more time in the intervention group ( 4.9 ( SD2.2 ) vs. 2.6 ( SD1.5 ) visits p groups cardiovascular risk decreased significantly after one year of treatment by practice nurses . No additional effect of basing the pro-active counseling on self-monitoring was found , despite the extra time investment . Trial registration trialregister.nl", "Abstract The drop-out problem was studied in a r and omly selected population sample of men invited to a primary preventive trial against coronary heart disease among middle-aged men . Participants and non- participants in the intervention group were compared with regard to mortality , causes of death , autopsy findings , morbidity and sobriety . The non-participation group was characterized by a somewhat higher prevalence of chronic diseases and alcoholic problems . These features were more pronounced in subjects who died during the follow-up compared to still living subjects . Mortality , total as well as cause-specific , was considerably higher among non- participants . The death rate was higher in the non-participation group irrespective of duration of sick leave . The amount of coronary atherosclerosis , evaluated post-mortem , was essentially the same in those who died in the participation and non-participation groups . The difference in characteristics between participants and non- participants affects the possibilities of generalization to the total population under study . Similar differences between participants and non- participants are certainly present in other studies too", "AIM The aim of this paper is to describe the prevalence of cardiovascular risk factors in families screened systematic ally by nurses in British general practice , and in subgroups with reported hypertension , hypercholesterolaemia , diabetes and coronary heart disease . METHOD Twenty six general practice s ( 13 intervention and 13 control practice s ) in 13 towns in Engl and , Wales and Scotl and were involved in a r and omized control trial . R and omly ordered invitations were sent for a family health check to 4158 households ( men aged 40 - 59 years and their partners ) registered with the 13 intervention practice s. RESULTS One or more adult members from 2373 households ( 57 % ) were screened ; in 1477 visits the selected man and his female partner attended of whom 98 % were married . In all , 3850 individuals were screened ( 2246 men and 1604 women ) ; 15 % of men and women were in the predefined top quintile of the British family heart study risk score . Twenty four per cent of men and 22 % of women smoked cigarettes and 62 % of men and 44 % of women were overweight ( body mass index 25 + ) . One third of men and one sixth of women with no known history of high blood pressure had a diastolic blood pressure of 90 + mmHg . Among the 491 individuals with previously reported high blood pressure 64 % were not adequately controlled , having a diastolic blood pressure of 90 + mmHg , while 26 % had diastolic blood pressure of 100 + mmHg . Eighteen per cent of men and women with no known history of a high cholesterol level had a r and om cholesterol level of 6.5 + mmol l-1 . In the 173 people with a previously reported high cholesterol level and who had their level measured over half had a cholesterol level of 6.5 + mmol l-1 and in 7 % this level was 8.0 + mmol l-1 . One per cent of men and 0.3 % of women were newly identified as diabetic ( r and om glucose level of 10.0 + mmol l-1 ) . In the 52 with previously diagnosed diabetes unsatisfactory control was found in 52 % ( r and om level of 10.0 + mmol l-1 ) . A total of 3034 men and women overall ( 79 % ) qualified for follow up for one or more risk factor ; 1909 men ( 85 % ) and 1125 women ( 70 % ) . Among the 139 with pre-existing coronary heart disease 119 ( 86 % ) had modifiable risk factors : 27 % were cigarette smokers , 68 % had a body mass index of 25 + , 40 % had diastolic hypertension , 29 % had hypercholesterolaemia and 19 % had hyperglycaemia . Five per cent of men and women were taking antihypertensive drugs , 0.3 % cholesterol lowering drugs and 0.7 % drugs for diabetes . CONCLUSION There is considerable scope for primary and secondary prevention among families registered with general practice s , but whether nursing and medical intervention can reduce the risk factors related to cardiovascular disease in this setting remains unknown", "OBJECTIVES To investigate the impact of general health screenings and discussion s with general practitioners on the cardiovascular risk profile of a r and om population of patients . STUDY DESIGN A population -based , r and omized , controlled , 5-year follow-up trial conducted in a primary care setting . POPULATION The study group consisted of 2000 patients , r and omly selected middle-aged men and women aged 30 to 50 years from family practice s in the district of Ebeltoft , Denmark . Of these patients , 1507 ( 75.4 % ) agreed to participate . Patients were r and omized into ( 1 ) a control group who did not receive health screenings , ( 2 ) an intervention group that received 2 health screenings , ( 3 ) an intervention group that received both the 2 screenings and a 45-minute follow-up consultation annually with their general practitioner . OUTCOMES MEASURED Cardiovascular risk score ( CRS ) , body mass index ( BMI ) , blood pressure , serum cholesterol , carbon monoxide in expiratory air , and tobacco use . RESULTS After 5 years , the CRS , BMI , and serum cholesterol levels were lower in the intervention groups compared with the control group . The improved outcome was greater in the baseline risk groups . The number of patients with elevated CRS in the intervention groups was approximately half the number of patients with elevated CRS in the control group . The difference was not a result of medication use . There was no difference between the group that received consultations after the screenings and the group that had health screenings alone . CONCLUSIONS Health screenings reduced the CRS in the intervention groups . After 5 years of follow-up , the number of persons at elevated cardiovascular risk was about half that expected , based on the prevalence/proportion in a population not receiving the health checks ( the control group ) . The impact of intervention was higher among at-risk individuals . Consultations about health did not appear to improve the cardiovascular profile of the study population", "The objectives of this study were to : ( 1 ) study if an opportunistic screening of coronary heart disease ( CHD ) risk factors among male attenders in general practice ( GP ) influenced the overall subjective satisfaction with life of persons labelled ‘ high risk ’ compared to other screened persons ; ( 2 ) compare psychological well-being and patient satisfaction in a patient centred and self-directive ( PCSD ) intervention with conventional care ( CC ) ; and ( 3 ) evaluate patient satisfaction and psychological well-being among subjects with high CHD risk during a one year intervention study . Effects of ‘ labelling ’ were evaluated in 115 subjects with high CHD risk in comparison with a low risk reference population . The 22 participating GP centres were r and omly allocated to follow either a PCSD intervention or a CC approach . An overall satisfaction with life question was employed and psychological well-being were measured using the General Health Question naire ( 20 item version ) . Satisfaction measures on health care aspects were also included . No difference of change between the high risk and the reference population was found concerning satisfaction with life after screening . No significant difference of change was found within or between the PCSD and the CC group concerning emotional well-being or overall satisfaction with life during one year intervention . Satisfaction with the care received was significantly better in the CC group as compared with the PCSD group ( p=0.02 ) . Satisfaction with own efforts for improving health was , however , more pronounced in the PCSD group ( p=0.01 ) . A substantial number ( n=61 ) of the participants reported distaste of being reminded of the risk of heart disease and no more than 60 of the participants were satisfied with their own efforts for improving health . Although no significant change of satisfaction with life and emotional well-being due to screening or intervention could be detected , clinicians should be aware that encouraging patients to change life style may lead to patients ' annoyance of being reminded of the risk of disease and dissatisfaction with their own efforts . Increasing patient responsibility and self-determination may improve their satisfaction with their own efforts , but reduce satisfaction with medical care", "Aims There is continuing uncertainty regarding the overall net benefits of population -based screening for Type 2 diabetes . We compared clinical measures , prescribed medication , cardiovascular morbidity and self-rated health in individuals without diabetes in a screened vs. an unscreened population . Methods A parallel-group , cohort study of people aged 40–65 years , free of known diabetes , identified from the population register of a general practice in Ely , Cambridgeshire ( n = 4936 ) . In 1990–1992 , one third ( n = 1705 ) , selected r and omly , received an invitation for screening for diabetes and cardiovascular risk factors at 5-yearly intervals ( screened population ) . From the remainder of the sampling frame , 1705 r and omly selected individuals were invited to diabetes screening 10 years later ( unscreened population ) . Patients without known diabetes from both population s were invited for a health assessment . Results Of 3390 eligible individuals without diabetes , 1442 ( 43 % ) attended for health assessment , with no significant difference in attendance between groups . Thirteen years after the commencement of screening , self-rated functional health status and health utility were identical between the screened and unscreened population s. Clinical measures , self-reported medication and cardiovascular morbidity were similar between the two groups . Conclusions Screening for diabetes is not associated with long-term harms at the population level . However , screening has limited long-term impact on those testing negative ; benefits may largely be restricted to those whose diabetes is detected early through screening", "Aims We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease ( CHD ) risk could lower patients ' predicted Framingham CHD risk vs. usual care . Methods The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospect i ve , controlled , cluster-r and omised trial in nine European countries , among patients at moderate cardiovascular risk . Following baseline assessment s , physicians in the intervention group calculated patients ' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme . Usual care physicians did not calculate patients ' risk and provided usual care only . The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care . Results Of 1103 patients across 100 sites , 524 patients receiving intervention , and 461 receiving usual care , were analysed for efficacy . After 6 months , mean predicted risks were 12.5 % with intervention , and 13.7 % with usual care [ odds ratio = 0.896 ; p = 0.001 , adjusted for risk at baseline ( 17.2 % intervention ; 16.9 % usual care ) and other covariates ] . The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention ( 25.4 % ) than usual care ( 14.1 % ; p physician-implemented CHD risk evaluation/communication programme improved patients ' modifiable risk factor profile , and lowered predicted CHD risk compared with usual care . By combining this strategy with more intensive treatment to reduce residual modifiable risk , we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice", "Objective To determine the effectiveness of intensive structured care to optimise blood pressure control based on individual absolute risk targets in primary care . Design Pragmatic multicentre r and omised controlled trial . Setting General practice s throughout Australia , except Northern Territory , 2009 - 11 . Participants Of 2185 patients from 119 general practice s who were eligible for drug treatment for hypertension according to national guidelines 416 ( 19.0 % ) achieved their individual blood pressure target during a 28 day run-in period of monotherapy . After exclusions , 1562 participants not at target blood pressure ( systolic 150 ( SD 17 ) mm Hg , diastolic 88 ( SD 11 ) mm Hg ) were r and omised ( 1:2 ratio ) to usual care ( n=524 ) or the intervention ( n=1038 ) . Intervention Computer assisted clinical profiling and risk target setting ( all participants ) with intensified follow-up and stepwise drug titration ( initial angiotensin receptor blocker monotherapy or two forms of combination therapy using angiotensin receptor blockers ) for those r and omised to the intervention . The control group received usual care . Main outcome measures The primary outcome was individual blood pressure target achieved at 26 weeks . Secondary outcomes were change in mean sitting systolic and diastolic blood pressure , absolute risk for cardiovascular disease within five years based on the Framingham risk score , and proportion and rate of adverse events . Results On an intention to treat basis , there was an 8.8 % absolute difference in individual blood pressure target achieved at 26 weeks in favour of the intervention group compared with usual care group ( 358/988 ( 36.2 % ) v 138/504 ( 27.4 % ) ) : adjusted relative risk 1.28 ( 95 % confidence interval 1.10 to 1.49 , P=0.0013 ) . There was also a 9.5 % absolute difference in favour of the intervention group for achieving the classic blood pressure target of ≤140/90 mm Hg ( 627/988 ( 63.5 % ) v 272/504 ( 54.0 % ) ) : adjusted relative risk 1.18 ( 1.07 to 1.29 , P mean adjusted reduction in systolic blood pressure of 13.2 mm Hg ( 95 % confidence interval −12.3 to −14.2 mm Hg ) and diastolic blood pressure of 7.7 mm Hg ( −7.1 to −8.3 mm Hg ) v 10.1 mm Hg ( −8.8 to 11.3 mm Hg ) and 5.5 mm Hg ( −4.7 to −6.2 mm Hg ) in the usual care group ( P 1141 participants in whom five year absolute cardiovascular risk scores were calculated from baseline to the 26 week follow-up , the reduction in risk scores was greater in the intervention group than usual care group ( 14.7 % ( SD 9.3 % ) to 10.9 % ( SD 8.0 % ) ; difference −3.7 % ( SD 4.5 % ) and 15.0 % ( SD 10.1 % ) to 12.4 % ( SD 9.4 % ) ; −2.6 % ( SD 4.5 % ) : adjusted mean difference −1.13 % ( 95 % confidence interval −0.69 % to −1.63 % ; P of blood pressure control , with clinical ly lower blood pressure and absolute risk of future cardiovascular events overall and with more people achieving their target blood pressure . An important gap in treatment remains though and applying intensive management and achieving currently advocated risk based blood pressure targets is challenging", "OBJECTIVE The aim of this study was to explore beliefs and attitudes about refusing health screening in general practice . METHODS In 1991 , in Ebeltoft , Denmark people aged between 30 and 50 years were invited to participate in a 5-year r and omized , controlled , population -based project testing the value of health screenings and health discussion s in general practice . In 1994 , non- participants who declined the offered health screening but expressed willingness to be contacted in the future were asked to participate in a qualitative interview . They were drawn by stratified purpose ful sampling which reflected variation in perceived health , body mass index , age and sex . The sample comprised six men and 12 women RESULTS Some had not participated because they were busy , felt healthy or had recently been examined . The non- participants emphasized the limitations of health screening and did not want possible risk factors to be revealed , or their feeling of good health to be disturbed . They stressed the individual 's own responsibility for maintaining good health and believed that a positive attitude promoted health . They would contact their GP if they had symptoms . CONCLUSION Non- participants have rational views on risk factor testing and on their own responsibility for maintaining health . Non-attendance was due to a conscious choice which included consulting their own GP", "Aims /hypothesisThe aim of this study was to assess the impact of invitation to screening for type 2 diabetes and related cardiovascular risk factors on population mortality . Methods This was a parallel-group population -based cohort study including all men and women aged 40–65 years , free of known diabetes , registered with a single practice in Ely , UK ( n = 4,936 ) . In 1990–1992 , approximately one-third ( n = 1,705 ) were r and omly selected to receive an invitation to screening for diabetes ( with an OGTT ) and related cardiovascular risk factors . In the remaining two-thirds of the population , 1,705 individuals were r and omly selected for invitation to screening in 2000–2003 and 1,526 were not invited at any point during the follow-up period . All individuals were flagged for mortality until January 2008 . Results There were 345 deaths between 1990 and 1999 ( median 10 years follow-up ) . Compared with those not invited , individuals who were invited to the 1990–1992 screening round had a non-significant 21 % lower all-cause mortality ( HR 0.79 [ 95 % CI 0.63–1.00 ] , p = 0.05 ) after adjustment for age , sex and deprivation . There were 291 deaths between 2000 and 2008 ( median 8 years follow-up ) , with no significant difference in mortality between invited and non-invited participants in 2000–2003 . Compared with the non-invited group , participants who attended for screening at any time point had a significantly lower mortality and those who did not attend had a significantly higher mortality . Conclusions /interpretationInvitation to screening was associated with a non-significant reduction in mortality in the Ely cohort between 1990 and 1999 , but this was not replicated in the period 2000–2008 . This study contributes to the evidence concerning the potential benefits of population screening for diabetes and related cardiovascular risk factors", "South-East London Screening Study Group ( Department of Community Medicine , St Thomas 's Hospital and Medical School , London SE1 1EH , Engl and ) . A controlled trial of multiphasic screening in middle-age : results of the South-East London Screening Study . International Journal of Epidemiology 1977;6:357 - 63 . The results of a controlled trial of multiphasic screening in general practice are presented . In 1967 , 7229 individuals aged between 40 and 64 years were r and omly allocated into either a Screening or Control group . The Screening group were invited to attend two screening sessions held about two years apart , while the Control group continued to receive conventional medical care . Both groups were then invited to undergo a health survey in 1972 - 73 which revealed no significant differences in morbidity between the two groups . Careful follow-up permitted detailed Screening-Control comparisons of various outcome measures -consultation and hospital admission rates , certified sickness absence from work , and mortality . Nine years after the initial screening , no significant differences were found between the two groups in any of the outcome measures . It is estimated that a similar screening programme for the entire middle-aged UK population would cost 142 million pounds at 1976 prices", "BACKGROUND The aim of this study was to investigate the long-term effects of one general health screening on mortality . METHOD After stratification and r and omization of a population of 450,000 inhabitants , two groups were formed , an intervention group of 3064 people and a control group of 29,122 people . From the National Cause of Death Register , data were collected as regards death and causes of deaths for 1970 - 1990 . RESULTS Multivariate analysis was used to correct for known confounders . We then found no differences between the groups regarding deaths from all causes , cardiovascular diseases , cancer or accidents and poisoning . CONCLUSIONS One general health screening seems to have little , if any value in preventing fatal diseases", "Background R and omised , controlled trials focusing on long-term psychological reactions to information about increased risk of coronary heart disease are scarce . Design A population -based r and omised , controlled , 5-year follow-up trial was conducted in general practice . Methods In 1991 , invitations were sent to 2,000 middle-aged people registered in the general practice s in the district of Ebeltoft , Denmark . A total of 1,507 ( 75.4 % ) agreed to participate and were r and omised into a control group and two intervention groups : one included health screening , a written feedback and an optional follow-up visit with the general practitioner ; the other included health screening , written feedback and a planned 45-min follow-up visit with the general practitioner . The participants were informed at screening about their risk of developing coronary heart disease . Psychological distress was measured by the GHQ-12 before screening and at the 1 and the 5-year follow-up . Results Before the screening ( 0 year ) , 1 and 5 years after there were no significant differences in the GHQ-12 score between the control group and the two intervention groups . Nor were there any differences related to information about increased risk of coronary heart disease between scores obtained at the 1 and the 5-year follow-up . Conclusion Middle-aged persons had no long-term psychological reaction after information about increased risk of developing coronary heart disease following a health screening in general practice evaluated by the GHQ-12,1 year and 5 years after the examinations", "In the Study of Men Born in 1913 it was possible to investigate the influence of repeated health examinations on mortality in a prospect i ve cohort study . On January 1 , 1963 , 1010 men in the experimental grop and 1956 in the control group were alive . The experimental group took part in repeated examinations in 1963 , 1967 , 1973 and 1980 . Overt diseases were treated accordingly . Newly detected hypertension was also treated . By the end of a 15-year-long observation period , the cumulative mortality in the experimental group ( 14.5 % ) was not significantly lower than that in the control group ( 15.7 % ) . In the experimental group , 855 took part . The mortality was significantly higher in the non-participating group . The autopsy frequency decreased for in-hospital deaths but increased for deaths outside hospital during the study period", "BACKGROUND Our aim was to investigate whether a nurse-coordinated multidisciplinary , family-based preventive cardiology programme could improve st and ards of preventive care in routine clinical practice . METHODS In a matched , cluster-r and omised , controlled trial in eight European countries , six pairs of hospitals and six pairs of general practice s were assigned to an intervention programme ( INT ) or usual care ( UC ) for patients with coronary heart disease or those at high risk of developing cardiovascular disease . The primary endpoints-measured at 1 year-were family-based lifestyle change ; management of blood pressure , lipids , and blood glucose to target concentrations ; and prescription of cardioprotective drugs . Analysis was by intention to treat . The trial is registered as IS RCT N 71715857 . FINDINGS 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC , respectively . In patients with coronary heart disease who smoked in the month before the event , 136 ( 58 % ) in the INT and 154 ( 47 % ) in the UC groups did not smoke 1 year afterwards ( difference in change 10.4 % , 95 % CI -0.3 to 21.2 , p=0.06 ) . Reduced consumption of saturated fat ( 196 [ 55 % ] vs 168 [ 40 % ] ; 17.3 % , 6.4 to 28.2 , p=0.009 ) , and increased consumption of fruit and vegetables ( 680 [ 72 % ] vs 349 [ 35 % ] ; 37.3 % , 18.1 to 56.5 , p=0.004 ) , and oily fish ( 156 [ 17 % ] vs 81 [ 8 % ] ; 8.9 % , 0.3 to 17.5 , p=0.04 ) at 1 year were greatest in the INT group . High-risk individuals and partners showed changes only for fruit and vegetables ( p=0.005 ) . Blood-pressure target of less than 140/90 mm Hg was attained by both coronary ( 615 [ 65 % ] vs 547 [ 55 % ] ; 10.4 % , 0.6 to 20.2 , p=0.04 ) and high-risk ( 586 [ 58 % ] vs 407 [ 41 % ] ; 16.9 % , 2.0 to 31.8 , p=0.03 ) patients in the INT groups . Achievement of total cholesterol of less than 5 mmol/L did not differ between groups , but in high-risk patients the difference in change from baseline to 1 year was 12.7 % ( 2.4 to 23.0 , p=0.02 ) in favour of INT . In the hospital group , prescriptions for statins were higher in the INT group ( 810 [ 86 % ] vs 794 [ 80 % ] ; 6.0 % , -0.5 to 11.5 , p=0.04 ) . In general practice s in the intervention groups , angiotensin-converting enzyme inhibitors ( 297 [ 29 % ] INT vs 196 [ 20 % ] UC ; 8.5 % , 1.8 to 15.2 , p=0.02 ) and statins ( 381 [ 37 % ] INT vs 232 [ 22 % ] UC ; 14.6 % , 2.5 to 26.7 , p=0.03 ) were more frequently prescribed . INTERPRETATION To achieve the potential for cardiovascular prevention , we need local preventive cardiology programmes adapted to individual countries , which are accessible by all hospitals and general practice s caring for coronary and high-risk patients", "Within a community-wide heart disease prevention effort , it was hypothesized that personalized risk factor screening and education would result in modified health behaviors and reduced risk factor levels for coronary heart disease . Adults from a population sample were r and omized to a community-wide screening and education program or were excluded from that program for 1 year . At the end of that year , both groups were measured for risk factor levels and related health behaviors . Those who received the screening and education program had significantly lower risk factor levels and other evidence of health behavior change , including lower blood cholesterol ( 206.9 vs 211.5 mg/dl ) , lower diastolic blood pressure ( 68.7 vs 70.0 mm Hg ) , lower resting heart rate ( 71.4 vs 72.7 bpm ) , and increased selection of low-fat and low-sodium meals in local restaurants . These data suggest that systematic risk factor screening and education may result in lower population risk for coronary heart disease" ]	4118412c-06ff-11f0-808a-c43d1ab1c353
Background and Purpose — Obesity is a risk factor for all-cause and cardiovascular death but , despite this , an inverse relationship between overweight or obesity and a better cardiovascular prognosis in long-term follow-up studies has been observed ; this phenomenon , described as obesity paradox , has also been found evident in atrial fibrillation cohorts . Methods — We performed a systematic review on the relationship between body mass index and major adverse outcomes in atrial fibrillation patients . Moreover , we provided a meta- analysis of non – vitamin K antagonist oral anticoagulants ( NOACs ) trials . Results — An obesity paradox was found for cardiovascular death and all-cause death in the subgroup analyses of r and omized trial cohorts ; however , observational studies fail to show this relationship . From the meta- analysis of NOAC trials , a significant obesity paradox was found , with both overweight and obese patients reporting a lower risk for stroke/systemic embolic event ( odds ratio [ OR ] , 0.75 ; 95 % confidence interval [ CI ] , 0.66–0.84 and OR , 0.62 ; 95 % CI , 0.54–0.70 , respectively ) . For major bleeding , only obese patients were at lower risk compared with normal weight patients ( OR , 0.84 ; 95 % CI , 0.72–0.98 ) . A significant treatment effect of NOACs was found in normal weight patients , both for stroke/systemic embolic event ( OR , 0.66 ; 95 % CI , 0.56–0.78 ) and for major bleeding ( OR , 0.72 ; 95 % CI , 0.54–0.95 ) . Major bleeding risk was lower in overweight patients treated with NOACs ( OR , 0.84 ; 95 % CI , 0.71–1.00 ) . Conclusions — There may be an obesity paradox in atrial fibrillation patients , particularly for all-cause and cardiovascular death outcomes . An obesity paradox was also evident for stroke/systemic embolic event outcome in NOAC trials , with a treatment effect favoring NOACs over warfarin for both efficacy and safety that was significant only for normal weight patients	[ "BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P dabigatran ( P mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 .", "BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . )", "Background —Physical activity ( PA ) has previously been suggested to attenuate the risk of atrial fibrillation ( AF ) conferred by excess body weight and weight gain . We prospect ively examined the relationship between body size , weight change , and level of PA in a biracial cohort of middle-aged men and women . Methods and Results —Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study . AF incidence was ascertained from 1987 to 2009 . Adjusted Cox proportional hazards models were used to estimate the associations between body mass index , waist circumference , relative weight change , and PA level with incident AF . During follow-up , there were 1775 cases of incident AF . Body mass index and waist circumference were positively associated with AF as was weight loss/gain of > 5 % initial body weight . An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women : compared with men with a normal body mass index , the risk of AF in obese men with an ideal , intermediate , and poor level of PA at baseline was increased by 37 % , 129 % , and 156 % ( Pinteraction=0.04 ) . During follow-up , PA did not modify the association between weight gain and risk of AF . Conclusions —Obesity and extreme weight change are risk factors for incident AF , whereas being physically active is associated with a small reduction in risk . In men only , being physically active offset some , but not all , of the risk incurred with excess body weight", "BACKGROUND Obese patients have favorable outcomes in congestive heart failure , hypertension , peripheral vascular disease , and coronary artery disease . Obesity also has been linked with increased incidence of atrial fibrillation , but its influence on outcomes in atrial fibrillation patients has not been investigated . The objective of this research is to investigate the effect of obesity on outcomes in atrial fibrillation . METHODS The Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study was one of the largest multicenter trials of atrial fibrillation , with 4060 patients . Subjects were r and omized to rate versus rhythm-control strategy . We performed a post hoc analysis of the National Heart , Lung and Blood Institute limited access data set of atrial fibrillation patients who had body mass index ( BMI ) data available in the AFFIRM study . BMI data were not available on 1542 patients . Patients with BMI > or=18.5 were split into normal ( 18.5 - 25 ) , overweight ( 25 - 30 ) , and obese ( > 30 ) categories as per BMI ( kg/m(2 ) ) . Multivariate Cox proportional hazards regression was used on the eligible 2492 patients . End points were all-cause mortality and cardiovascular mortality . RESULTS Over three fourths of all patients in our cohort were overweight or obese . There were 304 deaths ( 103 among normal weight , 108 among overweight , and 93 among obese ) and 148 cardiovascular deaths ( 54 among normal weight , 41 among overweight , and 53 among obese ) over a mean period of 3 years of patient follow-up . On multivariate analysis , overweight ( hazard ratio [ HR ] 0.64 ; 95 % confidence interval [ CI ] , 0.48 - 0.84 ; P=.001 ) and obese ( HR 0.80 ; 95 % CI , 0.68 - 0.93 ; P=.005 ) categories were associated with lower all-cause mortality as compared with normal weight . Overweight ( HR 0.40 ; 95 % CI , 0.26 - 0.60 ; P cardiovascular mortality as compared with the normal weight patients . CONCLUSIONS Although in prior studies , obesity has been associated with increased risk of atrial fibrillation , an obesity paradox exists for outcomes in atrial fibrillation . Obese patients with atrial fibrillation appear to have better long-term outcomes than nonobese patients", "BACKGROUND Japanese patients with atrial fibrillation ( AF ) are generally small and lean , but knowledge of the clinical characteristics of those with low body weight ( LBW : ≤50 kg ) is limited . METHODS AND RESULTS The Fushimi AF Registry is a community-based prospect i ve survey of AF patients who visited the participating medical institutions in Fushmi-ku , Japan . The BW and follow-up data were available for 2,945 patients . We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group . Patients in the LBW group accounted for 26.8 % ( 788 patients ) of the total . The LBW group was more often female , older , and had higher CHADS2score . The incidence of stroke/systemic embolism ( SE ) during follow-up was higher in the LBW group ( hazard ratio ( HR ) : 2.19 , 95 % confidence interval ( CI ) : 1.57 - 3.04 ; P that of major bleeding was comparable ( HR : 1.05 , 95 % CI : 0.64 - 1.68 ; P=0.84 ) . This trend was consistently observed in the subgroups stratified by age , sex , and oral anticoagulant prescription at baseline . Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE . CONCLUSIONS Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE , but the incidence of major bleeding was not particularly high", "BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment . Rivaroxaban , an oral factor Xa inhibitor , may provide more consistent and predictable anticoagulation than warfarin . METHODS In a double-blind trial , we r and omly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban ( at a daily dose of 20 mg ) or dose-adjusted warfarin . The per- protocol , as-treated primary analysis was design ed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism . RESULTS In the primary analysis , the primary end point occurred in 188 patients in the rivaroxaban group ( 1.7 % per year ) and in 241 in the warfarin group ( 2.2 % per year ) ( hazard ratio in the rivaroxaban group , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.96 ; P rivaroxaban group ( 2.1 % per year ) and in 306 patients in the warfarin group ( 2.4 % per year ) ( hazard ratio , 0.88 ; 95 % CI , 0.74 to 1.03 ; P Major and nonmajor clinical ly relevant bleeding occurred in 1475 patients in the rivaroxaban group ( 14.9 % per year ) and in 1449 in the warfarin group ( 14.5 % per year ) ( hazard ratio , 1.03 ; 95 % CI , 0.96 to 1.11 ; P=0.44 ) , with significant reductions in intracranial hemorrhage ( 0.5 % vs. 0.7 % , P=0.02 ) and fatal bleeding ( 0.2 % vs. 0.5 % , P=0.003 ) in the rivaroxaban group . CONCLUSIONS In patients with atrial fibrillation , rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism . There was no significant between-group difference in the risk of major bleeding , although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group . ( Funded by Johnson & Johnson and Bayer ; ROCKET AF Clinical Trials.gov number , NCT00403767 . )", "AIM Explore the relation between body mass index ( BMI ) and cardiovascular disease , and the influence of optimal medical therapy ( OMT ) on this relationship . METHODS AND RESULTS Patients from the REACH cohort , an international , prospect i ve cohort of patients with or at high risk of atherosclerosis with documentation of potential confounders , including treatments and risk factors , were followed up to 4 years ( n = 54 285 ) . Patients were categorized according to baseline BMI ( ranging from underweight to Grade III obesity ) . Optimal medical therapy was defined as the use of the four cardioprotective medication classes ( statins , ACE inhibitors/angiotensin II receptor blockers , β-blockers , and antiplatelet agents ) . The main outcomes were all-cause mortality , cardiovascular ( CV ) mortality , and CV events . In primary and secondary prevention , a reverse J-shaped curve best described the relationship between BMI categories and the incidence of the various outcomes . In secondary prevention , the highest adjusted risks were observed for underweight patients ( 1.97 , P CV mortality and CV events ) and the lowest HRs were observed , respectively , in Grade II and Grade III obese patients ( 0.73 , P proportion of patients on OMT increased with BMI from 10.1 to 36 % ( P CV protection conferred by obesity persisted in patients receiving OMT . CONCLUSION An obesity paradox was observed in both primary and secondary CV prevention patients . The intensity of use of evidence -based preventive medications does not account for the paradoxical CV protection associated with obesity . At extremes of BMI , further interventions beyond OMT may be needed to reduce CV risk", "Atrial fibrillation ( AF ) and obesity have reached epidemic proportions . The impact of obesity on clinical outcomes in patients with established AF is unknown . We analyzed 2,492 patients in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management ( AFFIRM ) study . Body mass index ( BMI ) was evaluated as a categorical variable ( normal 18.5 to or=30 kg/m(2 ) ) . Rate of death from any cause was higher in the normal BMI group ( 5.8 per 100 patient-years ) than in the overweight and obese groups ( 3.9 and 3.7 , respectively ) . Cardiovascular death rate was highest in the normal BMI group ( 3.1 per 100 patient-years ) , lowest in the overweight group ( 1.5 per 100 patient-years ) , and intermediate in the obese group ( 2.1 per 100 patient-years ) . After adjustment for baseline factors , differences in risk of death from any cause were no longer significant . However , overweight remained associated with a lower risk of cardiovascular death ( hazard ratio 0.47 , p = 0.002 ) . Obese patients were more likely to have an uncontrolled heart rate at rest , but rhythm-control strategy success was similar across BMI categories . In each BMI category , risk of death from any cause was similar for patients r and omized to a rhythm- or rate-control strategy . In conclusion , in patients with established AF , overweight and obesity do not adversely affect overall survival . Obesity does not appear to affect the relative benefit of a rate- or rhythm-control strategy", "BACKGROUND Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations . Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin . METHODS In this r and omized , double-blind trial , we compared apixaban ( at a dose of 5 mg twice daily ) with warfarin ( target international normalized ratio , 2.0 to 3.0 ) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke . The primary outcome was ischemic or hemorrhagic stroke or systemic embolism . The trial was design ed to test for noninferiority , with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause . RESULTS The median duration of follow-up was 1.8 years . The rate of the primary outcome was 1.27 % per year in the apixaban group , as compared with 1.60 % per year in the warfarin group ( hazard ratio with apixaban , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.95 ; P rate of major bleeding was 2.13 % per year in the apixaban group , as compared with 3.09 % per year in the warfarin group ( hazard ratio , 0.69 ; 95 % CI , 0.60 to 0.80 ; P rates of death from any cause were 3.52 % and 3.94 % , respectively ( hazard ratio , 0.89 ; 95 % CI , 0.80 to 0.99 ; P=0.047 ) . The rate of hemorrhagic stroke was 0.24 % per year in the apixaban group , as compared with 0.47 % per year in the warfarin group ( hazard ratio , 0.51 ; 95 % CI , 0.35 to 0.75 ; P rate of ischemic or uncertain type of stroke was 0.97 % per year in the apixaban group and 1.05 % per year in the warfarin group ( hazard ratio , 0.92 ; 95 % CI , 0.74 to 1.13 ; P=0.42 ) . CONCLUSIONS In patients with atrial fibrillation , apixaban was superior to warfarin in preventing stroke or systemic embolism , caused less bleeding , and result ed in lower mortality . ( Funded by Bristol-Myers Squibb and Pfizer ; ARISTOTLE Clinical Trials.gov number , NCT00412984 . )", "Obesity is well-established as a major cardiovascular ( CV ) risk factor . Obesity confers a greater risk for developing atrial fibrillation ( AF ) , but the relation between obesity and established nonvalvular AF for stroke and all-cause death is still unclear . To ascertain the prevalence of overweight and obesity in patients with nonvalvular AF , their influence on adverse events , and the relation with anticoagulation control , we performed this post hoc analysis of the pooled Stroke Prevention using an Oral Thrombin Inhibitor in patients with atrial Fibrillation ( SPORTIF ) III and V data sets . For this study , we analyzed all patients assigned to the warfarin arm with data on body mass index ( BMI ) . Time in therapeutic range was used as an index of the quality of anticoagulation control . The 3,630 patients eligible for this analysis were categorized as follows : ( 1 ) BMI 18.5 to 24.9 ( \" normal weight \" ) in 24.1 % ; ( 2 ) BMI 25.0 to 29.9 ( \" overweight \" ) in 39.8 % ; and BMI ≥30 ( \" obese \" ) in 36.1 % . Both overweight ( hazard ratio [ HR ] 0.70 ) and obese ( HR 0.59 ) categories were inversely associated with the composite outcome of stroke/all-cause death . A similar inverse association was seen for the end point of stroke ( HR 0.61 and 0.47 , respectively ) . Good anticoagulation control also attenuated the association between BMI categories and outcomes . In patients with time in therapeutic range > 70 % , BMI category was not significantly associated with the composite outcome of stroke/death and stroke . Stroke and all-cause death progressively reduced in overweight and obese anticoagulated patients with AF . The inverse relation of BMI categories to the risk of stroke and all-cause death was mitigated by good anticoagulation control", "BACKGROUND Obesity is associated with the development of atrial fibrillation and may impact atrial fibrillation-related outcomes . To date , no anthropometric measure is included in any risk stratification scheme for stroke and death in atrial fibrillation patients . METHODS The prospect i ve Danish Diet , Cancer and Health study is a cohort including 57,053 participants ( 27,178 men and 29,875 women ) aged between 50 and 64 years . The study population for this study included the 3135 patients ( 2025 men and 1110 women ) who developed incident atrial fibrillation during follow-up . RESULTS Of the subjects with atrial fibrillation , 1414 ( 45 % ) had a body mass index ( BMI ) in the overweight category ( BMI 25 to 30 kg/m(2 ) ) and 767 ( 24 % ) were categorized as obese ( BMI ≥30 kg/m(2 ) ) . During a median follow-up of 4.9 years , 609 deaths and 216 thromboembolic events ( 98 % ischemic strokes ) occurred . Using normal-weight patients as reference , the risk of a composite end point of \" ischemic stroke , thromboembolism , or death \" was significantly higher in overweight ( crude hazard ratio [ HR ] 1.31 ; 95 % confidence interval [ CI ] , 1.09 - 1.56 ) and obese patients ( crude HR 1.55 ; 95 % CI 1.27 - 1.90 ) . After adjustment for CHADS2 and CHA2DS2-VASc scores , the HRs for the composite end point were 1.21 ( 95 % CI 1.02 - 1.45 ) and 1.31 ( 95 % CI 1.10 - 1.56 ) , respectively , for overweight and 1.25 ( 95 % CI 1.03 - 1.53 ) and 1.36 ( 95 % CI 1.11 - 1.65 ) , respectively , for obese . Continuous analyses of BMI stratified by sex identified obese men and normal-weight women as the sex-specific \" high-risk \" categories . CONCLUSION Overweight and obesity are risk factors for \" ischemic stroke , thromboembolism or death \" in patients with atrial fibrillation , even after adjustment for CHADS2 and CHA2DS2-VASc scores . The association between BMI and outcomes among atrial fibrillation patients may be modified by sex" ]	411841ae-06ff-11f0-808a-c43d1ab1c353
Background Physical fitness during childhood and adolescence has been identified as an important determinant of current and future health status . While research has traditionally focused on the association between cardio-respiratory fitness and health outcomes , the association between muscular fitness ( MF ) and health status has recently received increased attention . Objective The aim of this systematic review and meta- analysis was to evaluate the potential physiological and psychological benefits associated with MF among children and adolescents . Methods A systematic search of six electronic data bases ( PubMed , SPORTD iscus , Scopus , EMBASE , PsycINFO and OVID MEDLINE ) was performed on the 20th May , 2013 . Cross-sectional , longitudinal and experimental studies that quantitatively examined the association between MF and potential health benefits among children and adolescents were included . The search yielded 110 eligible studies , encompassing six health outcomes ( i.e. , adiposity , bone health , cardiovascular disease [ CVD ] and metabolic risk factors , musculoskeletal pain , psychological health and cognitive ability ) . The percentage of studies reporting statistically significant associations between MF and the outcome of interest was used to determine the strength of the evidence for an association and additional coding was conducted to account for risk of bias . Meta-analyses were also performed to determine the pooled effect size if there were at least three studies providing st and ardised coefficients . Results Strong evidence was found for an inverse association between MF and total and central adiposity , and CVD and metabolic risk factors . The pooled effect size for the relationship between MF and adiposity was r = −0.25 ( 95 % CI −0.41 to −0.08 ) . Strong evidence was also found for a positive association between MF and bone health and self-esteem . The pooled effect size for the relationship between MF and perceived sports competence was r = 0.39 ( 95 % CI 0.34–0.45 ) . The evidence for an association between MF and musculoskeletal pain and cognitive ability was inconsistent/uncertain . Where evidence of an association was found , the associations were generally low to moderate . Conclusion The findings of this review highlight the importance of developing MF in youth for a number of health-related benefits	[ "PURPOSE The purpose of this study was to describe levels of inflammation markers in Norwegian children and to examine the associations of adiposity , aerobic fitness , and muscle fitness with markers of inflammation . METHODS In 2005 - 2006 , 1467 nine-year-olds were r and omly selected from all regions in Norway . The participation rate was 89 % . The inflammatory markers evaluated included C-reactive protein ( CRP ) , leptin , adiponectin , plasminogen activator inhibitor-1 , tumor necrosis factor-α , hepatocyte growth factor , resistin , and interleukin-6 . We assessed muscular strength by measuring explosive , isometric , and endurance strength . Aerobic fitness was measured directly during a maximal cycle ergometer test . Adiposity was expressed as waist circumference ( WC ) . RESULTS The girls had significantly higher levels of CRP , leptin , adiponectin , and resistin and lower levels of tumor necrosis factor-α compared with the boys . We observed a grade d association of CRP and leptin levels across quintiles of WC , aerobic fitness , and muscle fitness ( P ≤ 0.001 for all participants ) . The regression analyses revealed that WC , aerobic fitness , and muscle fitness were independently associated with the CRP ( WC β = 0.158 , P for leptin levels ( WC β = 0.406 , P the CRP and leptin levels ", "Our aim is to analyse the effect on bone mass of : ( 1 ) physical fitness performance on a specific group of physical activity ( PA ) and , ( 2 ) PA on a specific physical fitness performance group . Bone mineral content ( BMC ) by dual energy X-ray absorptiometry ( DXA ) and PA by accelerometers was assessed in 373 Spanish adolescents ( 182 males ) . Adolescents were classified as : active and non-active ( ≥60 or of moderate-vigorous PA ) . Fitness was assessed through speed/agility , strength and cardiorespiratory tests . Adolescents were classified by tertiles ( T1 , T2 and T3 ) . ANCOVA was used for the analysis with sex , height , lean mass , calcium intake and pubertal status as covariates . Adolescents with lower strength , speed/agility and cardiorespiratory fitness ( CRF ) showed lower BMC in the whole body and extremities compared with adolescents with better results in these tests , mainly those non-active adolescents . Non-active adolescents with high fitness levels showed higher BMC ( whole body and upper limbs ) than active ones . The conclusions included : ( 1 ) within the non-active group , lower levels of fitness were associated with lower BMC ; this might be through PA or trough an effect of PA on muscle mass . ( 2 ) Non-active adolescents with high level of fitness in most fitness tests showed higher BMC than their active peers , in spite of their lower PA levels . These unexpected results could be influenced by several factors such as genetics , nutrition , type of exercise or sport , hormones and skeletal age", "OBJECTIVE The purpose of this study was to examine differences in cardiovascular disease ( CVD ) risk factors across four cross-tabulated groups of cardiorespiratory fitness and body mass index in 8- to 18-year-old children and adolescents . METHODS The sample included 296 boys and 188 girls ( mean age=15.7 years ) participating in the Aerobics Center Longitudinal Study . Participants were cross tabulated into four groups using a median split of age-adjusted treadmill time to exhaustion ( TM ) and body mass index ( BMI ) . Group differences in CVD risk factors ( blood pressure [ BP ] , fasting total cholesterol [ TC ] , low density lipoprotein-cholesterol [ LDL-C ] , high density lipoprotein-cholesterol [ HDL-C ] , TC : HDL-C , triglycerides [ TG ] , glucose , and a metabolic syndrome score ) were examined by ANCOVA , controlling for age . RESULTS In males , significant differences across groups were observed for systolic BP , mean arterial pressure ( MAP ) , TC , LDL-C , TC : HDL-C and the metabolic syndrome score ( p TG was significantly different across groups ( p DBP and TG in males ( p=0.09 to 0.11 ) and diastolic BP , MAP , HDL-C , and the metabolic syndrome score in females ( p=0.14 to 0.16 ) . In general , males and females in the low BMI group , either fit or unfit , had lower BP and blood lipid values than those in the high BMI group . In both sexes , the high BMI /low fit group had the highest ( most adverse ) metabolic syndrome score . CONCLUSION This study utilized a unique approach to examine the possible interaction of fitness and fatness on CVD risk factors in children and adolescents . The results provide some evidence for the consideration of both variables when interpreting CVD risk factors in young people", "Aims : To investigate how physical activity , physical performance and sociodemographic characteristics at the age of 16 are related to adult health habits ( physical activity , dietary intake , smoking ) and biological risk factors for cardiovascular diseases ( being overweight , low aerobic fitness , unfavorable levels of serum lipids , high blood pressure ) . Methods : A r and omly selected group of 220 male and 205 female students at 16 years of age was tested in 1974 , and reinvestigated 18 years later . Results : The predictive health profiles for adult lifestyle and biological risk factors were different in men and women . Leisure sports activity along with high performance in the nine-minute run among the boys and in the two-h and lift test among the girls were significant predictors of adult physical activity . A positive attitude to aerobic exercise and high performance in the nine-minute run test among the boys and high marks in physical education among the girls decreased the risk of smoking . Leisure sports activities together with body mass index at young ages were the most powerful predictors of adult biological risk factors , but attitudes to sports and educational level were also significant determinants . Conclusion : These results contribute to the knowledge of which factors at young ages may promote adult healthy habits in particular physical activities ", "Cardiovascular disease is recognized as a serious public health problem . Because the underlying pathological processes start shortly after birth , tracking of recognized cardiovascular disease indicators during childhood and adolescence can help in developing preventive pediatric strategies . A prospect i ve follow-up of both genetic and behavioral lifestyle parameters ( serum cholesterol , blood pressure , percentage body fat , maximal oxygen uptake ( VO2max ) , smoking , physical inactivity , and type A behavior ) was design ed . In the Amsterdam Growth and Health Study a population of 93 males and 107 females was measured annually from 1977 to 1980 and a fifth measurement was made in 1985 . In that way longitudinal data covering a period of 8 years was collected for a group of adolescents/adults between 13 and 21 years of age . Analyses of these parameters provided the following results : The stability over the 9 years of tracking cardiovascular disease indicators , measured as the interperiod correlations , is fairly high . It varies from 0.4 to 0.8 in percentage body fat , cholesterol , and VO2max . Blood pressure values are low ( between 0.3 and 0.4 ) . The probability of 13-year-olds having relatively high values of cardiovascular disease indicators on the basis of a quartile distribution with that at age 21 indicated a moderate to high predictive value . According to the literature , the levels of subjects that are continuously relatively high over the years are more in the direction of optimal health than risk values . The exception is for percentage body fat . Interrelation of the seven cardiovascular disease indicators in constantly relatively high-risk and relatively low-risk groups during the teenage period , measured during young adulthood ( 21.5 years ) , appeared to be weak : only males and females with a high percentage body fat and a low VO2max showed significantly high total cholesterol , low high-density lipoprotein cholesterol , and high total cholesterol/high-density lipoprotein cholesterol levels . From the three environmental cardiovascular disease indicators ( smoking , physical activity , and type A/B behavior ) measured in 1985 , only physical activity was significantly correlated among males and females with high-density lipoprotein cholesterol , percentage body fat , and VO2max . It can be concluded that measurement of percentage body fat in the early teenage period seems to be the most important cardiovascular disease indicator in predicting risk levels in the young adult . The amount of physical activity measured at young adult age is the only behavioral parameter to show a significant interrelation with other cardiovascular disease risk indicators . ( ABSTRACT TRUNCATED AT 400 WORDS", "BACKGROUND Childhood obesity has been inconsistently associated with decreased levels of physical activity and fitness . Moreover , little is known about this relationship among Filipino preteens . METHODS This cross sectional study reports the association between childhood obesity , measures of physical activity , and fitness . Children aged 11 to 12 from r and omly selected schools from San Juan , Metromanila were included . Outcome measures were body mass index , Filipino modified Physical Activity Question naire for Older children ( F_PAQ-C ) , st and ing broad jump , 50 m sprint and 20 m multistage shuttle run . RESULTS 380 children participated in the study . Obese children had significantly lower median scores in the F_PAQ-C compared with overweight children . Overweight children had lower scores in the st and ing broad jump , 50 m sprints and predicted VO2max as compared with children with normal BMI . There were modest associations between the 50 m sprint , predicted VO2max , and F_PAQ-C. CONCLUSION Our study has showed that physical activity and fitness scores were strongly correlated with childhood obesity . If childhood physical fitness is a predictor of physical fitness in adulthood which is a risk factor in cardiovascular diseases , there is a strong possibility that the prevalence of cardiovascular disease in the Philippines will increase dramatically in the future", "OBJECTIVES We sought to characterize the impact of obesity on vascular function in adolescents and to determine whether an exercise program reverses abnormalities in endothelial function . BACKGROUND Obesity , a major modifiable risk factor for cardiovascular disease , is epidemic in Western societies , with rapid rates of increase in the young . Atherosclerosis begins in childhood , and endothelial dysfunction is its earliest detectable manifestation . METHODS The influence of eight weeks of circuit training ( CT ) was examined in 19 obese subjects ( 14.3 + /- 1.5 years ) , using a r and omized , crossover protocol . Functional capacity and muscular strength were assessed by st and ard techniques . Body composition was examined using anthropometric measures and dual-energy X-ray absorptiometry . Conduit vessel endothelial function was assessed using high-resolution ultrasound and flow-mediated dilation ( FMD ) of the brachial artery . RESULTS Circuit training decreased abdominal and trunk fat and significantly improved fitness and muscular strength ( p obese group , FMD was significantly impaired relative to control subjects ( n = 20 ) at entry ( 5.3 + /- 0.9 % vs. 8.9 + /- 1.5 % , p Circuit training improved functional capacity , muscular strength , and body composition in obese adolescents . Furthermore , conduit vessel function was normalized after exercise training . If vascular dysfunction is an integral component of the pathogenesis of vascular disease , this study supports the value of an exercise program in the management of obese adolescents", "ABSTRACT The primary purpose of this study was to compare two mother-daughter interventions design ed to increase fitness and activity and improve physical self-perception ( PSP ) . A secondary purpose was to test two of the proposed mechanisms for using physical activity to enhance PSP . Twenty mother-daughter pairs ( n = 40 ) were r and omly assigned to a university-based ( UB ) or home-based ( HB ) group . Initially , both groups received classroom training design ed to improve PSP . Then , the UB group met three times per week , whereas the HB group received information concerning home-based activities . The Fitnessgram ® activity question naire and fitness test battery were used to measure physical activity and fitness level . The Physical Self-Perception Profile ( PSPP ) was used to detect changes in PSP . Separate 2 ( group ) × 2 ( age ) × 2 ( time ) ANOVAs with repeated measures on the last factor were conducted to examine changes in PSP , physical activity , and fitness . Correlations between physical activity , fitness , and PSP were examined to test the two mechanisms . Perceived sports competence and body attractiveness improved in UB and HB mothers and daughters ( p = .002 and .005 , respectively ) . UB and HB mothers and daughters increased their participation in aerobic ( p = .000 and .015 ) , muscular strength ( p = .001 and .001 ) , and flexibility ( p = .000 and .000 ) activities . Support was not provided for the proposed mechanisms for the relationship between physical activity and PSP . These interventions demonstrate the potential to foster positive short-term changes in PSP and physical activity in mothers and daughters . More research is needed to test mechanisms explaining the relationship between activity and PSP", "PURPOSE This study was conducted to determine the effect of physical education class enrollment and physical activity on academic achievement in middle school children . METHODS Participants were 214 sixth- grade students r and omly assigned to physical education during either first or second semesters . Moderate and vigorous physical activity ( MVPA ) ( number of 30-min time blocks ) outside of school was assessed using the 3-d physical activity recall ( 3DPAR ) . The 3DPAR time blocks were converted to ordinal data with scores of 1 ( no activity ) , 2 ( some activity ) , or 3 ( activity meeting Healthy People 2010 guidelines ) . Academic achievement was assessed using grade s from four core academic classes and st and ardized test scores ( Terra Nova percentiles ) . RESULTS Grade s were similar regardless of whether students were enrolled in physical education during first or second semesters . Physical education classes averaged only 19 min of MVPA . Students who either performed some or met Healthy People 2010 guidelines for vigorous activity had significantly higher grade s ( P grade s. St and ardized test scores were not significantly related to physical education class enrollment or physical activity levels . CONCLUSION Although academic achievement was not significantly related to physical education enrollment , higher grade s were associated with vigorous physical activity , particularly activity meeting recommended Healthy People 2010 levels", "The POWER PE study was an 8-mo , r and omized , controlled , school-based exercise intervention design ed to apply known principles of effective bone loading to practical opportunities to improve life-long musculoskeletal outcomes . A total of 99 adolescents ( 46 boys and 53 girls ) with a mean age of 13.8 + /- 0.4 yr ( peri- to postpubertal ) volunteered to participate . Intervention subjects performed 10 min of jumping activity in place of regular physical education ( PE ) warm up . Control subjects performed usual PE warm-up activities . Bone mass ( DXA and QUS ) was assessed at baseline and follow-up along with anthropometry , maturity , muscle power , and estimates of physical activity and dietary calcium . Geometric properties ( such as femoral neck [ FN ] moment of inertia ) were calculated from DXA measures . Boys in the intervention group experienced improvements in calcaneal broadb and ultrasound attenuation ( BUA ) ( + 5.0 % ) and fat mass ( -10.5 % ) , whereas controls did not ( + 1.4 % and -0.8 % , respectively ) . Girls in the intervention group improved FN BMC ( + 13.9 % ) and lumbar spine ( LS ) BMAD ( + 5.2 % ) more than controls ( + 4.9 % and + 1.5 % , respectively ) . Between-group comparisons of change showed intervention effects only for whole body ( WB ) BMC ( + 10.6 % versus + 6.3 % ) for boys . Boys in the intervention group gained more lean tissue mass , trochanter ( TR ) BMC , LS BMC , and WB BMC and lost more fat mass than girls in the intervention group ( p bone accrual in a sex-specific manner . Boys increased WB bone mass and BUA , and reduced fat mass , whereas girls improved bone mass at the hip and spine", "Background Whether muscle strength in youth is related to cardiovascular risk later in life independent of cardiorespiratory fitness is unclear . Methods We examined the independent association of isometric muscle strength in youth with cardiovascular risk factors in young adulthood using data from the Danish European Youth Heart Study ; a population -based prospect i ve cohort study among boys and girls ( n=332 ) followed for up to 12 years . In youth maximal voluntary contractions during isometric back extension and abdominal flexion were determined using a strain-gauge dynamometer and cardiorespiratory fitness was obtained from a maximal cycle ergometer test . Cardiovascular risk factors were obtained in youth and in young adulthood . Associations were examined using multivariable-adjusted regression models including major confounding factors . Results Each 1 SD difference in isometric muscle strength in youth ( 0.17 N/kg ) was inversely associated with body mass index ( BMI ; −0.60 kg/m2 , 95 % CI −0.97 to −0.22 ) , triglyceride ( −0.09 mmol/l , 95 % CI −0.16 to −0.02 ) , diastolic blood pressure ( BP ) ( −1.22 mm Hg , 95 % CI −2.15 to −0.29 ) and a composite cardiovascular risk factor score ( −0.61 SD , 95 % CI −1.03 to −0.20 ) in young adulthood in multivariable-adjusted analyses including fitness . Associations to triglyceride , diastolic BP and the cardiovascular risk factor score remained with additional adjustment for waist circumference or BMI . Each 1 SD difference in isometric muscle strength in youth was significantly associated with 0.59 ( 95 % CI 0.40 to 0.87 ) lower odds of general overweight/obesity in young adulthood ( p=0.007 ) and was marginally associated with incident raised BP , raised triglyceride and low high-density lipoprotein cholesterol . Conclusions This study suggests that greater isometric muscle strength in youth is associated with lower levels of cardiovascular risk factors in young adulthood independent of fitness , adiposity and other confounding factors", "OBJECTIVE : To study the effect of physical activity on whole body fat ( BF ) , its regional deposition and the influence of body fatness on physical performance in prepubertal children . DESSIGN : Cross-sectional study .SUBJECTS : A total of 114 boys ( 9.4±1.5 y , Tanner I – II ) , r and omly sample d from the population of Gran Canaria ( Spain ) , 63 of them physically active ( PA , at least 3 h per week during the previous year ) and 51 nonphysically active ( non-PA ) . MEASUREMENTS : Body composition ( DXA ) , anthropometric variables ( body circumferences and skinfolds ) and physical fitness were determined in all subjects . RESULTS : The PA obtained better results in maximal oxygen uptake , isometric leg extension force , vertical jump ( muscular power ) , and 300 m ( anaerobic capacity ) and 30 m running tests ( speed ) than the non-PA . A lower percentage of body fat ( % BF ) ( 4 U less , P whole BF mass ( 36 % less , P and regional fat mass ( 28 , 25 , and 30 % less in the trunk , legs and arms , respectively , all P the PA compared to the non-PA . The waist and hip circumferences correlated more closely with both the fat mass accumulated in the trunk region and the % BF ( r=0.81–0.95 , P the waist-to-hip ratio ( WHR ) . The WHR correlated with the percentage of the whole fat mass accumulated in the trunk ( PFT ) ( r=0.52–0.53 , P the PFT increased curvilinearly with the % BF , regardless of the level of physical activity . ANCOVA analysis revealed that total and regional fat masses explained less than 40 % of the difference in performance between the PA and non-PA group . The mean speed in the 30 m running test ( V30 ) , combined with the height and whole body mass , has predictive value for the BF mass ( R=0.98 , P The % BF may be estimated from the body mass index ( BMI ) and V30 ( % BF=8.09 + 2.44 · BMI ( kg m−2)–5.8·V30 ( m s−1 ) , R=0.94 , P sports activities and competitions on top of the compulsory physical education program is associated with increased physical fitness , lower whole body and trunkal fat mass in prepubertal boys", "Objectives To describe the risk factors associated with injuries result ing from physical education ( PE ) , leisure time physical activity ( leisure time PA ) and sports in 9–12-year-old children . Design Prospect i ve cohort study . Setting Primary schools . Participants Nine hundred and ninety-five children aged 9–12 years . Main outcome measures Injuries occurring during either PE class , leisure time PA or sports , and caused the child to at least stop the current activity were recorded prospect ively . Individual weekly exposure was estimated from baseline and follow-up question naires . Potential risk factors were gender , age , socioeconomic status , ethnicity , habitual level of PA , body mass index and a motor fitness . A multivariate Cox proportional hazard regression model was developed , accounting for clustering within schools . Results Gender , age and level of PA were independent significant risk factors for injury . Different modalities of PA had different injury risk factors . Most importantly , the low levels of habitual PA significantly increased injury risk . Conclusions The children at highest injury risk are the target audience of the contemporary PA promotion efforts . PA promotion should also focus on injury prevention", "This study evaluates the effect of physical activity on the bone content ( BMC ) and density ( BMD ) in 51 girls ( 14.2+/-0.4 yr ) . Twenty-four were placed in the h and ball group as they have been playing h and ball for at least 1 year ( 3.9+/-0.4 ) . The other 27 who did not perform in any kind of regular physical activity other than that programmed during the compulsory physical education courses comprised the control group . Bone mass and areal density were measured by dual-energy X-ray absorptiometry ( DXA ) . The maximal leg extension isometric force in the squat position with knees bent at 90 degrees and the peak force , mean power , and height jumped during vertical squat jump were assessed with a force plate . Additionally , 30-m run ( running speed ) and 300-m run ( as an estimate of anaerobic capacity ) tests were also performed . Maximal aerobic capacity was estimated using the 20-m shuttle-run tests . Compared to the controls , h and ballers attained better results in the physical fitness tests and had a 6 % and 11 % higher total body and right upper extremity lean mass ( all P h and ballers showed enhanced BMC and BMD in the lumbar spine , pelvic region , and lower extremity ( all P greater BMC in the whole body and enhanced BMD in the right upper extremity and femoral neck than the control subjects ( all P total lean mass strongly correlated with total and regional BMC and BMD ( r=0.79 - 0.91 P BMC and BMD variables ( r=0.59 - 0.67 and r=0.60 - 0.70 , respectively ; all P whole-body BMC and BMD ( R=0.93 and R=0.90 , P h and ball participation is associated with improved physical fitness , increased lean and bone masses , and enhanced axial and appendicular BMD in young girls . The combination of anthropometric and fitness-related variables may be used to detect girls with potentially reduced bone mass", "Velez , A , Golem , DL , and Are nt , SM . The impact of a 12-week resistance training program on strength , body composition , and self-concept of Hispanic adolescents . J Strength Cond Res 24(4 ) : 1065 - 1073 , 2010-Current evidence suggests that a resistance training program may be physically and psychologically beneficial for adolescents . The purpose of this study was to examine the effects of a structured resistance training program on strength , body composition , and self-concept in normal and overweight Hispanic adolescents . Male and female participants ( n = 28 ; 16.1 ± 0.2 y ; 164.5 ± 1.4 cm ; 63.3 ± 2.5 kg ; 20.0 ± 1.7 % body fat [ BF ] ) were recruited from a predominantly Hispanic high school . Prior to the 12-week program , strength , body composition , and self-concept were assessed . Subjects were r and omly assigned to a control group ( CON ; n = 15 ) or to a resistance training group ( RT ; n = 13 ) that participated in supervised strength training 3 days/week . All measures were repeated at the end of the 12-week program . RT had significantly greater strength increases for bench press ( p seated row ( p = 0.002 ) , shoulder press ( p and squats ( p = 0.002 ) . RT had significant reductions in % BF ( p = 0.001 ) , whereas CON had slightly increased % BF . RT had an increase in condition/stamina competence ( p = 0.008 ) , attractive body adequacy ( p = 0.017 ) , and global self-worth ( p = 0.013 ) from pretest to posttest , whereas no change was observed for CON . In conclusion , resistance training result ed in significant physiological and psychological improvements in Hispanic adolescents compared to typical school-based activities . These findings indicate that resistance training can be incorporated into the activities of Hispanic adolescents to promote improved health and fitness", "OBJECTIVE To assess different aspects of physical fitness and physical activity in obese and nonobese Flemish youth . RESEARCH METHODS AND PROCEDURES A r and om sample of 3214 Flemish schoolchildren was selected and divided into an \" obese \" and \" nonobese \" group based on body mass index and sum of skinfolds . Physical fitness was assessed by the European physical fitness test battery . Physical activity was estimated by a modified version of the Baecke Question naire . RESULTS Obese subjects had inferior performances on all tests requiring propulsion or lifting of the body mass ( st and ing-broad jump , sit-ups , bent-arm hang , speed shuttle run , and endurance shuttle run ) compared with their nonobese counterparts ( p strength on h and grip ( p leisure-time physical activity ; however , nonobese boys had a higher sport index than their obese counterparts ( p performances on weight-bearing tasks , but did not have lower scores on all fitness components . To encourage adherence to physical activity in obese youth , it is important that activities are tailored to their capabilities . Results suggest that weight-bearing activities should be limited at the start of an intervention with obese participants and alternative activities that rely more on static strength used", "BACKGROUND AND OBJECTIVE Studies on back extensor endurance in adolescents are scarce . This study sought to establish reference data and pattern of back extensor endurance in school-aged adolescents with and without low-back pain ( LBP ) from Nigeria . SUBJECTS AND METHODS This study recruited 625 adolescents aged 11 to 19 years from eight r and omly selected secondary schools . The modified Biering-Sørensen test of Static Muscular Endurance ( BSME ) was used to assess isometric endurance of the back extensors . Demographic and anthropometric data were collected . A modified LBP question naire was used to assess the presence of LBP . Descriptive and inferential analyses were used to analyze data . Significance was set at 0.05 alpha-level . RESULTS The mean isometric holding time ( IHT ) of all the participants was 132.9 $ \\pm$ 65.6 . Males had significantly higher significant ( p=0.026 ) IHT than females . Adolescents without LBP had a higher significant IHT ( p=0.042 ) than those with reported history of previous LBP and those with present LBP ( p=0.000 ) respectively . Using percentile values , poor endurance was defined as IHT that is medium endurance was defined as IHT that ranged between 90 and 193 s and 67 and 170 s for males and females respectively while good endurance was defined as IHT that is > 193 s and > 170 s for males and females respectively . IHT was significantly related to each of body mass index , hip circumference and waist-to-hip ratio ( p Isometric back extensors endurance in Nigerian adolescents was comparable to the original Biering-Sørensen mean value . Majority of the participants had medium endurance performance with the back endurance pattern in the ratio 1:2:1 . Male had higher isometric back extensors endurance than females . Decreased isometric back extensors endurance was associated with the presence of LBP in adolescents", "Background : High-intensity progressive resistance training ( PRT ) improves adiposity and metabolic risk in adults , but has not been investigated in children within a r and omized controlled trial ( RCT ) . Objective : We hypothesized that high-intensity PRT ( 8 weeks , twice a week ) would decrease central adiposity in children , as assessed via waist circumference . Methods Design / Setting / Participants : Concealed r and omization stratified by age and gender was used to allocate rural New Zeal and school students to the wait-list control or PRT group . Intervention : Participants were prescribed two sets ( eight repetitions per set ) of 11 exercises targeting all the major muscle groups at high intensity . Primary Outcome : Waist circumference ; secondary outcomes included whole body fat , muscular fitness ( one repetition maximum ) , cardiorespiratory fitness ( peak oxygen consumption during a treadmill test ) , lipids , insulin sensitivity and fasting glucose . Results : Of the 78 children ( 32 girls and 46 boys ; mean age 12.2(1.3 ) years ) , 51 % were either overweight ( 33 % ) or obese ( 18 % ) . High-intensity PRT significantly improved waist circumference ( mean change PRT −0.8 ( 2.2 ) cm vs + 0.5 ( 1.7 ) cm control ; F=7.59 , P=0.008 ) , fat mass ( mean change PRT + 0.2 ( 1.4 ) kg vs + 1.0 ( 1.2 ) kg control ; F=6.00 , P=0.017 ) , percent body fat ( mean change PRT –0.3 (1.8)% vs + 1.2 (2.1)% control ; F=9.04 , P=0.004 ) , body mass index ( mean change PRT −0.01 ( 0.8 ) kg m−2 vs + 0.4 ( 0.7 ) kg m−2 control ; F=6.02 , P=0.017 ) , upper body strength ( mean change PRT+11.6(6.1 ) kg vs + 2.9(3.7 ) kg control ; F=48.6 , P ( mean change PRT + 42.9(26.6 ) kg vs + 28.5(26.6 ) kg control ; F=4.72 , P=0.034 ) compared to the control group . Waist circumference decreased the most in those with the greatest baseline relative strength ( r=−0.257 , P=0.036 ) , and greatest relative ( r=−0.400 , P=0.001 ) and absolute ( r=0.340 , P=0.006 ) strength gains during the intervention . Conclusion : Isolated high-intensity PRT significantly improves central and whole body adiposity in association with muscle strength in normal-weight and overweight children . The clinical relevance and sustainability of these changes in adiposity should be addressed in future long-term studies", "This study establishes the relationship between the compliance with the governmental physical activity guidelines ( at least a minimum of one hour of moderate to vigorous physical activity , MVPA , five times a week ) , health-related physical fitness and different health related lifestyle variables in a representative sample of Spanish children . Subjects were a representative group of scholars from five schools r and omly selected in Extremadura , a mainly rural region with a very low population density . Statistical analysis comprises a t-test to calculate physical fitness differences between groups , according to the compliance with the mentioned physical activity guidelines . A multinomial logistic regression coefficient is established to determine the differences between the better physical fitness status group (= percentile 75 ) and the poorer physical fitness status group (= percentile 25 ) for each fitness test and gender , body mass index , physical activity , Mediterranean diet index and population size . Main findings show that the compliance with physical activity guidelines result in a better h and grip strength in left h and ( p leg strength ( p speed-agility run ( p 20 m endurance shuttle run ( p lower physical fitness (= percentile 25 ) , whereas there is no relationship between diet quality and subjects ' performance in all physical fitness test evaluated . As a conclusion , this study emphasizes the need to promote an active lifestyle in which physical activity suppose a minimum of one hour of regular MVPA , at least five times a week , to achieve a healthy fitness status", "UNLABELLED This is the first prospect i ve cohort study of the association between bone mass and fracture risk in childhood . A total of 6213 children 9.9 years of age were followed for 24 months . Results showed an 89 % increased risk of fracture per SD decrease in size-adjusted BMC . INTRODUCTION Although previous case-control studies have reported that fracture risk in childhood is inversely related to bone mass , this has not been confirmed in prospect i ve studies . Additionally , it remains unclear which constituent(s ) of bone mass underlie this association . We carried out a prospect i ve cohort study to examine the relationship between DXA measures in children 9.9 years of age and risk of fracture over the following 2 years . MATERIAL S AND METHODS Total body DXA scan results obtained at 9.9 years of age were linked to reported fractures over the following 2 years in children from a large birth cohort in southwest Engl and . DXA measures consisted of total body less head ( TBLH ) BMD , bone area , and BMC , and results of subregional analysis of the humerus . Analyses were adjusted for age , sex , ethnicity , and social position . RESULTS Complete data were available on 6213 children . There was a weak inverse relationship between BMD at 9.9 years and subsequent fracture risk ( OR per SD decrease = 1.12 ; 95 % CI , 1.02 - 1.25 ) . In analyses examining the relationship between fracture risk and volumetric BMD , fracture risk was inversely related to BMC adjusted for bone area , height , and weight ( OR = 1.89 ; 95 % CI , 1.18 - 3.04 ) and to estimated volumetric BMD of the humerus ( OR = 1.29 ; 95 % CI , 1.14 - 1.45 ) . Fracture risk was unrelated to both TBLH and humeral bone area . However , in analyses of the relationship between fracture risk and bone size relative to body size , an inverse association was observed between fracture risk and TBLH area adjusted for height and weight ( OR = 1.51 ; 95 % CI , 1.17 - 1.95 ) . CONCLUSIONS Fracture risk in childhood is related to volumetric BMD , reflecting an influence of determinants of volumetric BMD such as cortical thickness on skeletal fragility . Although bone size per se was not related to fracture risk , we found that children who fracture tend to have a smaller skeleton relative to their overall body size", "Abstract The purpose of the present study was to assess different aspects of physical activity and fitness in order to develop a basis for sport programmes for overweight and obese children . Eighty-eight prepubertal children ( 49 boys , 39 girls , 4.8–11.4 years old , 61 % obese , 14 % overweight and 25 % normal weight ) were examined . Body composition was assessed by combined use of anthropometrics and bioelectrical impedance analysis . Resting energy expenditure ( REE ) and total energy expenditure ( TEE ) were measured by indirect calorimetry ( IC ) and individually calibrated 24-h heart rate ( HR ) monitoring , respectively . Activity-related energy expenditure ( AEE ) and physical activity level ( PAL ) were calculated from TEE and REE . Fitness [ assessed by O2-pulse , respiratory exchange ratio ( RER ) at submaximal work intensities ] was determined by ergometry . The maximal isometric muscle strength of the legs ( m. quadriceps , Fa max , m. ischiocruralis , Fb max ) was measured by computer tensiometry . Children were grouped according to their nutritional state , AEE , O2-pulse and muscle strength . When compared with normal weight children , obese and overweight children had increased fat mass ( FM ) , fat-free mass ( FFM ) , waist-to-hip ratio and REE , but no group differences were observed for TEE , AEE , and PAL . Obese and overweight children spent more hours per day watching TV . After correction for body weight and FFM , no group differences in REE were observed , but normal weight children had a higher O2-pulse than overweight and obese children . By contrast , RER was increased in the latter group . The fittest group had the lowest body weight , BMI , FM and FFM . Children with a low O2-pulse spent more hours per day watching TV . Grouping children according to their degree of muscle strength , younger children ( 4–7.5 years ) did not show group differences in nutritional state , energy expenditure , physical activity and fitness . However , in the group of 7.6- to 11-year-old children , those with the greatest muscle strength and FFM had reduced BMI , skin folds , FM and FFM . FM correlated inversely with O2-pulse , but was not associated with TEE , AEE , PAL or muscle strength . By contrast TV consumption was positively associated with FM . To summarize , overweight and obese children were less fit and watched more TV than their normal weight counterparts . FM did not correspond to TEE , AEE or PAL . Muscle strength was not associated with FM in young children , but was inversely associated with FM in older children . Our cross-sectional data are consistent with the idea that increased fitness and reduced physical inactivity may prevent children from being overweight", "Study Design . This study comprised a cross-sectional part and a prospect i ve part . Objective . To study whether low lumbar extension strength , high lumbar mobility , and high mobility – extension strength ratios are related to current and future low back pain in adolescents . Summary of Background Data . Knowledge is sparse about the significance of lumbar mobility and strength for low back pain in adolescents . Methods . The study population included all the adolescents in the eighth and ninth grade s of a rural municipality ( n = 44 ) and in an urban area ( n = 61 ) during the 1996–1997 school year . At baseline , 88 adolescents ( mean age , 14.7 years ) participated in the study , giving a response rate of 84 % . Low back pain was assessed by question naire as pain or discomfort in the low back during the preceding year . Sagittal lumbar mobility was tested by Schober ’s modified technique , and lumbar strength as static endurance extension strength . The follow-up part was conducted 3 years later , which included 98 % of the adolescents . Results . By bivariate and multivariate analyses in the cross-sectional part of the study , low back pain was found to be highly associated with low lumbar extension strength ( P = 0.004–0.02 ) , and high lumbar mobility – extension strength ratios ( P = 0.005–0.04 ) . Baseline low lumbar extension strength and high lumbar sagittal mobility – extension strength ratios ( P = 0.03 and P = 0.02 , respectively ) predicted low back pain at follow-up assessment in multivariate analyses when control was used for gender , previous low back pain , physical activity , and well-being . No associations were found between plain sagittal mobility and low back pain . Conclusion . The study findings support theories suggesting insufficient strength and stability in the low back as important factors for both concurrent and future low back pain in adolescents", "The study describe changes over 2 years in different physical fitness measures and the relationship between these changes and changes in physical activity . Maximal aerobic work capacity ( Wattmax ) , functional strength , muscle endurance , agility and flexibility were measured in 259 r and omly selected high school boys and girls 16.5 years of age and followed-up 2 years later , while they still attended school . Most physical fitness measures increased over time in boys , and in girls an increase was found in arm extensor strength and trunk extensor endurance , but Wattmax per kg body mass decreased . Changes in physical performance between 16 and 18 years of age seem to be very similar in different countries , despite differences in physical activity patterns and absolute level of performance . No change was found in time of participation in physical activity or sports activity in either gender , but fewer girls participated in leisure-time sports at the 2nd test ( p physical activity or sports activity did not relate to change in physical fitness level . The relationships between level of sports participation ( competition , for health or none ) and physical fitness measures at baseline and at the 2nd test were weak or non-significant . Three explanations for the weak relationship between physical activity and fitness are suggested : ( A ) part of the variability in fitness is explained by genetics , ( B ) growth and hormonal changes , especially in boys , override the stimulus of training , and ( C ) the physical fitness level in adolescents is so high that only physical activity at high relative intensity is supposed to have an effect on the fitness level", "OBJECTIVES We examined the relationship between comprehensive fitness tests and overweight using a school surveillance system in a racially diverse city in the United States . RESEARCH METHODS AND PROCEDURES Trained physical education teachers measured weight , height , and fitness annually from 2001 to 2003 . We compiled data for a cross-sectional analysis ( 11,845 measurements on 6297 students , 5 to 14 years of age ) and a 1-year prospect i ve analysis ( 4215 measurements on 2927 students not overweight at baseline , 5 to 13 years of age ) . Overweight was defined as a BMI > or = 95th percentile ( Centers for Disease Control and Prevention 2000 growth charts ) , and underfit was defined as failing at least one of five fitness tests : endurance run , abdominal strength , flexibility , upper body strength , and agility ( Amateur Athletic Union and Fitnessgram ) . Associations between fitness and overweight were examined using multivariate logistic regression models , adjusting for sociodemographic status and repeated measurements over time . RESULTS The mean number of fitness tests passed was lower among students with a BMI above the 80th percentile . Overweight incidence over 1 year was 7 % and 2 % for underfit and fit girls , respectively ( odds ratio , 3.3 ; 95 % confidence interval , 2.0 to 5.6 ) . Not passing either the endurance run or upper body strength test was associated with overweight incidence in both boys and girls . After adjusting for baseline BMI , the endurance run remained a significant predictor of incident overweight among girls ( odds ratio , 2.0 ; 95 % confidence interval , 1.1 to 3.5 ) . DISCUSSION Findings support a cross-sectional inverse relationship between physical fitness and overweight among school-aged children . The direction of causation between fitness and overweight is not clearly established and merits further study", "Objectives To explore the extent to which muscular strength in adolescence is associated with all cause and cause specific premature mortality ( . Design Prospect i ve cohort study . Setting Sweden . Participants 1 142 599 Swedish male adolescents aged 16 - 19 years were followed over a period of 24 years . Main outcome measures Baseline examinations included knee extension , h and grip , and elbow flexion strength tests , as well as measures of diastolic and systolic blood pressure and body mass index . Cox regression was used to estimate hazard ratios for mortality according to muscular strength categories ( tenths ) . Results During a median follow-up period of 24 years , 26 145 participants died . Suicide was a more frequent cause of death in young adulthood ( 22.3 % ) than was cardiovascular diseases ( 7.8 % ) or cancer ( 14.9 % ) . High muscular strength in adolescence , as assessed by knee extension and h and grip tests , was associated with a 20 - 35 % lower risk of premature mortality due to any cause or cardiovascular disease , independently of body mass index or blood pressure ; no association was observed with mortality due to cancer . Stronger adolescents had a 20 - 30 % lower risk of death from suicide and were 15 - 65 % less likely to have any psychiatric diagnosis ( such as schizophrenia and mood disorders ) . Adolescents in the lowest tenth of muscular strength showed by far the highest risk of mortality for different causes . All cause mortality rates ( per 100 000 person years ) ranged between 122.3 and 86.9 for the weakest and strongest adolescents ; corresponding figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6 and 16.9 for mortality due to suicide . Conclusions Low muscular strength in adolescents is an emerging risk factor for major causes of death in young adulthood , such as suicide and cardiovascular diseases . The effect size observed for all cause mortality was equivalent to that for well established risk factors such as elevated body mass index or blood pressure", "OBJECTIVE To study the effect of a st and ardised training programme focusing on maintenance of fat free mass during weight reduction by energy reduction in obese children . DESIGN R and omised trial of physical training programme and dietary advice ( group A ) versus dietary advice alone ( group B ) . SUBJECTS Thirty obese children and adolescents ( 14 group A , 16 group B ) participated in the 12 week long programme ; 20 children ( 10 group A , 10 group B ) were also reassessed after one year . MEASUREMENTS Fat free mass was estimated from the resistance index , obtained by bioelectrical impedance analysis at baseline , after four , eight , and 12 weeks in all subjects , and after one year in 20 subjects . RESULTS The mean ( SD ) change in fat free mass was significantly different between the two groups after 12 weeks ( group A , 2.68 ( 3.74 ) kg ; group B , 0.43 ( 1.65 ) kg ) . The change in body weight after one year was inversely correlated with the change in fat free mass after 12 weeks ( r = −0.44 ) , as assessed in the 20 subjects . CONCLUSIONS A st and ardised training programme as used in this study can prevent reduction in fat free mass during weight loss in obese children . Reduction in fat free mass during weight reduction might be a risk factor for regain of weight", "This study investigates whether physical activity and physical performance in adolescence are positively related to adult bone mineral density ( BMD ) . In 1974 , physical activity , endurance , and muscular strength were measured in 204 r and omly selected female students , age 16.1 + /- 0.3 year ( range 15 - 17 years ) . Twenty years later , 36 of the women volunteered to undergo a measurement of their BMD . Women who were members in a sports club in adolescence had significantly higher adult BMD ( mean differences of 5 % to 17 % depending on site ) compared with subjects who were not engaged in a sports club . Furthermore , women with persistent weight-bearing activity in adulthood had significantly higher BMD compared with women who had stopped being active or had never been active . The differences ranged between 5 % and 19 % with the highest difference found in trochanter BMD . Stepwise regression analyses showed that membership in a sports club at baseline was a significant independent predictor of BMD in the total body , lumbar spine , legs , trochanter , and femoral neck , explaining 17 - 26 % of the variation in BMD . Change in body weight was a strong independent predictor of BMD of the total body and arms , explaining 8 % of the variation in both sites . In addition , running performance at baseline was an independent predictor of total body BMD , whereas the two-h and lift performance significantly predicted BMD of the total body , legs and trochanter . The hanging leg-lift and h and grip were both significant predictors of arm BMD . In conclusion , membership in a sports club and site-specific physical performance in adolescence together with the change in body weight were significantly associated with adult BMD in premenopausal women", "Study Design . This was a prospect i ve 3-year follow-up study of r and omized matched subgroups of 15-year-old school children with or without low back pain initially . Objective . In addition to low back pain and leisure time physical activity , spinal mobility , trunk muscle strength , and early degenerative findings of the lumbar spine were evaluated . Summary of Background Data . Reliable epidemiologic studies on the prevalence of low back pain and development of early degenerative changes of the lumbar spine in young persons have been sparse . Along with several other characteristics , the relationship of these changes to frequent low back pain in young persons is not known . Methods . After a question naire-based survey was administered , subjects with or without low back pain were examined initially and at follow-up with special reference to leisure time physical activity , anthropometry , spinal mobility , trunk muscle strength , and magnetic resonance imaging findings of the lumbar spine . Results . At baseline and at follow-up , those subjects with initial low back pain were characterized by a low frequency of physical activity and decreased spinal function . During follow-up , the occurrence of disc degeneration increased significantly more in the original group with low back pain than among asymptomatic subjects . Furthermore , disc degeneration at baseline significantly predicted future frequent low back pain . Initial disc protrusion also predicted future frequent low back pain . Conclusion . After the rapid physical growth period , there seemed to be a causal relationship between the early evolution of the degenerative processes of the lower lumbar discs and frequent low back pain in several subjects", "Study Design . A combined cross‐sectional and longitudinal design . Objectives . To investigate relation between , on one h and , self‐reported neck‐shoulder symptoms and , on the other h and , low back symptoms and self‐reported work‐related physical load , psychosocial factors , and individual characteristics and to study the influence of physical capacity in adolescence on neck‐shoulder and low back symptoms in adulthood . Summary of Background Data . Heavy physical work and exposure to vibration constitute risk factors for low back problems , and repetitive and static work are risk factors for neck‐shoulder symptoms in many jobs . The interplay between individual factors and work‐related psychosocial and physical exposure , however , is not well documented . This study addresses effects of adolescent capacity on this interplay in a general population . Methods . A r and om sample of 425 Swedish students was investigated when the students were 16 years and 34 years of age . Sixty‐five percent participated in both examinations ; only those who worked ≥ 6 hours/week at the follow‐up period , 148 men and 90 women , were included in these analyses . Data about musculoskeletal symptoms , work , and sociodemographic and individual characteristics were collected at the age of 34 years ; physical performance data were collected at the ages of 16 years and 34 years . Results . Among the men , self‐employment and worry were associated with neck‐shoulder symptoms ; among the women , monotonous work and high decision latitude were associated with neck‐shoulder symptoms . Low back problems were related to monotonous work among men and women and to exposure to vibration among men . Performance in certain fitness tests at the ages of 16 years and 34 years was negatively associated with musculoskeletal symptoms . Conclusions . The inverse relationships between performance at the age of 16 years and adult musculoskeletal symptoms may imply benefits of early fitness training", "PURPOSE Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children , such as type 2 diabetes . Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults . However , very little is known regarding the effects of exercise on insulin resistance in youth . Therefore , we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes . METHODS Twenty-two overweight Latino adolescent males were r and omly assigned to either a twice-per-week resistance training group ( RT=11 ) or a nonexercising control group ( C=11 ) for 16 wk . Strength was assessed by one-repetition maximum , body composition was quantified by dual-energy x-ray absorptiometry , and insulin sensitivity was determined by the frequently sample d intravenous glucose tolerance test with minimal modeling . RESULTS Significant increases in upper- and lower-body strength were observed in the RT compared with the C group . The RT group significantly increased insulin sensitivity compared with the C group ( P baseline values , insulin sensitivity increased 45.1+/-7.3 % in the RT group versus -0.9+/-12.9 % in controls ( P resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition", " 259 primary school children ( average age 9.2 years ) were r and omly selected from three groups of children whose weights-for-height were 90 - 110 % ( normal 111 ) , > 110 - 120 % ( over weight 25 ) , and > 120 % ( obesity 123 ) of reference values for Bangkok children . They underwent physical fitness tests which included measurement of speed ( 50 meters run ) , flexibility ( sit-reach ) , abdominal strength and endurance ( 30 seconds sit-up ) , vital capacity ( spirometer ) , and indirect maximum oxygen uptake ( VO2 max-submaximal bicycle ergometer ) . The results showed that all physical fitness tests were statistically significantly different ( p sit-up and VO2 max showed statistically significant differences ( p normal weight boys did better than girls ( p flexibility . There were no statistically significant differences between sexes in overweight and obese children . This study demonstrated that physical fitness of obese children was worse than that of normal children in both sexes , especially as measured by 50 meters run , sit-up and VO2 max tests . Thus , promotion of exercise in obese children should be stimulated to develop better physical fitness and weight reduction . In comparison of physical fitness between the sexes , boys had better physical fitness than girls , significant in the normal weight group only . There is no definite explanation as to why increase in weight results in no difference of physical fitness between sexes . Lifestyle , physical skills , and genetic determinants should be considered for interpretation of physical fitness", "OBJECTIVES The mechanical environment is considered to be the most important determinant of bone strength . Local muscle force , in turn , is regarded as the largest source of loading applied to bones . However , the effect of weight-bearing on bone mineral accrual is unclear . Comparing the relationship between muscle force and bone mineral content ( BMC ) in the upper and lower limbs provides a means of investigating this issue . SUBJECTS AND METHODS The study group comprised 258 healthy girls aged 10 - 13 years old at baseline . BMC , lean body mass ( LM ) and fat body mass ( FM ) of total body were assessed by dual-energy X-ray absorptiometry at baseline and 2 years after . The maximal isometric voluntary contraction ( MVC ) of left elbow flexors and knee extensors was evaluated by a dynamometer . A hierarchical linear statistical model with r and om effects was used to analyze the relationship between BMC and limb-matched MVC . Fisher 's z-transformation was used to compare the correlation coefficients between arms and legs . The ratio of BMC to MVC ( BMC /MVC ) in upper and lower limbs was compared using Student 's t-test . RESULTS BMC was highly correlated with MVC in arms and legs ( r(2)=0.54 and 0.50 , respectively ) , and the correlation coefficients did not differ between upper and lower limbs . On the other h and , BMC /MVC was significantly ( 30 % ) higher in leg than in arm . CONCLUSIONS The results indicate that local muscle contraction and weight-bearing exert an additive effect on bone mass accretion in the lower limbs . Exercise regimes combining resistance and impact training should provide larger bone response than either one of them alone in growing children", "The incidence of hip and forearm fracture in elderly men in the United Kingdom is a public health issue , but there is limited knowledge on lifestyle factors affecting male bone health . The aim of this cross-sectional study was to evaluate the relationships between whole body and regional bone mineral status and self-reported participation time in no- , low- , moderate- , and high-impact activities and fitness measurements in 16- to 18-year-old boys . One hundred twenty-eight boys underwent absorptiometry ( DXA ) measurements ( Hologic QDR 1000W ) of bone mineral content ( BMC ) , bone area ( BA ) , and bone mineral density ( BMD ) at the whole body , hip , spine , and forearm . They also completed the EPIC ( European Prospect i ve Investigation of Cancer ) physical activity question naire , which allowed categorization of activities according to impact and aerobic intensity . Fitness and strength were assessed in each subject using estimated VO2 max , grip strength , and back strength . Significant positive relationships were found between BMC , BA , and BMD and the fitness and strength measurements and participation time in high-impact sports at most skeletal sites . The relationships were further examined after adjustment of BMC for height , weight , and bone area , thereby minimizing the influence of body and bone size on these relationships . VO2 max was a significant positive determinant of size-adjusted BMC at the whole body , the ultradistal and one-third radius , and all the hip sites , except the trochanter . Size-adjusted BMC at the forearm sites and trochanter was significantly positively associated with grip strength . Size-adjusted BMC at the whole body and all the hip sites was significantly positively associated with time spent at high-impact activities . Differences in size-adjusted BMC across thirds of time spent at high-impact activities were also examined . Boys in the highest third of high-impact activity had significantly greater size-adjusted whole body BMC and total hip BMC compared to subjects in the lowest third [ + 3.4 (1.2)% for whole body and + 8.5 (2.2)% for hip , both P = 0.001 ] . Boys in the highest third of high-impact activity spent most activity time jogging , playing tennis , football and rugby , basketball , and exercising with weights . Back strength and lean mass were significantly greater in subjects in the highest third compared to those in the middle ( P = 0.02 ) and lowest third ( P = 0.03 ) . No significant differences were found between subjects in each third of high-impact activity for potential confounders including TV viewing , calcium intake , body fat , and height . These findings indicate that participation of male adolescents in a range of high-impact activities for 1 h or more a day is associated with greater bone size and mineral content , especially at the hip", "Objective To examine prospect ively the association between muscular strength and mortality from all causes , cardiovascular disease , and cancer in men . Design Prospect i ve cohort study . Setting Aerobics centre longitudinal study . Participants 8762 men aged 20 - 80 . Main outcome measures All cause mortality up to 31 December 2003 ; muscular strength , quantified by combining one repetition maximal measures for leg and bench presses and further categorised as age specific thirds of the combined strength variable ; and cardiorespiratory fitness assessed by a maximal exercise test on a treadmill . Results During an average follow-up of 18.9 years , 503 deaths occurred ( 145 cardiovascular disease , 199 cancer ) . Age adjusted death rates per 10 000 person years across incremental thirds of muscular strength were 38.9 , 25.9 , and 26.6 for all causes ; 12.1 , 7.6 , and 6.6 for cardiovascular disease ; and 6.1 , 4.9 , and 4.2 for cancer ( all P all cause mortality were 1.0 ( referent ) , 0.72 ( 95 % confidence interval 0.58 to 0.90 ) , and 0.77 ( 0.62 to 0.96 ) ; for death from cardiovascular disease were 1.0 ( referent ) , 0.74 ( 0.50 to 1.10 ) , and 0.71 ( 0.47 to 1.07 ) ; and for death from cancer were 1.0 ( referent ) , 0.72 ( 0.51 to 1.00 ) , and 0.68 ( 0.48 to 0.97 ) . The pattern of the association between muscular strength and death from all causes and cancer persisted after further adjustment for cardiorespiratory fitness ; however , the association between muscular strength and death from cardiovascular disease was attenuated after further adjustment for cardiorespiratory fitness . Conclusion Muscular strength is inversely and independently associated with death from all causes and cancer in men , even after adjusting for cardiorespiratory fitness and other potential confounders" ]	41184226-06ff-11f0-808a-c43d1ab1c353
We summarized 16 controlled studies and evaluated the correlation of resveratrol supplementation with metabolic parameters such as the body weight , waist circumference ( WC ) , systolic blood pressure ( sbp ) , HDL , total cholesterol , triglyceride and glucose levels . This meta- analysis was carried out to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients . PubMed , Scopus , Cochrane and Google Scholar were search ed from inception to December 2018 using relevant keywords . All articles were independently review ed by two authors using predetermined selection criteria . We have selected the studies that investigated the effects of resveratrol on metabolic parameters . Of 16 studies , 10 were performed on human subjects , and in 6 studies animal models were used . St and ard mean difference ( SMD ) with 95 % confidence interval were determined using Der Simonian and Laird r and om-effects modeling , when there was a significant heterogeneity between studies . Funnel plot and Egger ’s test were conducted to examine the risk of publication bias . Pooled effect sizes in human studies indicated a significant impact of resveratrol supplementation on glucose level [ −1.73 ( −2.99 , −0.47 ) ; p = 0.007 ) ] and WC [ −1.73 ( −2.79 , −0.67 ) ; p = 0.001 ] compared with the control group . Also combining the results of studies on rat sample s ( n = 6 ) , indicated significant effect of resveratrol on decreasing weight [ −22.95 ( −44.74 , −1.17 ) ; p = 0.04 ] , TGs [ −6.76 ( −11.10 , −2.42 ) ; p = 0.001 ] , sbp [ −7.30 ( −12.48 , −2.13 ) ; p = 0.006 ] , and it can influence significantly on increasing HDL level ( 4.75 ( 1.87 , 7.63 ) ; p = 0.001 ) . However , resveratrol was not significantly effective on total cholesterol in both sample s. The results of subgroup analysis of human studies showed that resveratrol has significant effect on metabolic parameters ( glucose level and WC ) at the dosage of > 500 mg and with long-term interventions ≥ 10 weeks . Administration of resveratrol can meaningfully reduce the BW , WC , TGs , and glucose level , also it can increase HDL , but not total cholesterol	[ "Background High-fat meals induce postpr and ial inflammation . Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action . There is also an increasing body of evidence supporting the role of curcumin , a polyphenol from the curcuminoid family , as a modulator of proinflammatory processes . Objective The objectives of this study were to investigate the following : 1 ) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal ; and 2 ) the acute combined effects of this combination on the postpr and ial inflammatory response of subjects with abdominal obesity . Methods In a double blind , crossover , r and omized , placebo-controlled study , 11 men and 11 postmenopausal women [ mean ± SD age : 62 ± 5 y ; mean ± SD body mass index ( in kg/m2 ) : 29 ± 3 ] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1 - 2 wk : once after consumption of a dietary supplement ( 200 mg resveratrol and 100 mg curcumin , Res/Cur ) and once after consumption of a placebo ( cellulose ) . Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers , adhesion molecules , and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests . Results Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations . Supplementation with Res/Cur did not modify postpr and ial variations in circulating inflammatory markers ( C-reactive protein , IL-6 , IL-8 , monocyte chemoattractant protein-1 ) and adhesion molecules [ soluble E-selectin , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble intercellular adhesion molecule-1 ] compared to placebo ( PTreatment × Time > 0.05 ) . However , Res/Cur significantly decreased the cumulative postpr and ial response of sVCAM-1 , compared to placebo ( incremental area under the curve -4643 % , P = 0.01 ) . Postpr and ial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments . Conclusions Acute supplementation with Res/Cur has no impact on the postpr and ial inflammation response to a high-fat meal in abdominally obese older adults . Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal . This trial was registered at clinical trials.gov as NCT01964846", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "BACKGROUND AND AIMS Flow-mediated dilatation of the brachial artery ( FMD ) is a biomarker of endothelial function and cardiovascular health . Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity . Various food ingredients such as polyphenols have been shown to improve FMD . We investigated whether consuming resveratrol , a polyphenol found in red wine , can enhance FMD acutely and whether there is a dose-response relationship for this effect . METHODS AND RESULTS 19 overweight/obese ( BMI 25 - 35 kg m(-2 ) ) men or post-menopausal women with untreated borderline hypertension ( systolic BP : 130 - 160 mmHg or diastolic BP : 85 - 100 mmHg ) consumed three doses of resveratrol ( resVida ™ 30 , 90 and 270 mg ) and a placebo at weekly intervals in a double-blind , r and omized crossover comparison . One hour after consumption of the supplement , plasma resveratrol and FMD were measured . Data were analyzed by linear regression versus log(10 ) dose of resveratrol . 14 men and 5 women ( age 55 ± 2 years , BMI 28.7 ± 0.5 kg m(-2 ) , BP 141 ± 2/89 ± 1 mmHg ) completed this study . There was a significant dose effect of resveratrol on plasma resveratrol concentration ( P on FMD ( P ( placebo ) to 7.7 ± 1.5 % after 270 mg resveratrol . FMD was also linearly related to log(10 ) plasma resveratrol concentration ( P Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner . This effect may contribute to the purported cardiovascular health benefits of grapes and red wine", "BACKGROUND & AIMS Nonalcoholic fatty liver disease ( NAFLD ) , characterized by accumulation of hepatic triglycerides ( steatosis ) , is associated with abdominal obesity , insulin resistance , and inflammation . Although weight loss via calorie restriction reduces features of NAFLD , there is no pharmacologic therapy . Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism . We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD . METHODS Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane , Australia from 2011 through 2012 . They were r and omly assigned to groups given 3000 mg resveratrol ( n = 10 ) or placebo ( n = 10 ) daily for 8 weeks . Outcomes included insulin resistance ( assessed by the euglycemic-hyperinsulinemic clamp ) , hepatic steatosis , and abdominal fat distribution ( assessed by magnetic resonance spectroscopy and imaging ) . Plasma markers of inflammation , as well as metabolic , hepatic , and antioxidant function , were measured ; transcription of target genes was measured in peripheral blood mononuclear cells . Resveratrol pharmacokinetics and safety were assessed . RESULTS Eight-week administration of resveratrol did not reduce insulin resistance , steatosis , or abdominal fat distribution when compared with baseline . No change was observed in plasma lipids or antioxidant activity . Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group . Resveratrol did not significantly alter transcription of NQO1 , PTP1B , IL6 , or HO1 in peripheral blood mononuclear cells . Resveratrol was well-tolerated . CONCLUSIONS Eight weeks administration of resveratrol did not significantly improve any features of NAFLD , compared with placebo , but it increased hepatic stress , based on observed increases in levels of liver enzymes . Further studies are needed to determine whether agents that are purported to mimic calorie restriction , such as resveratrol , are safe and effective for complications of obesity . Clinical trials registration no : ACTRN12612001135808", "OBJECTIVE To evaluate the efficacy of an orlistat-resveratrol ( O-R ) combination in subjects with obesity over a 6-month period . METHODS This study was a double-blind , parallel , r and omized controlled clinical trial . Patients fulfilling the selection criteria ( age from 20 to 60 years and body mass index ( BMI ) ≥30 and ≤39.9 kg/m(2 ) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks . Then the participants were r and omly assigned to four groups , placebo , resveratrol , orlistat , or O-R , and they consumed the energy-reduced diet for 6 months . The study consisted of seven visits . During each visit , a 24-h recall was performed , along with measurements of anthropometric and serum biochemical parameters . RESULTS A total of 161 participants were selected . Of these , 84 participants completed the study . A significant weight loss of -6.82 kg ( 95 % CI -8.37 to -5.26 ) was observed in the O-R group compared with -3.50 kg ( -5.05 to -1.95 , P = 0.021 ) in the placebo group . In contrast , the -6.02 kg ( -7.68 to -4.36 ) orlistat and -4.68 kg ( -6.64 to -2.71 ) resveratrol monotherapy losses did not significantly differ from the placebo . Significant decreases in BMI , waist circumference , fat mass , triglycerides , leptin , and leptin/adiponectin ratio were observed with the O-R combination . CONCLUSIONS The O-R combination was the most effective weight loss treatment", "Polyphenolic compounds , such as resveratrol , have recently received widespread interest because of their ability to mimic effects of calorie restriction . The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology and underlying processes . Eleven healthy obese men were supplemented with placebo and resveratrol for 30 days ( 150 mg per day ) , separated by a 4-week washout period in a double-blind r and omized crossover design . A postpr and ial abdominal subcutaneous adipose tissue biopsy was collected to assess adipose tissue morphology and gene expression using microarray analysis . Resveratrol significantly decreased adipocyte size , with a shift toward a reduction in the proportion of large and very-large adipocytes and an increase in small adipocytes . Microarray analysis revealed downregulation of Wnt and Notch signaling pathways and upregulation of pathways involved in cell cycle regulation after resveratrol supplementation , suggesting enhanced adipogenesis . Furthermore , lysosomal/phagosomal pathway and transcription factor EB were upregulated reflecting an alternative pathway of lipid breakdown by autophagy . Further research is necessary to investigate whether resveratrol improves adipose tissue function" ]	411842a8-06ff-11f0-808a-c43d1ab1c353
CONTEXT Uncontrolled hypertension remains a widely prevalent cardiovascular risk factor in the U.S. team-based care , established by adding new staff or changing the roles of existing staff such as nurses and pharmacists to work with a primary care provider and the patient . Team-based care has the potential to improve the quality of hypertension management . The goal of this Community Guide systematic review was to examine the effectiveness of team-based care in improving blood pressure ( BP ) outcomes . EVIDENCE ACQUISITION An existing systematic review ( search period , January 1980-July 2003 ) assessing team-based care for BP control was supplemented with a Community Guide up date ( January 2003-May 2012 ) . For the Community Guide up date , two review ers independently abstract ed data and assessed quality of eligible studies . EVIDENCE SYNTHESIS Twenty-eight studies in the prior review ( 1980 - 2003 ) and an additional 52 studies from the Community Guide up date ( 2003 - 2012 ) qualified for inclusion . Results from both bodies of evidence suggest that team-based care is effective in improving BP outcomes . From the up date , the proportion of patients with controlled BP improved ( median increase=12 percentage points ) ; systolic BP decreased ( median reduction=5.4 mmHg ) ; and diastolic BP also decreased ( median reduction=1.8 mmHg ) . CONCLUSIONS Team-based care increased the proportion of people with controlled BP and reduced both systolic and diastolic BP , especially when pharmacists and nurses were part of the team . Findings are applicable to a range of U.S. setting s and population groups . Implementation of this multidisciplinary approach will require health system-level organizational changes and could be an important element of the medical home	[ "BACKGROUND African American men with hypertension in low socioeconomic urban population s achieve poor rates of hypertension control and suffer early from its complications . METHODS In a r and omized clinical trial with 309 hypertensive urban African American men aged 21 to 54 years , we evaluated the effectiveness of a more intensive comprehensive educational-behavioral-pharmacologic intervention by a nurse practitioner-community health worker-physician ( NP/CHW/MD ) team and a less intensive education and referral intervention in controlling blood pressure ( BP ) and minimizing progression of left ventricular hypertrophy ( LVH ) and renal insufficiency . Changes in BP , left ventricular mass ( LVM ) , and serum creatinine from baseline to 36 months were compared between groups . RESULTS At 36 months , the mean systolic BP/diastolic BP change from baseline was -7.5/-10.1 mm Hg for the more intensive group and + 3.4/-3.7 mm Hg for the less intensive group ( P = .001 and .005 for between-group differences in systolic BP and diastolic BP , respectively ) . The proportion of men with controlled BP ( LVM was significantly lower in the more intensive group than in the less intensive group ( more intensive , 274 g ; less intensive , 311 g ; P = .004 ) . There was a trend toward slowing of the progression of renal insufficiency ( incidence of 50 % increase in serum creatinine ) in the more intensive group compared to the less intensive group ( more intensive , 5.2 % ; less intensive , 8.0 % ; P = .08 ) . CONCLUSIONS During 36 months , the more intensive intervention led to a lower BP and decreased progression of LVH in a sample of hypertensive young African American men", "Background —Hypertension is a leading mortality risk factor yet inadequately controlled in most affected subjects . Effective programs to address this problem are lacking . We hypothesized that an information technology – supported management program could help improve blood pressure ( BP ) control . Methods and Results —This r and omized controlled trial included 223 primary care hypertensive subjects with mean 24-hour BP > 130/80 and daytime BP > 135/85 mm Hg measured with ambulatory monitoring ( ABPM ) . Intervention subjects received a BP monitor and access to an information technology – supported adherence and BP monitoring system providing nurses , pharmacists , and physicians with monthly reports . Control subjects received usual care . The mean ( ±SD ) follow-up was 348 ( ±78 ) and 349 ( ±84 ) days in the intervention and control group , respectively . The primary end point of the change in the mean 24-hour ambulatory BP was consistently greater in intervention subjects for both systolic ( −11.9 versus −7.1 mm Hg ; P ) and diastolic BP ( −6.6 versus −4.5 mm Hg ; P=0.007 ) . The proportion of subjects that achieved Canadian Guideline target BP ( 46.0 % versus 28.6 % ) was also greater in the intervention group ( P=0.006 ) . We observed similar BP declines for ABPM and self-recorded home BP suggesting the latter could be an alternative for confirming BP control . The intervention was associated with more physician-driven antihypertensive dose adjustments or changes in agents ( P=0.03 ) , more antihypertensive classes at study end ( P=0.007 ) , and a trend toward improved adherence measured by prescription refills ( P=0.07 ) . Conclusions —This multidisciplinary information technology – supported program that provided feedback to patients and healthcare providers significantly improved blood pressure levels in a primary care setting", "OBJECTIVE : To evaluate the effectiveness of a community pharmacist-based home blood pressure ( BP ) monitoring program . DESIGN : Trial of a high-intensity ( HI ) versus low-intensity ( LI ) intervention r and omized in 12 community pharmacies . The HI intervention comprised 4 face-to-face visits with a trained pharmacist . Pharmacists provided patient-specific education about hypertension . Following the first and third visits , patients were provided with a home BP monitoring device and instructed to measure their BP at least once daily for the next month . Home BP readings were used by the pharmacists to develop treatment recommendations for the patient ’s physician . Recommendations were discussed with the physician and , if approved , implemented by the pharmacist . In the LI intervention , pharmacists measured patients BP in the pharmacy and referred them to their physician for evaluation . PARTICIPANTS : Patients with uncontrolled BP at baseline . MEASUREMENTS : The main outcomes were the differences in systolic and diastolic BP ( SBP and DBP ) from baseline to follow-up between the HI and LI patients . RESULTS : The study enrolled 125 patients , 64 in the HI and 61 in the LI group . From baseline , SBP declined 13.4 mmHg in the HI group and 9.0 mmHg in the LI group . At the final visit , the difference in SBP/DBP change between the HI and LI group was −4.5/−3.2 mmHg ( P=.12 for SBP and P=.03 for DBP ) . CONCLUSIONS : The HI intervention achieved a lower DBP and this model could be a strategy for patients with hypertension", "The effect of pharmaceutical care on the prevention , detection , and resolution of medication-related problems in high-risk patients in a rural community was studied . Adult patients who received care at clinics in a medically underserved area of Alabama and who were identified as being at high risk of medication-related adverse events were r and omly assigned to a control group or an intervention group . The control group received st and ard medical care , and the intervention group received pharmaceutical care , including a medical record review , a medication history review , pharmacotherapeutic evaluation , and patient medication education and monitoring over a one-year period . A total of 69 patients completed the study ( 33 in the intervention group and 36 in the control group ) . The percentage of patients responding to hypertension , diabetes , dyslipidemia , and anticoagulation therapy increased significantly in the intervention group and declined in the control group . Ratings for inappropriate prescribing improved in all 10 domains evaluated in the intervention group but worsened in 5 domains in the control group . There were no significant differences between the groups at 12 months in health-related quality of life or medication misadventures . Medication compliance scores improved in the intervention group but not in the control group . Medication knowledge increased in the intervention group and decreased in the control group . Pharmaceutical care in a rural , community-based setting appeared to reduce inappropriate prescribing , enhance disease management , and improve medication compliance and knowledge without adversely affecting health-related quality of life", "Background We examined the effectiveness of a structured collaboration in general practice between a practice nurse , a peer health educator , the general practitioner ( GP ) and a GP assistant in providing intensified preventive care for patients at high risk of developing cardiovascular diseases . Design A r and omized controlled trial in three healthcare centres ( 18 GPs ) in deprived neighbourhoods of two major Dutch cities . Methods Two hundred seventy-five high-risk patients ( 30 - 70 years ) from various ethnic groups were r and omized to intervention ( n = 137 ) or usual care group ( n = 138 ) . We determined group differences in outcomes [ 10-year absolute risk ( Framingham risk equation ) , blood pressure , lipids and body mass index ] at 12-month follow-up . Results The 10-year absolute risk was reduced by 1.76 % ( st and ard error : 0.81 ) in intervention and by 2.27 % ( st and ard error : 0.69 ) in usual care group ; the difference in mean change was 0.88 % [ 95 % confidence interval : −1.16 to 2.93 ] . In both groups significant reductions were observed in the following individual risk factors : total cholesterol , total cholesterol/high-density lipoprotein cholesterol , and low-density lipoprotein cholesterol , with no relevance between group differences . Conclusion The cardiovascular risk profile of intervention and control patients improved after 1-year follow-up . However , no extra effect of the structured preventive care on the risk for cardiovascular diseases was achieved . Eur J Cardiovasc Prev Rehabil 15:488 - 493 © 2008 The European Society of", "Background Blood pressure ( BP ) control remains elusive for many Americans . Although home health nurses are uniquely positioned to help vulnerable individuals achieve BP control , hypertension ( HTN ) management has not been a high priority in post-acute care . Objective To examine the effects of two home-based interventions design ed to improve BP outcomes among high-risk African-American patients . Design Cluster r and omized controlled trial . Participants A total of 845 newly admitted patients with uncontrolled HTN ( JNC7 stages 1 or 2 ) . Interventions The “ basic ” intervention delivered key HTN information to clinicians and patients , and a home BP monitor to patients , while the patients received usual post-acute care . The “ augmented ” intervention provided more intensive and extensive HTN information , monitoring and feedback for 3 months beyond the index home care admission . Measures Primary : BP control . Secondary : reductions in mmHG SBP and DBP , improvements in proportions improving JNC7 stage or achieving clinical ly meaningful reductions in SBP and DBP . Methods Multivariate regression models . Key Results The basic intervention produced no significant BP improvements ; the augmented intervention significantly improved stage 2 patients ’ outcomes . Among stage 2 patients , the augmented intervention increased BP control by 8.7 percentage points relative to usual care ( 8.9 % vs. 17.6 % ; p = 0.01 ) , yielded an 8.3 mmHG relative reduction in SBP ( p = 0.01 ) , and increased the proportion achieving at least a 20 mmHG reduction in SBP by 16.4 percentage points ( p = 0.01 ) . Conclusion Among stage 2 patients , a nurse-led intervention providing additional HTN medication review and patient self-management support during the 3-month post-acute care period yielded significant improvements in 3-month BP control , plus improvements in secondary BP outcomes", "Background Case management has emerged as a promising alternative approach to supplement traditional one-on-one sessions between patients and doctors for improving the quality of care in chronic diseases such as coronary heart disease ( CHD ) . However , data are lacking in terms of its efficacy and cost-effectiveness when implemented in ethnic and low-income population s. Methods The Stanford and San Mateo Heart to Heart ( HTH ) project is a r and omized controlled clinical trial design ed to rigorously evaluate the efficacy and cost-effectiveness of a multi-risk cardiovascular case management program in low-income , primarily ethnic minority patients served by a local county health care system in California . R and omization occurred at the patient level . The primary outcome measure is the absolute CHD risk over 10 years . Secondary outcome measures include adherence to guidelines on CHD prevention practice . We documented the study design , methodology , and baseline sociodemographic , clinical and lifestyle characteristics of 419 participants . Results We achieved equal distributions of the sociodemographic , biophysical and lifestyle characteristics between the two r and omization groups . HTH participants had a mean age of 56 years , 63 % were Latinos/Hispanics , 65 % female , 61 % less educated , and 62 % were not employed . Twenty percent of participants reported having a prior cardiovascular event . 10-year CHD risk averaged 18 % in men and 13 % in women despite a modest low-density lipoprotein cholesterol level and a high on-treatment percentage at baseline . Sixty-three percent of participants were diagnosed with diabetes and an additional 22 % had metabolic syndrome . In addition , many participants had depressed high-density lipoprotein ( HDL ) cholesterol levels and elevated values of total cholesterol-to-HDL ratio , triglycerides , triglyceride-to-HDL ratio , and blood pressure . Furthermore , nearly 70 % of participants were obese , 45 % had a family history of CHD or stroke , and 16 % were current smokers . Conclusion We have recruited an ethnically diverse , low-income cohort in which to implement a case management approach and test its efficacy and cost-effectiveness . HTH will advance the scientific underst and ing of better strategies for CHD prevention among these priority sub population s and aid in guiding future practice that will reduce health disparities", "Background and Objectives : Older adults ' adherence to antihypertensive medications is far lower than what is considered necessary for clinical effectiveness , despite the risks for adverse cardiovascular events from uncontrolled blood pressure ( BP ) in the elderly . This pilot study tested a novel 8-week behavioral feedback intervention to improve antihypertensive medication adherence ( MA ) and BP control among older adults on existing treatment for hypertension . Methods : Adults 60 years old , or older taking at least 1 antihypertensive medication were r and omized to receive the nurse-delivered adherence intervention or usual care . Medication adherence was monitored continuously using electronic monitoring for 20 weeks . Intervention-group participants received biweekly MA and BP feedback , habit counseling , medication and disease education , a medication instruction card , and were given an electronic medication bottle cap with a digital display that provided daily adherence feedback during the 8-week intervention . Blood pressure was measured by a nurse at 12 and 20 weeks after r and omization . Adherence and BP outcomes were described using descriptive statistics and analyzed for between- and within-group differences using Mann-Whitney U tests . Results : Fifteen participants ( median age , 71 years ; 73 % female ) were eligible for r and omization . Participants took an average of 5.8 prescription medications and 2.93 over-the-counter medications per day . A nonsignificant difference was noted in baseline MA between groups . At the end of the intervention , the treatment group had better antihypertensive MA than did the control group ( median MA : 100 % vs 27.3 % , U = 5.00 , P = .013 ) . Systolic BP improved slightly in the intervention group during the study and was significantly different at week 12 ( median systolic BP : 130 vs 152 mm Hg ; U = 4.50 , P = .008 ) . Diastolic BP was largely unchanged over the course of the study . Conclusion : The results indicate that the intervention had a positive effect on MA . Additional testing is needed to further evaluate the intervention and its effect on adherence behavior and BP control", "BACKGROUND St and ard office-based approaches to controlling hypertension show limited success . Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent , regular blood pressure ( BP ) monitoring . We tested the efficacy of a physician-directed , nurse-managed , home-based system for hypertension management with st and ardized algorithms to modulate drug therapy , based on patients ' reports of home BP . METHODS We r and omized out patients requiring drug therapy for hypertension according to the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) criteria to receive usual medical care only ( UC , n = 76 ) or usual care plus nurse care management intervention ( INT , n = 74 ) over a 6-month period . RESULTS Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC : 14.2 + /- 18.1 versus 5.7 + /- 18.7 mm Hg systolic ( P or more changes in drug therapy in 97 % of INT patients versus 43 % of UC patients , and 70 % of INT patients received two or more drugs versus 46 % of UC . Average daily adherence to medication , measured by electronic drug event monitors , was superior among INT subjects ( mean + /- SD , 80.5 % + /- 23.0 % ) than among UC subjects ( 69.2 + /- 31.1 % ; t(113 ) = 2.199 , P = .03 ) . There were no significant adverse drug reactions in either group . CONCLUSIONS Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension", "This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer", "OBJECTIVE To evaluate the effect of a 9-month community pharmacy-based medication therapy management ( MTM ) program on quality of care in patients with diabetes and hypertension . DESIGN R and omized controlled trial . SETTING Tulsa , OK , between November 2005 and July 2007 . PATIENTS 52 patients with diabetes and hypertension who were enrolled in a managed care organization . INTERVENTION During monthly visits , intervention group participants received MTM services for hypertension and diabetes management . MAIN OUTCOME MEASURES Systolic blood pressure ( SBP ) , percentage at goal blood pressure ( , and antihypertensive medication adherence . RESULTS The mean intervention group SBP decreased 17.32 mm Hg , whereas the mean control group SBP level increased 2.73 mm Hg ( P = 0.003 ) . The percentage of patients at goal blood pressure increased from 16.0 % to 48.0 % in the intervention group and decreased from 20.0 % to 6.67 % in the control group . Intervention group participants were 12.92 times more likely than control group participants to achieve goal blood pressure ( P = 0.021 ) . Although the mean adherence rate in the intervention group increased 7.0 % while remaining fairly constant in the control group ( -0.7 % ) , this group difference was not statistically significant . CONCLUSION A community pharmacy-based hypertension MTM program was effective in improving blood pressure control among managed care enrollees with diabetes and hypertension . Community pharmacists are strategically positioned to provide MTM services and effectively communicate with providers to improve quality of care for patients", "Hypertension is a major risk factor for developing cardiovascular disease and is more prevalent in African Americans compared with Caucasians . African Americans are often underrepresented in clinical trials . This study was composed of a largely urban African American cohort of hypertensive patients . This was a prospect i ve , 4-arm , r and omized controlled trial design ed to evaluate the comparative effectiveness of both physician and patient education ( PPE ) , patient education only ( PAE ) , and physician education only ( PHE ) vs usual care ( UC ) . Hypertension specialists gave a series of didactic lectures to the physicians , while a nurse educator performed the patient education . The mean adjusted difference in systolic blood pressure ( SBP ) from baseline in the PPE group was an average reduction of 12 mm Hg ( 95 % confidence interval [ CI ] , -4.5 to -19.4 ) at 6-months , followed by average reductions of 4.6 mm Hg ( 6.9 to -16.12 ) in the PAE group , 4.1 mm Hg ( 3.4 to -11.7 ) in the PHE group , and 2.6 mm Hg ( 3 to -8.2 ) in the UC group . The PPE group achieved a significantly better reduction in SBP compared with the UC group . Additional research should be conducted to evaluate whether the use of certified hypertension educators in collaboration with physicians will result in a similar blood pressure reduction", "African Americans have a higher prevalence of hypertension and poorer cardiovascular and renal outcomes than white Americans . The objective of this study was to determine whether a telephonic nurse disease management ( DM ) program design ed for African Americans is more effective than a home monitoring program alone to increase blood pressure ( BP ) control among African Americans enrolled in a national health plan . A prospect i ve r and omized controlled study ( March 2006-December 2007 ) was conducted , with 12 months of follow-up on each subject . A total of 5932 health plan members were r and omly selected from the population of self-identified African Americans , age 23 and older , in health maintenance organization plans , with hypertension ; 954 accepted , 638 completed initial assessment , and 485 completed follow-up assessment . The intervention consisted of telephonic nurse DM ( intervention group ) including educational material s , lifestyle and diet counseling , and home BP monitor vs. home BP monitor alone ( control group ) . Measurements included proportion with BP Results revealed that systolic BP was lower in the intervention group ( adjusted means 123.6 vs. 126.7 mm Hg , P = 0.03 ) ; there was no difference for diastolic BP . The intervention group was 50 % more likely to have BP in control ( odds ratio [ OR ] = 1.50 , 95 % confidence interval [ CI ] 0.997 - 2.27 , P = 0.052 ) and 46 % more likely to monitor BP at least weekly ( OR 1.46 , 95 % CI 1.07 - 2.00 , P = 0.02 ) than the control group . A nurse DM program tailored for African Americans was effective at decreasing systolic BP and increasing the frequency of self-monitoring of BP to a greater extent than home monitoring alone . Recruitment and program completion rates could be improved for maximal impact", "Purpose To assess whether VA MEDIC-E ( Veterans Affairs Multi-disciplinary Education and Diabetes Intervention for Cardiac risk reduction[EM DASH ] Extended for 6 months ) , a pharmacist-led shared medical appointments program , could improve attainment of target goals for hypertension , hyperglycemia , hyperlipidemia , and tobacco use in patients with type 2 diabetes compared to st and ard primary care after 6 months of intervention . Methods A r and omized , controlled trial of VA MEDIC-E ( n = 50 ) versus st and ard primary care ( n = 49 ) in veterans with type 2 diabetes , hemoglobin A1c ( A1C ) > 7 % , blood pressure ( BP ) > 130/80 mmHg , and low density lipoprotein cholesterol ( LDL-C ) > 100mg/dl ( 2.59 mmol/l ) in the previous 6 months was conducted . The VA MEDIC-E intervention consisted of 4 weekly group sessions followed by 5 monthly booster group sessions . Each 2-hour session included 1 hour of multidisciplinary diabetes specific healthy lifestyle education and 1 hour of pharmacotherapeutic interventions performed by a clinical pharmacist . Evaluation measures included lab values of A1C , LDL cholesterol , BP , and goal attainment of these values , and diabetes self-care behavior question naires at 6 months . Results The r and omization groups were similar at baseline in all cardiovascular risk factors except for LDL , which was significantly lower in the MEDIC-E arm . At 6 months , significant improvements from baseline were found in the intervention arm for exercise , foot care , and goal attainment of A1C , LDL-C , and BP but not in the control arm . Conclusions The results of this study demonstrate that the pharmacist-led group intervention program for 6 months was an efficacious and sustainable collaborative care approach to managing diabetes and reducing associated cardiovascular risk", "CONTEXT Poor medication adherence diminishes the health benefits of pharmacotherapies . Elderly patients with coronary risk factors frequently require treatment with multiple medications , placing them at increased risk for nonadherence . OBJECTIVE To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PATIENTS A multiphase , prospect i ve study with an observational phase and a r and omized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications . The study was conducted from June 2004 to August 2006 . INTERVENTION After a 2-month run-in phase ( measurement of baseline adherence , BP , and LDL-C ) , patients entered a 6-month intervention phase ( st and ardized medication education , regular follow-up by pharmacists , and medications dispensed in time-specific packs ) . Following the intervention phase , patients were r and omized to continued pharmacy care vs usual care for an additional 6 months . MAIN OUTCOME MEASURES Primary end point of the observation phase was change in the proportion of pills taken vs baseline ; secondary end points were the associated changes in BP and LDL-C. Primary end point of the r and omization phase was the between-group comparison of medication persistence . RESULTS A total of 200 elderly patients ( 77.1 % men ; mean [ SD ] age , 78 [ 8.3 ] years ) , taking a mean ( SD ) of 9 ( 3 ) chronic medications were enrolled . Coronary risk factors included drug-treated hypertension in 184 patients ( 91.5 % ) and drug-treated hyperlipidemia in 162 ( 80.6 % ) . Mean ( SD ) baseline medication adherence was 61.2 % ( 13.5 % ) . After 6 months of intervention , medication adherence increased to 96.9 % ( 5.2 % ; P systolic BP ( 133.2 [ 14.9 ] to 129.9 [ 16.0 ] mm Hg ; P = .02 ) and LDL-C ( 91.7 [ 26.1 ] to 86.8 [ 23.4 ] mg/dL ; P = .001 ) . Six months after r and omization , the persistence of medication adherence decreased to 69.1 % ( 16.4 % ) among those patients assigned to usual care , whereas it was sustained at 95.5 % ( 7.7 % ) in pharmacy care ( P reductions in systolic BP in the pharmacy care group ( -6.9 mm Hg ; 95 % CI , -10.7 to -3.1 mm Hg ) vs the usual care group ( -1.0 mm Hg ; 95 % CI , -5.9 to 3.9 mm Hg ; P = .04 ) , but no significant between-group differences in LDL-C levels or reductions . CONCLUSIONS A pharmacy care program led to increases in medication adherence , medication persistence , and clinical ly meaningful reductions in BP , whereas discontinuation of the program was associated with decreased medication adherence and persistence . TRIAL REGISTRATION clinical trials.gov Identifier :", "Background Patient-shared electronic health records provide opportunities for care outside of office visits . However , those who might benefit may be unable to or choose not to use these re sources , while others might not need them . Objective Electronic Communications and Home Blood Pressure Monitoring ( e-BP ) was a r and omized trial that demonstrated that Web-based pharmacist care led to improved blood pressure ( BP ) control . During recruitment we attempted to contact all patients with hypertension from 10 clinics to determine whether they were eligible and willing to participate . We wanted to know whether particular subgroups , particularly those from vulnerable population s , were less willing to participate or unable to because they lacked computer access . Methods From 2005 to 2006 , we sent invitation letters to and attempted to recruit 9298 patients with hypertension . Eligibility to participate in the trial included access to a computer and the Internet , an email address , and uncontrolled BP ( BP ≥ 140/90 mmHg ) . Generalized linear models within a modified Poisson regression framework were used to estimate the relative risk ( RR ) of in eligibility due to lack of computer access and of having uncontrolled BP . Results We were able to contact 95.1 % ( 8840/9298 ) of patients . Those refusing participation ( 3032/8840 , 34.3 % ) were significantly more likely ( P Medicaid insurance . Among patients who answered survey questions , 22.8 % ( 1673/7354 ) did not have computer access . Older age , minority race , and lower levels of education were risk factors for lack of computer access , with education as the strongest predictor ( RR 2.63 , 95 % CI 2.30 - 3.01 for those with a high school degree compared to a college education ) . Among hypertensive patients with computer access who were willing to participate , African American race ( RR 1.22 , 95 % CI 1.06 - 1.40 ) , male sex ( RR 1.28 , 95 % CI 1.18 - 1.38 ) , and obesity ( RR 1.53 , 95 % CI 1.31 - 1.79 ) were risk factors for uncontrolled BP . Conclusion Older age , lower socioeconomic status , and lower levels of education were associated with decreased access to and willingness to participate in a Web-based intervention to improve hypertension control . Failure to ameliorate this may worsen health care disparities . Trial Registration Clinical trials.gov NCT00158639 ; http://www . clinical trials.gov/ct2/show/NCT00158639 ( Archived by WebCite at http://www.webcitation.org/5v1jnHaeo", "BACKGROUND Patients with depression and poorly controlled diabetes , coronary heart disease , or both have an increased risk of adverse outcomes and high health care costs . We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients . METHODS We conducted a single-blind , r and omized , controlled trial in 14 primary care clinics in an integrated health care system in Washington State , involving 214 participants with poorly controlled diabetes , coronary heart disease , or both and coexisting depression . Patients were r and omly assigned to the usual-care group or to the intervention group , in which a medically supervised nurse , working with each patient 's primary care physician , provided guideline -based , collaborative care management , with the goal of controlling risk factors associated with multiple diseases . The primary outcome was based on simultaneous modeling of glycated hemoglobin , low-density lipoprotein ( LDL ) cholesterol , and systolic blood-pressure levels and Symptom Checklist-20 ( SCL-20 ) depression outcomes at 12 months ; this modeling allowed estimation of a single overall treatment effect . RESULTS As compared with controls , patients in the intervention group had greater overall 12-month improvement across glycated hemoglobin levels ( difference , 0.58 % ) , LDL cholesterol levels ( difference , 6.9 mg per deciliter [ 0.2 mmol per liter ] ) , systolic blood pressure ( difference , 5.1 mm Hg ) , and SCL-20 depression scores ( difference , 0.40 points ) ( P adjustments of insulin ( P=0.006 ) , antihypertensive medications ( P antidepressant medications ( P better quality of life ( P greater satisfaction with care for diabetes , coronary heart disease , or both ( P with care for depression ( P usual care , an intervention involving nurses who provided guideline -based , patient-centered management of depression and chronic disease significantly improved control of medical disease and depression . ( Funded by the National Institute of Mental Health ; Clinical Trials.gov number , NCT00468676 . )", "BACKGROUND Studies have demonstrated that blood pressure ( BP ) control can be improved when clinical pharmacists assist with patient management . The objective of this study was to evaluate if a physician and pharmacist collaborative model in community-based medical offices could improve BP control . METHODS This was a prospect i ve , cluster r and omized , controlled clinical trial with clinics r and omized to a control group ( n = 3 ) or to an intervention group ( n = 3 ) . The study enrolled 402 patients ( mean age , 58.3 years ) with uncontrolled hypertension . Clinical pharmacists made drug therapy recommendations to physicians based on national guidelines . Research nurses performed BP measurements and 24-hour BP monitoring . RESULTS The mean ( SD ) guideline adherence scores increased from 49.4 ( 19.3 ) at baseline to 53.4 ( 18.1 ) at 6 months ( 8.1 % increase ) in the control group and from 40.4 ( 22.6 ) at baseline to 62.8 ( 13.5 ) at 6 months ( 55.4 % increase ) in the intervention group ( P = .09 for adjusted between-group comparison ) . The mean BP decreased 6.8/4.5 mm Hg in the control group and 20.7/9.7 mm Hg in the intervention group ( P systolic BP was -12.0 ( 95 % confidence interval [ CI ] , -24.0 to 0.0 ) mm Hg , while the adjusted difference in diastolic BP was -1.8 ( 95 % CI , -11.9 to 8.3 ) mm Hg . The 24-hour BP levels showed similar effect sizes . Blood pressure was controlled in 29.9 % of patients in the control group and in 63.9 % of patients in the intervention group ( adjusted odds ratio , 3.2 ; 95 % CI , 2.0 - 5.1 ; P A physician and pharmacist collaborative intervention achieved significantly better mean BP and overall BP control rates compared with a control group . Additional research should be conducted to evaluate efficient strategies to implement team-based chronic disease management . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00201019", "OBJECTIVE To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We conducted a r and omized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton , Canada . Pharmacists performed medication assessment s and limited history and physical examinations and provided guideline -concordant recommendations to optimize medication management . Follow-up contact was completed as necessary . Control patients received usual care . The primary outcome was a ≥10 % decrease in systolic blood pressure at 1 year . RESULTS A total of 260 patients were enrolled , 57 % were women , the mean age was 59 years , diabetes duration was 6 years , and blood pressure was 129/74 mmHg . Forty-eight of 131 ( 37 % ) intervention patients and 30 of 129 ( 23 % ) control patients achieved the primary outcome ( odds ratio 1.9 [ 95 % CI 1.1–3.3 ] ; P = 0.02 ) . Among 153 patients with inadequately controlled hypertension at baseline , intervention patients ( n = 82 ) were significantly more likely than control patients ( n = 71 ) to achieve the primary outcome ( 41 [ 50 % ] vs. 20 [ 28 % ] ; 2.6 [ 1.3–5.0 ] ; P = 0.007 ) and recommended blood pressure targets ( 44 [ 54 % ] vs. 21 [ 30 % ] ; 2.8 [ 1.4–5.4 ] ; P = 0.003 ) . The 10-year risk of cardiovascular disease , based on changes to the UK Prospect i ve Diabetes Study Risk Engine , were predicted to decrease by 3 % for intervention patients and 1 % for control patients ( P = 0.005 ) . CONCLUSIONS Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams , which suggests that pharmacists can make important contributions to the primary care of these patients", "ABSTRACT OBJECTIVE Evaluate the effectiveness of collaborative management of hypertension by primary care-pharmacist teams in community-based clinics . STUDY DESIGN A 12-month prospect i ve , single-blind , r and omized , controlled trial in the Providence Primary Care Research Network of patients with hypertension and uncontrolled blood pressure . METHODS As compared to usual primary care , intervention consisted of pharmacy practitioners participating in the active management of hypertension in the primary care office according to established collaborative treatment protocol s. At baseline , there was no significant difference in blood pressure between groups . Primary outcome measures were the differences in mean systolic and diastolic blood pressures between arms at study end . Secondary measures included blood pressure goal attainment ( RESULTS A total of 463 subjects were enrolled ( n = 233 control , n = 230 intervention ) . Subjects receiving the intervention achieved significantly lower systolic ( p = 0.007 ) and diastolic ( p = 0.002 ) blood pressures compared to control ( 137/75 mmHg vs. 143/78 mmHg ) . In addition , 62 % of intervention subjects achieved target blood pressure compared to 44 % of control subjects ( p = 0.003 ) . The intervention group received more total office visits ( 7.2 vs. 4.9 , p physician visits ( 3.2 vs. 4.7 , p antihypertensive medications ( 2.7 vs. 2.4 , p = 0.02 ) , but did not take more antihypertensive pills per day ( 2.4 vs. 2.5 , p = 0.87 ) . There were minimal differences between groups in hypertension-related knowledge , medication adherence , quality of life , or satisfaction . CONCLUSIONS Patients r and omized to collaborative primary care-pharmacist hypertension management achieved significantly better blood pressure control compared to usual care with no difference in quality of life or satisfaction", "Objective Studies have demonstrated that hypertension remains inadequately managed throughout the world , with lack of adherence to BP-lowering medication being a major factor . The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control . Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre , Covilhã , located in the Eastern Central Region of Portugal . Method This report evaluates the pharmacist ’s interventions during a prospect i ve r and omised controlled trial , from July 2009 to June 2010 . Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were r and omly allocated either to a control group ( no pharmaceutical care ) or to an intervention group ( quarterly follow-up by a hospital pharmacist during a 9-month period ) . The pharmacist interventions , aim ed to increase medication adherence and blood pressure control , involved educational interventions and counselling tips directed to the patient . Main outcome measure Systolic blood pressure , diastolic blood pressure and blood pressure control ( according to JNC 7 guidelines ) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures . Blood pressure measurements were performed by blinded nurses . Medication adherence was also evaluated , using a vali date d question naire at baseline and at the end of investigation . Results A total of 197 hypertensive patients were r and omly assigned to the study ( 99 in the control group and 98 in the intervention group ) . Although there were no significant differences ( P > 0.05 ) in both groups concerning mean age , gender , body mass index , and antihypertensive pharmacotherapy , blood pressure control was higher in the intervention group ( P = 0.005 ) at the end of the study . Significant lower systolic blood pressure ( −6.8 mmHg , P = 0.006 ) and diastolic blood pressure ( −2.9 mmHg , P = 0.020 ) levels were observed in the intervention group . Medication adherence was also significantly higher in the intervention group at the end of the study ( 74.5 % vs. 57.6 % , P = 0.012 ) . Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents", "BACKGROUND Blood pressure ( BP ) control in patients with diabetes mellitus is difficult to achieve and current patterns are suboptimal . Given increasing problems with access to primary care physicians , community pharmacists and nurses are well positioned to identify and observe these patients . This study aim ed to determine the efficacy of a community-based multidisciplinary intervention on BP control in patients with diabetes mellitus . METHODS We performed a r and omized controlled trial in 14 community pharmacies in Edmonton , Alberta , Canada , of patients with diabetes who had BPs higher than 130/80 mm Hg on 2 consecutive visits 2 weeks apart . Care from a pharmacist and nurse team included a wallet card with recorded BP measures , cardiovascular risk reduction education and counseling , a hypertension education pamphlet , referral to the patient 's primary care physician for further assessment or management , a 1-page local opinion leader-endorsed evidence summary sent to the physician reinforcing the guideline recommendations for the treatment of hypertension and diabetes , and 4 follow-up visits throughout 6 months . Control-arm patients received a BP wallet card , a pamphlet on diabetes , general diabetes advice , and usual care by their physician . The primary outcome measure was the difference in change in systolic BP between the 2 groups at 6 months . RESULTS A total of 227 eligible patients were r and omized to intervention and control arms between May 5 , 2005 , and September 1 , 2006 . The mean ( SD ) patient age was 64.9 ( 12.1 ) years , 59.9 % were male , and the mean ( SD ) baseline systolic/diastolic BP was 141.2 (13.9)/77.3 ( 8.9 ) mm Hg at baseline . The intervention group had an adjusted mean ( SE ) greater reduction in systolic BP at 6 months of 5.6 ( 2.1 ) mm Hg compared with controls ( P = .008 ) . In the subgroup of patients with a systolic BP greater than 160 mm Hg at baseline , BP was reduced by an adjusted mean ( SE ) of 24.1 ( 1.9 ) mm Hg more in intervention patients than in controls ( P patients who have diabetes and hypertension that are relatively well controlled , a pharmacist and nurse team-based intervention result ed in a clinical ly important improvement in BP . Trial Registration clinical trials.gov Identifier : NCT00374270", "Background : First Nations people with diabetes mellitus and hypertension are at greater risk of renal and cardiovascular complications than are non-native patients because of barriers to health care services . We conducted this r and omized controlled trial to assess whether a community-based treatment strategy implemented by home care nurses would be effective in controlling hypertension in First Nations people with existing hypertension and type 2 diabetes . Methods : We compared 2 community-based strategies for controlling hypertension in First Nations people with existing hypertension and diabetes . In the intervention group , a home care nurse followed a predefined treatment algorithm of pharmacologic antihypertensive therapy . In the control group , treatment decisions were made by each subject 's primary care physician . The primary outcome measure was the difference between the 2 groups in the change in systolic blood pressure after 12 months . Secondary outcome measures were the change in diastolic blood pressure over time , the change in urine albumin status and the incidence of adverse events . Results : Both groups experienced a significant reduction in systolic blood pressure by the final visit ( by 24.0 [ st and ard deviation ( SD ) 13.5 ] mm Hg in the intervention group and by 17.0 [ SD 18.6 ] mm Hg in the control group ) ; p diastolic blood pressure over time than did those in the control group ( by 11.6 [ SD 10.6 ] mm Hg v. 6.8 [ SD 11.1 ] mm Hg respectively ; p = 0.05 ) . The groups did not differ significantly in terms of changes in urine albumin excretion or incidence of adverse events . Interpretation : High rates of blood pressure control in the community were achieved in both groups in the DREAM 3 study . The addition of a home care nurse to implement a treatment strategy for blood pressure control was more effective in lowering diastolic than systolic blood pressure compared with home care visits for blood pressure monitoring alone and follow-up treatment by a family physician", "STUDY OBJECTIVE To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control . DESIGN Cluster-r and omized trial . SETTING Academic health system using an ambulatory electronic medical record . SUBJECTS A total of 10,696 patients with a diagnosis of hypertension cared for by 93 primary care providers . INTERVENTION Academic detailing , provision of provider-specific data about hypertension control , provision of educational material s to the provider , and provision of educational and motivational material s to patients . MEASUREMENTS AND MAIN RESULTS The primary outcome was blood pressure control , defined as a blood pressure measurement below 140/90 mm Hg , and was ascertained from electronic medical records over 6 months of follow-up . We determined the adjusted odds ratio for the association between the intervention and the achievement of controlled blood pressure . When we accounted for clustering by provider , this adjusted odds ratio was 1.13 ( 95 % confidence interval 0.87 - 1.47 ) . Adjusted odds ratios were 1.03 ( 95 % confidence interval 0.78 - 1.36 ) in patients whose blood pressure was controlled at baseline and 1.25 ( 95 % confidence interval 0.94 - 1.65 ) in those whose blood pressure was not . These odds ratios were not significantly different ( p=0.11 ) . CONCLUSIONS These results were consistent with no effect or , at best , a relatively modest effect of the intervention among patients with hypertension . Had we not included a concurrent control group , the data would have provided an unduly optimistic view of the effectiveness of the program . The effectiveness of future interventions may be improved by focusing on patients whose blood pressure is uncontrolled at baseline", "STUDY OBJECTIVES To examine potential threats to internal and external study validity caused by differential patient withdrawal from a r and omized controlled trial evaluating pharmacist management of hypertension , to compare the characteristics of patients who withdrew with those of patients who completed the study , and to identify characteristics that predispose patients to withdraw from hypertension management . DESIGN Prospect i ve , r and omized , comparative study . SETTING Network of primary care clinics . PATIENTS Four hundred sixty-three patients with a diagnosis of hypertension and a last documented systolic blood pressure of 160 mm Hg or greater and /or diastolic blood pressure of 100 mm Hg or greater . INTERVENTION Patients were r and omly allocated to the pharmacist intervention or usual-care ( control ) group . Those in the pharmacist intervention group were collaboratively managed by a primary care clinical pharmacy specialist and their primary care provider . Patients in the control group received usual care from only their primary care provider . MEASUREMENTS AND MAIN RESULTS Of the 463 patients , 191 ( 41 % ) withdrew from the study after r and omization and 272 ( 59 % ) completed the study . Patients who withdrew from the pharmacist intervention group were similar to patients who withdrew from the usual-care group with respect to age , sex , insurance status , and chronic conditions . Patients who smoked or had commercial insurance were more likely to withdraw from the study than the other participants . However , multivariate analysis of all variables , when adjusted for the effect of the intervention , revealed that insurance status was the only variable associated with a heightened probability of withdrawal ( p=0.002 ) . CONCLUSION Although this study had a high withdrawal rate , between-group patient characteristics remained balanced . Therefore , internal validity was preserved , and outcomes from the study groups could be reliably compared . A lack of significant differences between patients who withdrew versus those who completed , with the exception of insurance status , suggests that external validity was not jeopardized", "Background Hypertension affects 29 % of the adult U.S. population and is a leading cause of heart disease , stroke , and kidney failure . Despite numerous effective treatments , only 53 % of people with hypertension are at goal blood pressure . The chronic care model suggests that blood pressure control can be achieved by improving how patients and physicians address patient self-care . Methods and design This paper describes the protocol of a nested 2 × 2 r and omized controlled trial to test the separate and combined effects on systolic blood pressure of a behavioral intervention for patients and a quality improvement-type intervention for physicians . Primary care practice s were r and omly assigned to the physician intervention or to the physician control condition . Physician r and omization occurred at the clinic level . The physician intervention included training and performance monitoring . The training comprised 2 internet-based modules detailing both the JNC-7 hypertension guidelines and lifestyle modifications for hypertension . Performance data were collected for 18 months , and feedback was provided to physicians every 3 months . Patient participants in both intervention and control clinics were individually r and omized to the patient intervention or to usual care . The patient intervention consisted of a 6-month behavioral intervention conducted by trained interventionists in 20 group sessions , followed by 12 monthly phone contacts by community health advisors . Follow-up measurements were performed at 6 and 18 months . The primary outcome was the mean change in systolic blood pressure at 6 months . Secondary outcomes were diastolic blood pressure and the proportion of patients with adequate blood pressure control at 6 and 18 months . Discussion Overall , 8 practice s ( 4 per treatment group ) , 32 physicians ( 4 per practice ; 16 per treatment group ) , and 574 patients ( 289 control and 285 intervention ) were enrolled . Baseline characteristics of patients and providers and the challenges faced during study implementation are presented . The HIP interventions may improve blood pressure control and lower cardiovascular disease risk in a primary care practice setting by addressing key components of the chronic care model . The study design allows an assessment of the effectiveness and cost of physician and patient interventions separately , so that health care organizations can make informed decisions about implementation of 1 or both interventions in the context of local re sources .Trial registration Clinical Trials.gov identifier", "Background Patients with manifest vascular disease are at high risk of a new vascular event or death . Modification of classical risk factors is often not successful . We determined whether the extra care of a nurse practitioner could be beneficial to the cardiovascular risk profile of high-risk patients . Design We conducted a r and omized , controlled trial based on the Zelen design . Methods Two hundred and thirty-six patients with manifestations of a vascular disease and who had two or more modifiable vascular risk factors were pre-r and omized to receive treatment by a nurse practitioner plus usual care or usual care alone . After 1 year , risk factors were remeasured . The primary endpoint was achievement of treatment goals for blood pressure , lipid , glucose and homocysteine levels , body mass index , and smoking . Results Of the pre-r and omized patients , 95 of 119 ( 80 % ) in the intervention group and 80 of 117 ( 68 % ) in the control group participated in the study . After a mean follow-up of 14 months , the patients in the intervention group achieved significantly more treatment goals than did the patients in the control group ( systolic blood pressure 63 versus 37 % , total cholesterol 79 versus 61 % , low density lipoprotein-cholesterol 88 versus 67 % , and body mass index 38 versus 24 % ) . Medication use was increased in both groups and no differences were found in patients ' quality of life ( SF-36 ) at follow-up . Conclusion Treatment delivered by nurse practitioners , in addition to a vascular risk factor screening and prevention program , result ed in a better management of vascular risk factors than usual care alone in vascular patients after 1-year follow-up", "PURPOSE We wanted to examine whether integrating depression treatment into care for hypertension improved adherence to antidepressant and antihypertensive medications , depression outcomes , and blood pressure control among older primary care patients . METHODS Older adults prescribed pharmacotherapy for depression and hypertension from physicians at a large primary care practice in West Philadelphia were r and omly assigned to an integrated care intervention or usual care . Outcomes were assessed at baseline , 2 , 4 , and 6 weeks using the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression , an electronic monitor to measure blood pressure , and the Medication Event Monitoring System to assess adherence . RESULTS In all , 64 participants aged 50 to 80 years participated . Participants in the integrated care intervention had fewer depressive symptoms ( CES-D mean scores , intervention 9.9 vs usual care 19.3 ; P lower systolic blood pressure ( intervention 127.3 mm Hg vs usual care 141.3 mm Hg ; P lower diastolic blood pressure ( intervention 75.8 mm Hg vs usual care 85.0 mm Hg ; P adherence to an antidepressant medication ( intervention 71.9 % vs usual care 31.3 % ; P to an antihypertensive medication ( intervention 78.1 % vs usual care 31.3 % ; P improving patient outcomes . Integrated interventions may be more feasible and effective in real-world practice s , where there are competing dem and s for limited re sources", "PURPOSE To determine whether the type of health care provider ( i.e. , physician versus physician-nurse team ) affected the quality of hypertension care given to two groups of r and omly selected adult women . DATA SOURCES Three indicators measured the quality of hypertension care : blood pressure control level , knowledge of hypertension , and discussion about blood pressure medications with the health care provider(s ) . Blood pressure readings were taken with a 24-hr ambulatory blood pressure monitor , and demographic data from survey results taken at orientation and research er-collected data on posttreatment knowledge of hypertension and cognitive representations of hypertension were gathered . Chi-square and t tests were used to analyze the data . CONCLUSIONS The group whose care was managed by a physician-nurse team demonstrated lower means for 24-hr systolic blood pressure and diastolic blood pressure ( systolic : M = 132 , SD = 14.9 ; diastolic : M = 75 , SD = 11.3 ) than the group whose care was managed only by one or more physicians ( systolic : M = 136 , SD = 13.4 ; diastolic : M = 79 , SD = 11.24 ) . Also , the group whose care was managed by a physician-nurse team revealed significantly higher scores for discussion of blood pressure medication than the group whose care was managed only by one or more physicians . There were no group differences for knowledge of hypertension . IMPLICATION S FOR PRACTICE Nurses qualified to assist with meeting the needs of hypertension clients in primary care setting s can positively affect clients ' knowledge about blood pressure medication and --perhaps as a result of this knowledge -- how well the clients control their blood pressure", "OBJECTIVE To determine whether nurse case management with a therapeutic algorithm could effectively improve rates of control for hypertension , hyperglycemia , and hyperlipidemia compared with usual care among veterans with diabetes . RESEARCH DESIGN AND METHODS A r and omized controlled trial of diabetic patients that had blood pressure ( BP ) > 140/90 mmHg , hemoglobin A1c ( HbA1c ) > 9.0 % , or LDL > 100 mg/dL. Intervention patients received case management ( n = 278 ) versus usual care ( n = 278 ) over a 1-year period . The primary outcome was the percentage of patients achieving simultaneous control of all three parameters ( defined by BP included improvements within each individual component of the composite primary outcome . Differences between groups were analyzed using t tests , Pearson χ2 tests , and linear and logistic regression . RESULTS A greater number of individuals assigned to case management achieved the primary study outcome of having all three outcome measures under control ( 61 [ 21.9 % ] compared with 28 [ 10.1 % ] in the usual care group [ P individual treatment goals of HbA1c and BP LDL patients with diabetes , nurse case managers using a treatment algorithm can effectively improve the number of individuals with control of multiple cardiovascular risk factors at 1 year", "Background —Black subjects with a family history of premature coronary heart disease ( CHD ) have a marked excess risk , yet barriers prevent effective risk reduction . We tested a community-based multiple risk factor intervention ( community-based care [ CBC ] ) and compared it with “ enhanced ” primary care ( EPC ) to reduce CHD risk in high-risk black families . Methods and Results —Black 30- to 59-year-old siblings of a prob and with CHD aged EPC ( n=168 ) or CBC ( n=196 ) and monitored for 1 year . EPC and CBC were design ed to eliminate barriers to care . The CBC group received care by a nurse practitioner and a community health worker in a community setting . The CBC group was 2 times more likely to achieve goal levels of LDL cholesterol and blood pressure compared with the EPC group ( 95 % CI , 1.11 to 4.20 and 1.39 to 3.88 , respectively ) with adjustment for baseline levels of age , sex , education , and baseline use of medications . The CBC group demonstrated a significant reduction in global CHD risk , whereas no reduction was seen in the EPC group ( P reduce CHD risk in primary care setting s. An alternative community care model that addresses barriers may be a more effective way to ameliorate CHD risk in high-risk black families", "Despite widely publicized hypertension treatment guidelines for physicians and lifestyle recommendations for patients , blood pressure control rates remain low . In community-based primary care clinics , we performed a nested , 2 × 2 r and omized , controlled trial of physician intervention versus control and /or patient intervention versus control . Physician intervention included internet-based training , self-monitoring , and quarterly feedback reports . Patient intervention included 20 weekly group sessions followed by 12 monthly telephone counseling contacts and focused on weight loss , Dietary Approaches to Stop Hypertension dietary pattern , exercise , and reduced sodium intake . The primary outcome was change in systolic blood pressure at 6 months . Eight primary care practice s ( 32 physicians ) were r and omized to physician intervention or control groups . Within those practice s , 574 patients were r and omized to patient intervention or control groups . Patient mean age was 60 years , 61 % were women , and 37 % were black . Blood pressure data were available for 91 % of patients at 6 months . The main effect of physician intervention on systolic blood pressure at 6 months , adjusted for baseline pressure , was 0.3 mm Hg ( 95 % CI : −1.5 to 2.2 ; P=0.72 ) . The main effect of the patient intervention was −2.6 mm Hg ( 95 % CI : −4.4 to −0.7 ; P=0.01 ) . The interaction of the 2 interventions was significant ( P=0.03 ) ; the largest impact was observed with the combination of physician and patient intervention ( −9.7±12.7 mm Hg ) . Differences between treatment groups did not persist at 18 months . Combined physician and patient interventions lowers blood pressure ; future research should focus on enhancing effectiveness and sustainability of these interventions", "PURPOSE The present study evaluated whether an intervention using a short message service ( SMS ) by cellular phone and Internet would improve blood pressure , weight control , and serum lipids of obese patients with hypertension during 8 weeks . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the family medicine outpatient department of tertiary care hospital located in an urban city of South Korea . Twenty-eight patients were assigned to an intervention group and 21 to a control group . The goal of intervention was to bring blood pressure , body weight , and serum lipids levels close to normal ranges . Patients in the intervention group were requested to record their blood pressure and body weight in a weekly web based diary through the Internet or by cellular phones . The research ers sent optimal recommendations as an intervention to each patient , by both cellular phone and Internet weekly . The intervention was applied for 8 weeks . RESULTS Systolic ( SBP ) and diastolic blood pressures ( DBP ) significantly decreased by 9.1 and 7.2 mmHg respectively at 8 weeks from the baseline in the intervention group ( p SBP and DBP in the control group had not changed significantly . Yet , There were significant mean decreases in body weight and waist circumference by 1.6 kg ( p body weight and waist circumference ( p High density lipoprotein cholesterol ( HDL-C ) significantly increased , with a mean change of 3.7 mg/dl at 8 weeks from baseline in the intervention group ( p change of HDL-C in the control group was , however , not significant . CONCLUSION During 8 weeks using this web-based intervention by way of cellular phone and Internet SMS improved blood pressure , body weight , waist circumference , and HDL-C in patients with obese hypertension", "BACKGROUND Lack of medication adherence is a common reason for poor control of blood pressure in the community , increasing the risk of heart attacks and strokes . OBJECTIVE To evaluate the effect of nurse-led adherence support for people with uncontrolled high blood pressure compared with usual care . METHODS We recruited 245 women and men with uncontrolled hypertension ( > or = 150/90 mmHg ) from 21 general practice s in Bristol , UK . Participants were r and omized to receive nurse-led adherence support or usual care alone . Main outcome measures were adherence to medication ( ' timing compliance ' ) and blood pressure . RESULTS Mean baseline timing compliance ( + /- SD ) was high in both the intervention ( 90.8 + /- 15.6 % ) and the control group ( 94.5 + /- 7.6 % ) . There was no evidence of an effect of the intervention on timing compliance at follow-up ( adjusted difference in means -1.0 % ; 95 % confidence interval ( CI ) -5.1 to 3.1 ) . There was also no difference at follow-up between the groups with regard to systolic blood pressure ( -2.7 mmHg ; 95 % CI -7.2 to 1.8 ) or diastolic blood pressure ( 0.2 mmHg ; 95 % CI -1.9 to 2.3 ) . Projected costs for the primary care sector per consultation were 6.60 pound sterling for the intervention compared with 5.08 pound sterling for usual care . CONCLUSION In this study , adherence to blood pressure medication was much higher than previously reported . There was no evidence of an effect of nurse-led adherence support on medication adherence or blood pressure compared with usual care . Nurse-led adherence support was also more expensive from a primary care perspective", "OBJECTIVES To determine the long-term effect of a community-based risk reduction intervention at five years after completion of a one-year r and omized clinical trial and to determine the sustainability of the beneficial effects seen one year after the intervention . METHODS 30- to 59- year-old African American siblings of prob and s with premature coronary heart disease ( CHD ) were r and omized for care of multiple CHD risk factors to either one year of community-based care ( CBC ) provided by a nurse practitioner/community health worker team or enhanced usual care ( EUC ) . At five years , 307 ( 84.6 % ) of the siblings returned for reevaluation . MAIN OUTCOME MEASURES Changes in and achievement of goal levels of low-density lipoprotein cholesterol ( LDL-C ) , systolic and diastolic blood pressure ( SBP and DBP , respectively ) , and smoking cessation at five years . RESULTS No significant differences were seen between groups in mean LDL-C , SBP , and DBP or in the overall percentages achieving goal LDL-C , blood pressure , or smoking status . Changes after completion of the intervention suggest that the CBC group lost the beneficial effects for mean LDL-C and for percentage at goal LDL-C , while the EUC group continued to improve . CBC was associated with greater sustainability and less refractoriness of one-year results for LDL-C and blood pressure goals . CONCLUSIONS Although no group differences were found in mean risk factor levels at five years , data indicate that CBC is both feasible and associated with earlier sustainability of positive risk factor changes compared with EUC", "This study investigated the effectiveness of a community-academic health center partnership , utilizing nurse-supervised indigenous community health workers , in decreasing the blood pressure in an urban African-American population . A four-year r and omized clinical trial was conducted in the S and town-Winchester community , which has an excess prevalence of high blood pressure , in order to test the effectiveness of 2 different levels of intervention intensity on increasing the control of high blood pressure . Community health workers were trained and certified in blood pressure management , monitoring , education and counseling , social support mobilization , and community outreach and follow up . The primary results were a significant decrease in mean systolic and diastolic pressures after both levels of intervention , and a significant increase in the percentage of individuals with controlled high blood pressure . Surprisingly , no differences in results were observed between the 2 levels of intervention intensity . This study supports the use of community-based partnership efforts , and the utilization of indigenous health workers , to enhance the control of high blood pressure in a high-risk , African-American urban population", "BACKGROUND African American men with hypertension ( HTN ) in low socioeconomic urban environments continue to achieve poor rates of HTN control . METHODS In a 5-year r and omized clinical trial with 309 hypertensive urban African American men aged 21 to 54 years , the effectiveness of a more intensive educational/behavioral/pharmacologic intervention provided by a nurse practitioner/community health worker/physician team was compared to less intensive information and referral intervention . Changes in behavioral factors , health care utilization , blood pressure ( BP ) control , left ventricular hypertrophy ( LVH ) , and renal insufficiency were evaluated . RESULTS Follow-up rates exceeded 89 % of available men . The ranges of mean annual systolic BP/diastolic BP change from the baseline to each year follow-up were -3.7 to -10.1/-4.9 to -12.3 mm Hg for the more intensive group and + 3.4 to -3.0/-1.8 to -8.7 mm Hg for the less intensive group . The annual proportion of men with controlled BP ( LVH than the less intensive group and 17 % of the men were deceased primarily due to narcotic or alcohol intoxication ( 36 % ) and cardiovascular causes ( 19 % ) . CONCLUSIONS An appropriate educational/behavioral intervention significantly improved BP control and reduced some sequelae of HTN in a young African American male population . Improvement in risk factors other than HTN was limited and sustained control of HTN was difficult to maintain during 5 years", "BACKGROUND R and omized controlled trials have provided unequivocal evidence that treatment of hypertension decreases mortality and major disability from cardiovascular disease ; however , blood pressure remains inadequately treated in most affected individuals . This large gap continues despite the facts that more than 90 % of adults with hypertension have health insurance , and hypertension is the leading cause of visits to the doctor . New approaches are needed to improve hypertension care . OBJECTIVES The Electronic Communications and Home Blood Pressure Monitoring ( e-BP ) study is a three-arm r and omized controlled trial design ed to determine whether care based on the Chronic Care Model and delivered over the Internet improves hypertension care . The primary study outcomes are systolic , diastolic , and blood pressure control ; secondary outcomes are medication adherence , patient self-efficacy , satisfaction and quality of life , and healthcare utilization and costs . METHODS Hypertensive patients receiving care at Group Health medical centers are eligible if they have uncontrolled blood pressure on two screening visits and access to the Web and an e-mail address . Study participants are r and omly assigned to three intervention groups : ( a ) usual care ; ( b ) home blood pressure monitoring receipt and proficiency training on its use and the Group Health secure patient website ( with secure e-mail access to their healthcare provider , access to a shared medical record , prescription refill and other services ) ; or ( c ) this plus pharmacist care management ( collaborative care management between the patient , the pharmacist , and the patient 's physician via a secure patient website and the electronic medical record ) . CONCLUSION We will determine whether a new model of patient-centered care that leverages Web communications , self-monitoring , and collaborative care management improves hypertension control . If this model proves successful and cost-effective , similar interventions could be used to improve the care of large numbers of patients with uncontrolled hypertension", "This was a prospect i ve , cluster r and omized controlled trial in patients with uncontrolled hypertension aged 21 to 85 years ( mean , 61 years ) . Pharmacists made recommendations to physicians for patients in the intervention clinics ( n=101 ) but not patients in the control clinics ( n=78 ) . The mean adjusted difference in systolic blood pressure ( BP ) between the control and intervention groups was 8.7 mm Hg ( 95 % confidence interval [ CI ] , 4.4 - 12.9 ) , while the difference in diastolic BP was 5.4 mm Hg ( CI , 2.8 - 8.0 ) at 9 months . The 24-hour BP levels showed similar effects , with a mean systolic BP level that was 8.8 mm Hg lower ( CI , 5.0 - 12.6 ) and a mean diastolic BP level that was 4.6 mm Hg ( CI , 2.4 - 6.8 ) lower in the intervention group . BP was controlled in 89.1 % of patients in the intervention group and 52.9 % in the control group ( adjusted odds ratio , 8.9 ; CI , 3.8 - 20.7 ; P collaboration achieved significantly better mean BP values and overall BP control rates , primarily by intensification of medication therapy and improving patient adherence", "BACKGROUND Less than one third of the 65 million Americans with hypertension have adequate blood pressure ( BP ) control . This study examined the effectiveness of 2 interventions for improving patient BP control . METHODS This was a 2-level ( primary care provider and patient ) cluster r and omized trial with 2-year follow-up occurring among patients with hypertension enrolled from a Veterans Affairs Medical Center primary care clinic . Primary care providers ( n = 17 ) in the intervention received computer-generated decision support design ed to improve guideline concordant medical therapy at each visit ; control providers ( n = 15 ) received a reminder at each visit . Patients received usual care or a bimonthly tailored nurse-delivered behavioral telephone intervention to improve hypertension treatment . The primary outcome was proportion of patients who achieved a BP ( 816 eligible patients contacted , 190 refused and 38 were excluded . The 588 enrolled patients had a mean age of 63 years , 43 % had adequate baseline BP control , and 482 ( 82 % ) completed the 24-month follow-up . There were no significant differences in amount of change in BP control in the 3 intervention groups as compared to the hypertension reminder control group . In secondary analyses , rates of BP control for all patients receiving the patient behavioral intervention ( n = 294 ) improved from 40.1 % to 54.4 % at 24 months ( P = .03 ) ; patients in the nonbehavioral intervention group improved from 38.2 % to 43.9 % ( P = .38 ) , but there was no between-group differences at the end of the study . CONCLUSION The brief behavioral intervention showed improved outcomes over time , but there were not significant between group differences", "Increasing dem and to deliver and document therapeutic and preventive care sharpens the need for disease management strategies that accomplish these goals efficiently while preserving quality of care . The purpose of this study was to compare selected outcomes for a new chronic disease management program involving a nurse practitioner - physician team with those of an existing model of care . One hundred fifty-seven patients with hypertension and diabetes mellitus were r and omly assigned to their primary care physician and a nurse practitioner or their primary care physician alone . Costs for personnel directly involved in patient management , calculated from hourly rates and encounter time with patients , and pre- and post- study glycosylated hemoglobin ( HbA1c ) , high-density lipoprotein cholesterol ( HDL-c ) , satisfaction with care and health-related quality of life ( HRQoL ) were assessed . Although 1-year costs for personnel were higher in the team-treated group , participants experienced significant improvements in mean HbA1c ( − 0.7 % , p = 0.02 ) and HDL-c ( + 2.6 mg dL − 1 , p = 0.02 ) . Additionally , satisfaction with care improved significantly for team-treated subjects in several sub-scales whereas the mean change over time in HRQoL did not differ significantly between groups . This study demonstrates the value of a complementary team approach to chronic disease management in improving patient-derived and clinical outcomes at modest incremental costs", "BACKGROUND Few telemedicine programs have undergone cost analyses , impeding their implementation into practice . We report on the economic analysis of a nurse-administered intervention design ed to improve blood pressure control among hypertensive veterans . METHODS We r and omized hypertensive patients at the Durham Veterans Affairs Medical Center primary care clinic to behavioral ( n = 294 ) or nonbehavioral ( n = 294 ) interventions . Behavioral intervention patients received tailored information bimonthly for 2 years via telephone . To calculate intervention cost , we microcosted the nurse 's labor cost and computer hardware and software costs , applied a direct-to-indirect cost ratio , and distributed the costs over an estimated cohort of patients . We analyzed data from the Veterans Affairs Decision Support System to assess whether the intervention impacted overall health care utilization and costs . We used life expectancy estimates from the literature to develop decision models to calculate cost per life-year saved . RESULTS The mean annual intervention cost was $ 112 ( range $ 61-$259 ) . During 2 years of follow-up , patients in the intervention group incurred $ 7,800 in inpatient costs and $ 9,741 in outpatient costs ; the nonintervention group incurred $ 6,866 in inpatient costs and $ 9,599 in outpatient costs . The total cost difference was not statistically significant ( P = .56 ) . Cost-effectiveness of the behavioral intervention ranged from $ 42,457 per life-year saved for normal-weight women to $ 87,300 per life-year saved for normal-weight men . CONCLUSIONS The study results suggest that a nurse-administered , tailored behavioral intervention can be implemented at nominal cost and be cost-effective ; however , there was no apparent lowering of health care utilization and costs during the 2 years of follow-up", "Few data exist on the effectiveness of cardiovascular disease ( CVD ) risk-reduction programs in patients with limited access to health care . The objective of this project was to evaluate a disease management approach to multifactor CVD risk reduction in patients with limited or no health insurance and low family income . Patients ( n = 148 ) were recruited from not-for-profit or free clinics and hospitals and r and omized to usual care or usual care plus team case management . Mean age was 59.3 years , 57 % were women , 50 % had less than a high school education , 57 % were Hispanic , and 64 % had no health insurance . All had > or = 1 increased risk factor for CVD , and 24.5 % had documented coronary artery disease . Follow-up measurements were obtained at 6 and 12 months . Primary outcomes were low-density lipoprotein cholesterol and systolic blood pressure . The disease management program was supervised by a physician , delivered by nurses and dietitians , and included comprehensive lifestyle changes and medications . Data were collected on 91 % of patients at 12 months . Disease management produced clinical ly important decreases in selected risk factors compared with usual care , including systolic blood pressure ( p low-density lipoprotein cholesterol ( p excellent retention and lower CVD risk factors and demonstrated the potential of such approaches for decreasing long-term disease burden in selected medically underserved population", "OBJECTIVE To determine the effectiveness of specialist nurse-led clinics for hypertension and hyperlipidemia provided for diabetic patients receiving hospital-based care . RESEARCH DESIGN AND METHODS This study was a r and omized controlled implementation trial at Hope Hospital , Salford , U.K. The subjects consisted of 1,407 subjects presenting for annual review with raised blood pressure(>or=140/80 mmHg ) , raised total cholesterol ( > or=5.0 mmol/l ) , or both . Individuals with diabetes were r and omized to usual care or usual care with subsequent invitation to attend specialist nurse-led clinics . Nurses provided clinics for participants , with attendance every 4 - 6 weeks , until targets were achieved . Lifestyle advice and titration of drug therapies were provided according to the locally agreed upon guidelines . Patients with both conditions were eligible for enrollment in either or both clinics . At subsequent annual review , blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register . Data relating to deaths were obtained from the national strategic tracing service . The primary outcome was the odds ratio of achieving targets in hypertension and hyperlipidemia , attributable to the specialist nurse-led intervention . RESULTS Overall , specialist nurse-led clinics were associated with a significant improvement in patients achieving the target after 1 year ( odds ratio [ OR ] 1.37 [ 95 % CI 1.11 - 1.69 ] , P = 0.003 ) . This primary analysis revealed a borderline difference in effect between the two types of clinics ( test for interaction between groups : P = 0.06 ) . Secondary analysis , consistent with the prior beliefs of the health care professionals involved , suggested that targets were achieved more frequently in patients enrolled in the specialist nurse-led clinic for hyperlipidemia ( OR 1.69 [ 1.25 - 2.29 ] , P = 0.0007 ) than for hypertension ( OR 1.14 [ 0.86 - 1.51 ] , P = 0.37 ) . Intervention ( enrolled to either or both clinics ) was associated with a reduction in all-cause mortality ( OR 0.55 [ 0.32 - 0.92 ] , P = 0.02 ) . CONCLUSIONS This study provides good evidence to support the use of specialist nurse-led clinics as an effective adjunct to hospital-based care of patients with diabetes . If the st and ards of care recommended in the National Service Framework for Diabetes are to be achieved , then such proven methods for delivering care must be adopted", "Objective The aim of this study is to describe recommendations made by clinical pharmacists when co-managing hypertension with physicians . Setting Two family medicine clinics at a major teaching hospital in the mid-western United States . Method This report details the specific recommendations made by pharmacists during a prospect i ve r and omized controlled clinical trial . Patients with uncontrolled hypertension were enrolled in a 9-month intensive pharmacist – physician co-management study . Clinical pharmacists saw patients at baseline , 2 , 4 , 6 , and 8 month visits . Optional visits were allowed between required visits . Main outcome measure For this analysis , pharmacist recommendations were grouped . Physician acceptance of the pharmacists ’ recommendations was also evaluated . Results Data from 101 patients were included and analyzed in this study . Changes in drug therapy were recommended 267 times for these 101 patients . Most recommendations for a change in treatment involved adding a new antihypertensive medication ( 46.4 % ) or increasing a dose ( 33.3 % ) . The majority of pharmacist recommendations to modify drug therapy were made at the baseline visit ( 41.6 % ) , with 76.8 % of recommendations made by the 2 month visit . Physicians accepted and implemented 95.9 % of the 267 pharmacist recommendations to modify drug therapy . Pharmacists recommended no change in the treatment plan 361 times , most often because the patient ’s blood pressure ( BP ) had achieved the goal . Average BP decreased from 153.1 ± 10.0/84.9 ± 12.0 mmHg ( average ± SD ) at baseline to 124.2 ± 9.7/74.7 ± 9.6 mmHg ( P Conclusion Pharmacist recommendations for alterations in drug therapy generally occurred early in the course of the study and were largely to intensify therapy through higher dosages or additional medications . Pharmacist – physician co-management of BP is effective at reducing BP and improving BP control rates ", "Background : Nearly one in three adults in the United States has hypertension . Hypertension is one of the largest risk factors for cardiovascular diseases , and it is growing in prevalence , especially among African Americans . Objectives : To test the hypothesis that individuals who participate in usual care ( UC ) plus blood pressure ( BP ) telemonitoring ( TM ) will have a greater reduction in BP from baseline to 12-month follow-up than would individuals who receive UC only . Methods : A two-group , experimental , longitudinal design with block stratified r and omization for antihypertensive medication use was used . African Americans with hypertension were recruited through free BP screenings offered in the community . Data were collected through a structured interview and brief physical exam . Cross tabs , repeated measures analysis of variance , and independent t tests were used to analyze the study 's hypothesis . Results : The TM intervention group had a greater reduction in systolic BP ( 13.0 mm Hg ) than the enhanced UC group ( 7.5 mm Hg ; t = −2.09 , p = .04 ) from baseline to the 12-month follow-up . Although the TM intervention group had a greater reduction in diastolic BP ( 6.3 mm Hg ) compared with the enhanced UC group ( 4.1 mm Hg ) , the differences were not statistically significant ( t = −1.56 , p = .12 ) . Discussion : Telemonitoring of BP result ed in clinical ly and statistically significant reductions in systolic BP over a 12-month period ; if maintained over a longer period of time , the reductions could improve care and outcomes significantly for African Americans with hypertension", "BACKGROUND Group medical clinics ( GMCs ) are widely used in the management of diabetes and hypertension , but data on their effectiveness are limited . OBJECTIVE To test the effectiveness of GMCs in the management of comorbid diabetes and hypertension . DESIGN R and omized , controlled trial . ( Clinical Trials.gov registration number : NCT00286741 ) SETTING 2 Veterans Affairs Medical Centers in North Carolina and Virginia . PATIENTS 239 patients with poorly controlled diabetes ( hemoglobin A(1c ) [ HbA(1c ) ] level > or = 7.5 % ) and hypertension ( systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg ) . INTERVENTION Patients were r and omly assigned within each center to either attend a GMC or receive usual care . Clinics comprised 7 to 8 patients and a care team that consisted of a primary care general internist , a pharmacist , and a nurse or other certified diabetes educator . Each session included structured group interactions moderated by the educator . The pharmacist and physician adjusted medication to manage each patient 's HbA(1c ) level and blood pressure . MEASUREMENTS Hemoglobin A(1c ) level and systolic blood pressure , measured by blinded research personnel at baseline , study midpoint ( median , 6.8 months ) , and study completion ( median follow-up , 12.8 months ) . Linear mixed models , adjusted for clustering within GMCs , were used to compare HbA(1c ) levels and systolic blood pressure between the intervention and control groups . RESULTS Mean baseline systolic blood pressure and HbA(1c ) level were 152.9 mm Hg ( SD , 14.2 ) and 9.2 % ( SD , 1.4 ) , respectively . At the end of the study , mean systolic blood pressure improved by 13.7 mm Hg in the GMC group and 6.4 mm Hg in the usual care group ( P = 0.011 by linear mixed model ) , whereas mean HbA(1c ) level improved by 0.8 % in the GMC group and 0.5 % in the usual care group ( P = 0.159 ) . LIMITATION Measurements of effectiveness may have been limited by concomitant improvements in the usual care group that were due to co-intervention . CONCLUSION Group medical clinics are a potent strategy for improving blood pressure but not HbA(1c ) level in diabetic patients . PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs Health Services Research and Development Service", "BACKGROUND Uncontrolled hypertension is a major primary healthcare problem . AIM To investigate whether blood pressure ( BP ) control in primary care could be improved by nurses taking responsibility for managing hypertensive patients . METHODS R and omized trial with two groups : usual or intensive care . Patients diagnosed previously as hypertensive and with a systolic office BP greater than 140mmHg were r and omized to an intensive care programme managed by trained nurses or to usual care . The intensive care programme included a visit every 6 weeks to the general practitioner 's office , with st and ardized BP measurement , self-measurement training , risk factor checks and advice on BP reduction . The intervention lasted for 1 year . The primary endpoints were systolic BP obtained by 24-hour ambulatory BP monitoring after 1 year and the change compared with baseline . RESULTS Two hundred patients from 19 physicians were enrolled ( 102 in the intensive care group ) . Data on ambulatory BP were available from 140 patients . Systolic BP declined from 134.4+/-14.0 to 126.3+/-10.4mmHg in the intensive care group and from 132.4+/-13.5 to 128.2+/-13.0mmHg in the usual care group . There was no statistically significant difference in values after 1 year ( p=0.332 ) . The reduction in systolic BP was significantly greater in the intensive care group ( 7.6 vs 3.3mmHg in the usual care group ; p=0.036 ) . Similar results were observed for diastolic BP and day- and night-time measurements . CONCLUSIONS An intensive medical care programme in the office setting managed by trained nurses can improve BP control effectively . Nurses could take more responsibility for managing hypertensive patients", "Objective . To study the efficacy of telephone and mail intervention in therapeutic compliance among patients with mild to moderate hypertension . Design . A prospect i ve controlled multicenter clinical trial . Setting . Eighty‐five primary care centers in Spain , with a duration of 6 months . Patients . A total of 636 patients with newly diagnosed or uncontrolled hypertension were included . Interventions . The patients were r and omized and distributed between the following groups : ( i ) control ( CG ) – under routine clinical management ; ( ii ) mail intervention ( MIG ) – received a mailed message reinforcing compliance and reminding of the visits ( 15 days , 2 and 4 months ) ; ( iii ) telephone intervention ( TIG ) – received a telephone call at 15 days , then at 7 and 15 weeks . Main outcome measure . Five visits were scheduled , with the measurement of blood pressure and counting of tablets . Compliers were defined as subjects showing 80–110 % drug consumption . Calculations were made of mean percentage compliance ( MPC ) and compliers , mean blood pressure and percentage controlled subjects . Results . Five hundred and thirty‐eight patients completed the study ( 261 males ) ; 85.5 % were compliers ( CI = 82.5–88.5 ; n = 460 ) . The MPC was 95.1±19.6 % ( CI = 93.28–96.92 ) . The CG consisted of 182 individuals , MIG = 172 and TIG = 184 . Compliers represented 69.2 % of the CG ( CI 62.5–75.9 % ) , 91.3 % ( CI = 87.1–95.5 ) of the MIG ( p = 0.0001 ) and 96.2 % of the TIG ( CI 93.5–98.9 % ) ; the final MPC was 89.6%±15 in CG , 96.6%±12 in MIG and 99.1±26.8 in TIG ( p = 0.0001 ) . The percentage of controlled subjects was 47.2 % in CG ( CI = 40–54.4 ) , 61.3 % in MIG ( CI = 54.1–68.5 % ) and 63.3 % in TIG ( CI = 56.4–70.2 % ) ( p improving patient compliance in hypertension", "Background —Despite well-publicized guidelines on the appropriate management of cardiovascular disease and type 2 diabetes , the implementation of risk-reducing practice s remains poor . This report describes the results of a r and omized , controlled clinical trial evaluating the effectiveness of a comprehensive program of cardiovascular disease risk reduction delivered by nurse practitioner /community health worker ( NP/CHW ) teams versus enhanced usual care ( EUC ) to improve lipids , blood pressure , glycated hemoglobin ( HbA1c ) , and patient perceptions of the quality of their chronic illness care in patients in urban community health centers . Methods and Results —A total of 525 patients with documented cardiovascular disease , type 2 diabetes , hypercholesterolemia , or hypertension and levels of LDL cholesterol , blood pressure , or HbA1c that exceeded goals established by national guidelines were r and omly assigned to NP/CHW ( n=261 ) or EUC ( n=264 ) groups . The NP/CHW intervention included aggressive pharmacological management and tailored educational and behavioral counseling for lifestyle modification and problem solving to address barriers to adherence and control . Compared with EUC , patients in the NP/CHW group had significantly greater 12-month improvement in total cholesterol ( difference , 19.7 mg/dL ) , LDL cholesterol ( difference,15.9 mg/dL ) , triglycerides ( difference , 16.3 mg/dL ) , systolic blood pressure ( difference , 6.2 mm Hg ) , diastolic blood pressure ( difference , 3.1 mm Hg ) , HbA1c ( difference , 0.5 % ) , and perceptions of the quality of their chronic illness care ( difference , 1.2 points ) . Conclusions —An intervention delivered by an NP/CHW team using individualized treatment regimens based on treat-to-target algorithms can be an effective approach to improve risk factor status and perceptions of chronic illness care in high-risk patients . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00241904", "BACKGROUND To determine which of 3 interventions was most effective in improving blood pressure ( BP ) control , we performed a 4-arm r and omized trial with 18-month follow-up at the primary care clinics at a Veterans Affairs Medical Center . METHODS Eligible patients were r and omized to either usual care or 1 of 3 telephone-based intervention groups : ( 1 ) nurse-administered behavioral management , ( 2 ) nurse- and physician-administered medication management , or ( 3 ) a combination of both . Of the 1551 eligible patients , 593 individuals were r and omized ; 48 % were African American . The intervention telephone calls were triggered based on home BP values transmitted via telemonitoring devices . Behavioral management involved promotion of health behaviors . Medication management involved adjustment of medications by a study physician and nurse based on hypertension treatment guidelines . RESULTS The primary outcome was change in BP control measured at 6-month intervals over 18 months . Both the behavioral management and medication management alone showed significant improvements at 12 months-12.8 % ( 95 % confidence interval [ CI ] , 1.6%-24.1 % ) and 12.5 % ( 95 % CI , 1.3%-23.6 % ) , respectively-but not at 18 months . In subgroup analyses , among those with poor baseline BP control , systolic BP decreased in the combined intervention group by 14.8 mm Hg ( 95 % CI , -21.8 to -7.8 mm Hg ) at 12 months and 8.0 mm Hg ( 95 % CI , -15.5 to -0.5 mm Hg ) at 18 months , relative to usual care . CONCLUSIONS Overall intervention effects were moderate , but among individuals with poor BP control at baseline , the effects were larger . This study indicates the importance of identifying individuals most likely to benefit from potentially re source intensive programs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00237692", "OBJECTIVE To determine if a multimodal intervention composed of patient education , home blood pressure ( BP ) monitoring , BP measurement reporting to an interactive voice response ( IVR ) phone system , and clinical pharmacist follow-up improves BP control compared with usual care . STUDY DESIGN Prospect i ve study with patient enrollment , medication consultation and adjustment , remote BP monitoring , and follow-up at 6 months . METHODS This r and omized controlled trial was conducted at 3 healthcare systems in Denver , Colorado , including a large health maintenance organization , a Veterans Affairs medical center , and a county hospital . At each site , patients with uncontrolled BP were r and omized to the multimodal intervention vs usual care for 6 months , with the primary end point of BP reduction . RESULTS Of 338 patients r and omized , 283 ( 84 % ) completed the study , including 138 intervention patients and 145 usual care patients . Baseline BP was higher in the intervention group vs the usual care group ( 150.5/89.4 vs 143.8/85.3 mm Hg ) . At 6 months , BPs were similar in the intervention group vs the usual care group ( 137.4 vs 136.7 mm Hg , P = .85 for systolic ; 82.9 vs 81.1 mm Hg , P = .14 for diastolic ) . However , BP reductions were greater in the intervention group vs the usual care group ( −13.1 vs −7.1 mm Hg , P = .006 for systolic ; −6.5 vs −4.2 mm Hg , P = .07 for diastolic ) . Adherence to medications was similar between the 2 groups , but intervention patients had a greater increase in medication regimen intensity . CONCLUSIONS A multimodal intervention of patient education , home BP monitoring , BP measurement reporting to an IVR system , and clinical pharmacist follow-up achieved greater reductions in BP compared with usual care", "Electronic interactive technology is being used in medical care to enhance communication between the patient and health care provider , as well as the patient ’s performance of appropriate health behaviors . Research has demonstrated the value of technology in enhancing medication-taking behavior , capturing medicationtaking events , and generating reports to health care providers.1–4 These devices can capture other patient-specific information such as blood pressure , presence of symptoms , and functional status in “ real time ” rather than depending on patient recall at a later date . What is lacking in these studies is a clear view of how medication management devices fit with existing patient monitoring and feedback processes , which depend on the interaction between patients and their health care providers . Clinical endpoints are also lacking . We had the opportunity to conduct a pilot study of a medication management system that used patient-specific information to tailor the electronic interactive technology to each individual patient ’s needs and behaviors", "OBJECTIVE Concurrent peer review visits are structured office visits conducted by clinician peers of the primary care clinician that are specifically design ed to reduce competing dem and s , clinical inertia , and bias . We assessed whether a single concurrent peer review visit reduced clinical inertia and improved control of hypertension , hyperlipidemia , and diabetes control among underserved patients . METHODS We conducted a r and omized encouragement trial to evaluate concurrent peer review visits with a community health center . Seven hundred twenty-seven patients with hypertension , hyperlipidemia , and /or diabetes who were not at goal for systolic blood pressure ( SBP ) , low-density lipoprotein cholesterol ( LDL-C ) , and /or glycated hemoglobin ( A1c ) were r and omly assigned to an invitation to participate in a concurrent peer review visit or to usual care . We compared change in these measures using mixed models and rates of therapeutic intensification during concurrent peer review visits with control visits . RESULTS One hundred seventy-one patients completed a concurrent peer review visit . SBP improved significantly ( p concurrent peer review visits than among those who failed to respond to a concurrent peer review invitation or those r and omized to usual care . There were no differences seen for changes in LDL-C or A1c . Concurrent peer review visits were associated with statistically significant greater clinician intensification of blood pressure ( p lipid ( p diabetes ( p Concurrent peer review visits represent a promising strategy for improving blood pressure control and improving therapeutic intensification in community health centers", "BACKGROUND Increased emphasis is being placed on the critical need to control hypertension ( HTN ) in patients with diabetes . OBJECTIVE The objective of this study was to evaluate the efficacy of a nurse-managed home telehealth intervention to improve outcomes in veterans with comorbid diabetes and HTN . DESIGN A single-center , r and omized , controlled clinical trial design comparing two remote monitoring intensity levels and usual care in patients with type 2 diabetes and HTN being treated in primary care was used . MEASUREMENTS Primary outcomes were hemoglobin A1c and systolic blood pressure ( SBP ) ; secondary outcome was adherence . RESULTS Intervention subjects experienced decreased A1c during the 6-month intervention period compared with the control group , but 6 months after the intervention was withdrawn , the intervention groups were comparable with the control group . For SBP , the high-intensity subjects had a significant decrease in SBP compared with the other groups at 6 months and this pattern was maintained at 12 months . Adherence improved over time for all groups , but there were no differences among the three groups . LIMITATIONS Subjects had relatively good baseline control for A1c and SBP ; minorities and women were underrepresented . CONCLUSIONS Home telehealth provides an innovative and pragmatic approach to enhance earlier detection of key clinical symptoms requiring intervention . Transmission of education and advice to the patient on an ongoing basis with close surveillance by nurses can improve clinical outcomes in patients with comorbid chronic illness", "BACKGROUND We conducted a cluster r and omized controlled trial to examine the effectiveness of computerized decision support ( CDS ) design ed to improve hypertension care and outcomes in a racially diverse sample of primary care patients . METHODS We r and omized 2,027 adult patients receiving hypertension care in 14 primary care practice s to either 18 months of their physicians receiving CDS for each hypertensive patient or to usual care without computerized support for the control group . We assessed prescribing of guideline -recommended drug therapy and levels of blood pressure control for patients in each group and examined if the effects of the intervention differed by patients ’ race/ethnicity using interaction terms . MEASUREMENTS AND MAIN RESULTS Rates of blood pressure control were 42 % at baseline and 46 % at the outcome visit with no significant differences between groups . After adjustment for patients ’ demographic and clinical characteristics , number of prior visits , and levels of baseline blood pressure control , there were no differences between intervention groups in the odds of outcome blood pressure control . The use of CDS to providers significantly improved Joint National Committee ( JNC ) guideline adherent medication prescribing compared to usual care ( 7 % versus 5 % , P overall blood pressure control . Future work focusing on improvement of these interventions and the study of other practical interventions to reduce disparities in hypertension-related outcomes is needed", "BACKGROUND Most patient chronic disease self-management interventions target single-disease outcomes . We evaluated the effect of a tailored hypertension self-management intervention on the unintended targets of glycosylated hemoglobin ( HbA1c ) and low-density lipoprotein cholesterol ( LDL-C ) . METHODS We evaluated patients from the Veterans Study to Improve the Control of Hypertension , a 2-year r and omized controlled trial . Patients received either a hypertension self-management intervention delivered by a nurse over the telephone or usual care . Although the study focused on hypertension self-management , we compared changes in HbA1c among a subgroup of 216 patients with diabetes and LDL-C among 528 patients with measurements during the study period . Changes in these laboratory values over time were compared between the 2 treatment groups using linear mixed-effects models . RESULTS For the patients with diabetes , the hypertension self-management intervention result ed in a 0.46 % reduction in HbA1c over 2 years compared with usual care ( 95 % confidence interval , 0.04%-0.89 % ; P = .03 ) . For LDL-C , there was a minimal 0.9 mg/dL between-group difference that was not statistically significant ( 95 % confidence interval , -7.3 - 5.6 mg/dL ; P = .79 ) . CONCLUSIONS There was a significant effect of the self-management intervention on the unintended target of HbA1c , but not LDL-C. Chronic disease self-management interventions might have \" spill-over \" effects on patients ' comorbid chronic conditions", "M eeting the complex needs of patients with chronic illness or impairment is the single greatest challenge facing organized medical practice . Usual care is not doing the job ; dozens of surveys and audits have revealed that sizable proportions of chronically ill patients are not receiving effective therapy , have poor disease con- trol , and are unhappy with their care ( 1 ) . Results of r and omized trials also show that effective disease management programs can achieve substantially better outcomes than usual care , the control intervention . These trials , along with the ideas and efforts for improvement discussed in this issue , show that we can improve care and outcomes . As the articles suggest , these improvements will not come easily . If we are to improve care for most patients with chronic illness , the evidence strongly suggests that we reshape our ambulatory care systems for this purpose . Pri- mary care practice was largely design ed to provide ready access and care to patients with acute , varied problems , with an emphasis on triage and patient flow ; short appointments ; diagnosis and treatment of symptoms and signs ; reliance on laborato- ry investigations and prescriptions ; brief , didactic patient education ; and patient- initiated follow-up . Patients and families struggling with chronic illness have differ- ent needs , and these needs are unlikely to be met by an acute care organization and culture . They require planned , regular interactions with their caregivers , with a focus on function and prevention of exacerbations and complications . This interac- tion includes systematic assessment s , attention to treatment guidelines , and behav- iorally sophisticated support for the patient 's role as self-manager . These interactions must be linked through time by clinical ly relevant information systems and continu- ing follow-up initiated by the medical practice . Comprehensive System", "Purpose : In developing our Patient-Centered Team CareSM ( PCTC ) program , we design ed a Plan-of-Care ( POC ) tool to facilitate the physician-patient discussion for setting health goals . This study aim ed to determine the effectiveness of the POC tool in improving clinical outcomes . Methods : We compared baseline and 6-month or greater follow-up values for hemoglobin A1c ( HbA1c ) , low-density lipoprotein ( LDL ) , systolic blood pressure ( SP ) , diastolic blood pressure ( DP ) , and weight for PCTC patients ( intervention group ) and non-PCTC patients ( control group ) . For the intervention group , we also compared POC tool completeness scores ( 1 , low and 8 , high ) . Results : Of 1366 patients , 1110 ( 593 intervention , 517 control ) had baseline and follow-up clinical measures for analysis . After adjusting for demographics , significant effects occurred in the intervention group for HbA1c ( P = .0067 ) , LDL ( P = .012 ) , and DP ( P = .091 ) . For completeness of POC , a significant association occurred between more fully completed forms ( scores , 5 - 8 ) and change in HbA1c ( P SP ( P = .011 ) . Conclusion : Patients receiving a POC showed significant improvement in 3 of 5 clinical outcomes compared with those without the tool , and those with more fully completed forms had significant improvement in 2 of 5 clinical outcomes compared with those with partially completed forms", "BACKGROUND Only 31 % of Americans with hypertension have their blood pressure ( BP ) under effective control . We describe a study that tests 3 different interventions in a r and omized controlled trial using home BP telemedicine monitoring . METHODS A sample of hypertensive patients with poor BP control at baseline ( N = 600 ) are r and omized to 1 of 4 arms : ( 1 ) control group -- a group of hypertensive patients who receive usual care ; ( 2 ) nurse-administered tailored behavioral intervention ; ( 3 ) nurse-administered medication management according to a hypertension decision support system ; ( 4 ) combination of the 2 interventions . The interventions are triggered based on home BP values transmitted via telemonitoring devices over st and ard telephone lines . The tailored behavioral intervention involves promoting adherence with medication and health behaviors . Patients r and omized to the medication management or the combined arm have their hypertension regimen changed by the study team using a vali date d hypertension decision support system based on evidence -based hypertension treatment guidelines and individualized to patients ' comorbid illnesses . The primary outcome is BP control : control using traditional models of care , testing novel interventions in patients ' homes may improve access , quality , and outcomes", "OBJECTIVE To determine the effectiveness of specialist nurse delivered education in primary care to improve control of hypertension and hyperlipidaemia in patients with diabetes . DESIGN AND SETTING Practice -level r and omized controlled trial , Salford , Engl and . SUBJECTS From 44 practice s , 10 303 subjects presenting in general practice with raised blood pressure (= 140/80 mmHg ) , raised total cholesterol (= 5.0 mmol/l ) or both . INTERVENTIONS Practice s were r and omized to receive either the intervention for hyperlipidaemia or for hypertension ; practice s acted as control for the intervention not received . Specialist nurses arranged a schedule of visits with general practitioners and general practice nurses , reminding them of diabetes protocol s and clinical targets . They provided educational material s and protocol s used in secondary care for nurse and doctor interventions including stepping up pharmacotherapy when necessary . Practice s received a list of patients in their practice who were poorly controlled at their last annual review ; new and recalled patients were targeted . OUTCOME MEASURES At subsequent annual review , blood pressure and total cholesterol values were obtained from the Salford electronic diabetes register for patients from participating practice s. RESULTS Overall , specialist nurse-led educational outreach to primary care was associated with no improvement in patients achieving target after 1 year-odds ratio ( OR ) : 1.03 ( 95 % CI 0.95 - 1.11 ; P = 0.52 ) . Similar results were achieved with hyperlipidaemia OR : 1.04 ( 95 % CI 0.88 - 1.23 ; P = 0.62 ) and hypertension OR : 1.01 ( 95 % CI 0.80 - 1.27 ; P = 0.93 ) . CONCLUSION This study provides evidence that the use of specialist nurses to perform educational outreach to improve target adherence to patients with diabetes in primary care is not effective", "STUDY OBJECTIVE To assess the effects of evidence -based treatment suggestions for hypertension made to physicians and pharmacists using a comprehensive electronic medical record system . DESIGN R and omized controlled trial with a 2 x 2 factorial design of physician and pharmacist interventions , which result ed in four groups of patients : physician intervention only , pharmacist intervention only , intervention by physician and pharmacist , and intervention by neither physician nor pharmacist ( control ) . SETTING Academic primary care internal medicine practice . SUBJECTS Seven hundred twelve patients with uncomplicated hypertension . MEASUREMENTS AND MAIN RESULTS Suggestions were displayed to physicians on computer workstations used to write outpatient orders and to pharmacists when filling prescriptions . The primary end point was generic health-related quality of life . Secondary end points were symptom profile and side effects from antihypertensive drugs , number of emergency department visits and hospitalizations , blood pressure measurements , patient satisfaction with physicians and pharmacists , drug therapy compliance , and health care charges . In the control group , implementation of care changes in accordance with treatment suggestions was observed in 26 % of patients . In the intervention groups , compliance with suggestions was poor , with treatment suggestions implemented in 25 % of patients for whom suggestions were displayed only to pharmacists , 29 % of those for whom suggestions were displayed only to physicians , and 35 % of the group for whom both physicians and pharmacists received suggestions ( p=0.13 ) . Intergroup differences were neither statistically significant nor clinical ly relevant for generic health-related quality of life , symptom and side-effect profiles , number of emergency department visits and hospitalizations , blood pressure measurements , charges , or drug therapy compliance . CONCLUSION Computer-based intervention using a sophisticated electronic physician order-entry system failed to improve compliance with treatment suggestions or outcomes of patients with uncomplicated hypertension ", "BACKGROUND Hypertension disproportionately affects African Americans compared to whites , and it is the single most common explanation for the disparity in mortality between African Americans and whites . Adherence with antihypertensive medications can help reduce risk of negative hypertension-related outcomes . Motivational interviewing is a promising patient-centered approach for improving adherence in patients with chronic diseases . In this paper we describe the rationale and design of an ongoing r and omized controlled trial testing the effectiveness of motivational interviewing versus usual care in improving medication adherence among 190 African American uncontrolled hypertensive patients , who receive care in a primary care setting . METHODS The usual care group receives st and ard medical care , while those in the intervention group receive st and ard care plus four sessions of motivational interviewing at 3-month intervals for a period of 1 year . This technique consists of brief , patient-driven counseling sessions to facilitate initiation and maintenance of behavior change . The primary outcome is adherence to prescribed antihypertensive medication , assessed with the electronic medication events monitoring system ( MEMS ) and the Morisky self-report adherence question naire . Secondary outcomes are within-patient changes in blood pressure , self-efficacy , and intrinsic motivation between baseline and 12 months . We report the baseline sociodemographic and clinical characteristics of the participants . CONCLUSIONS Despite the potential utility of motivational interviewing , little is known about its effectiveness in improving medication adherence among hypertensive patients , especially African Americans . In addition to the baseline data this study has generated , this trial should provide data with which we can assess the effectiveness of this approach as a behavioral intervention", "BACKGROUND Among the 65 million Americans with hypertension , only approximately 31 % have their blood pressure under control ( blood pressure control have had limited success . OBJECTIVES A r and omized controlled health services intervention trial with a two by two design is being conducted to improve blood pressure control . This five-year trial evaluates two patient-directed interventions design ed to improve blood pressure control among patients diagnosed with hypertension in a community-based primary care setting . METHODS Patients are r and omized to one of four groups : usual care , home blood pressure monitoring , tailored behavioral self-management intervention that is administered via telephone by a nurse , or a combination of the home blood pressure monitoring and tailored behavioral intervention . Patients receiving the home blood pressure monitoring are trained in the use of an electronic blood pressure measurement device , are asked to measure their blood pressure 3 times/week , and send in two-month blood pressure recordings throughout the 24-month study duration . The behavioral intervention incorporates patients ' need assessment s and involves tailored behavioral and education modules to promote medication adherence and improve specific health behaviors . A nurse delivers all behavioral self-management modules over the telephone bi-monthly for 24 months . The primary outcome is the proportion of patients who achieve control of their blood pressure based on evidence -based guidelines ( for patients without diabetes blood pressure control , and the wide availability of effective treatment strategies , a majority of adults still do not have their blood pressure controlled . This study will be an important step in defining two explicit interventions to improve blood pressure control . To our knowledge , this study is the first to combine both a tailored behavioral self-management intervention and self-monitoring home blood pressure intervention to improve blood pressure control among patients in a primary care setting", "BACKGROUND Our aim was to investigate whether a nurse-coordinated multidisciplinary , family-based preventive cardiology programme could improve st and ards of preventive care in routine clinical practice . METHODS In a matched , cluster-r and omised , controlled trial in eight European countries , six pairs of hospitals and six pairs of general practice s were assigned to an intervention programme ( INT ) or usual care ( UC ) for patients with coronary heart disease or those at high risk of developing cardiovascular disease . The primary endpoints-measured at 1 year-were family-based lifestyle change ; management of blood pressure , lipids , and blood glucose to target concentrations ; and prescription of cardioprotective drugs . Analysis was by intention to treat . The trial is registered as IS RCT N 71715857 . FINDINGS 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC , respectively . In patients with coronary heart disease who smoked in the month before the event , 136 ( 58 % ) in the INT and 154 ( 47 % ) in the UC groups did not smoke 1 year afterwards ( difference in change 10.4 % , 95 % CI -0.3 to 21.2 , p=0.06 ) . Reduced consumption of saturated fat ( 196 [ 55 % ] vs 168 [ 40 % ] ; 17.3 % , 6.4 to 28.2 , p=0.009 ) , and increased consumption of fruit and vegetables ( 680 [ 72 % ] vs 349 [ 35 % ] ; 37.3 % , 18.1 to 56.5 , p=0.004 ) , and oily fish ( 156 [ 17 % ] vs 81 [ 8 % ] ; 8.9 % , 0.3 to 17.5 , p=0.04 ) at 1 year were greatest in the INT group . High-risk individuals and partners showed changes only for fruit and vegetables ( p=0.005 ) . Blood-pressure target of less than 140/90 mm Hg was attained by both coronary ( 615 [ 65 % ] vs 547 [ 55 % ] ; 10.4 % , 0.6 to 20.2 , p=0.04 ) and high-risk ( 586 [ 58 % ] vs 407 [ 41 % ] ; 16.9 % , 2.0 to 31.8 , p=0.03 ) patients in the INT groups . Achievement of total cholesterol of less than 5 mmol/L did not differ between groups , but in high-risk patients the difference in change from baseline to 1 year was 12.7 % ( 2.4 to 23.0 , p=0.02 ) in favour of INT . In the hospital group , prescriptions for statins were higher in the INT group ( 810 [ 86 % ] vs 794 [ 80 % ] ; 6.0 % , -0.5 to 11.5 , p=0.04 ) . In general practice s in the intervention groups , angiotensin-converting enzyme inhibitors ( 297 [ 29 % ] INT vs 196 [ 20 % ] UC ; 8.5 % , 1.8 to 15.2 , p=0.02 ) and statins ( 381 [ 37 % ] INT vs 232 [ 22 % ] UC ; 14.6 % , 2.5 to 26.7 , p=0.03 ) were more frequently prescribed . INTERPRETATION To achieve the potential for cardiovascular prevention , we need local preventive cardiology programmes adapted to individual countries , which are accessible by all hospitals and general practice s caring for coronary and high-risk patients", "BACKGROUND Poor medication adherence is a significant problem in hypertensive African Americans . Although motivational interviewing ( MINT ) is effective for adoption and maintenance of health behaviors in patients with chronic diseases , its effect on medication adherence remains untested in this population . METHODS This r and omized controlled trial tested the effect of a practice -based MINT counseling vs. usual care ( UC ) on medication adherence and blood pressure ( BP ) in 190 hypertensive African Americans ( 88 % women ; mean age 54 years ) . Patients were recruited from two community-based primary care practice s in New York City . The primary outcome was adherence measured by electronic pill monitors ; the secondary outcome was within-patient change in office BP from baseline to 12 months . RESULTS Baseline adherence was similar in both groups ( 56.2 and 56.6 % for MINT and UC , respectively , P = 0.94 ) . Based on intent-to-treat analysis using mixed-effects regression , a significant time x group interaction with model-predicted posttreatment adherence rates of 43 and 57 % were found in the UC and MINT groups , respectively ( P = 0.027 ) , with a between-group difference of 14 % ( 95 % confidence interval , -0.2 to -27 % ) . The between-group difference in systolic and diastolic BP was -6.1 mm Hg ( P = 0.065 ) and -1.4 mm Hg ( P = 0.465 ) , respectively , in favor of the MINT group . CONCLUSIONS A practice -based MINT counseling led to steady maintenance of medication adherence over time , compared to significant decline in adherence for UC patients . This effect was associated with a modest , nonsignificant trend toward a net reduction in systolic BP in favor of the MINT group", "OBJECTIVES A r and omized controlled trial involving a nurse administered patient-tailored intervention is being conducted to improve blood pressure ( BP ) control . METHODS Veterans with hypertension from an outpatient primary care clinic completed a baseline assessment and were r and omly allocated to either a nurse administered intervention or to usual care . In this ongoing study , intervention patients receive the tailored intervention bi-monthly for 2 years via telephone ; the goal of the intervention is to promote adherence with medication and improve health behaviors . Patient factors targeted for intervention include perceived risk of hypertension , memory , literacy , social support , patients ' relationship with their health care provider , side effects of therapy , pill refill , missed appointments , and health behaviors . RESULTS The sample r and omized to the nurse intervention consisted of 294 veterans with hypertension ( average age = 63 years ; 41 % African-American ) . A comparable sample of veterans was assigned to usual care ( n = 294 ) . We have maintained a 97 % retention rate for the first 12 months of the study . The average phone call has lasted 3.7 min ranging from less than 1 to 40 min . At 6-month post-enrollment , individuals receiving the nurse intervention had a greater increase in confidence with following hypertension treatment ( P adherence with prescribed hypertension regimen . The study includes both general and patient-tailored information based upon need assessment . The study design ensures internal validity as well as the ability to generalize study findings to the clinic setting", "BACKGROUND Pharmacist-physician comanagement of hypertension has been shown to improve office blood pressures ( BPs ) . We sought to describe the effect of such a model on 24-hour ambulatory BPs . METHODS We performed a prospect i ve , cluster-r and omized , controlled clinical trial , enrolling 179 patients with uncontrolled hypertension from 5 primary care clinics in Iowa City , Iowa . Patients were r and omized by clinic to receive pharmacist-physician collaborative management of hypertension ( intervention ) or usual care ( control ) for a 9-month period . In the intervention group , pharmacists helped patients to identify barriers to BP control , counseled on lifestyle and dietary modifications , and adjusted antihypertensive therapy in collaboration with the patients ' primary care providers . Patients were seen by pharmacists a minimum of every 2 months . Ambulatory BP was measured at baseline and at study end . RESULTS Baseline and end-of- study ambulatory BP profiles were evaluated for 175 patients . Mean ( SD ) ambulatory systolic BPs ( SBPs ) , reported in millimeters of mercury , were reduced more in the intervention group than in the control group : daytime change in ( Δ ) SBP , 15.2 ( 11.5 ) vs 5.5 ( 13.5 ) ( P their BP controlled at the end of the study ( 75.0 % vs 50.7 % ) ( P . CONCLUSION Pharmacist-physician collaborative management of hypertension achieved consistent and significantly greater reduction in 24-hour BP and a high rate of BP control . Trial Registration clinical trials.gov Identifier : NCT00201045", "CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease , but most hypertension remains inadequately controlled . OBJECTIVE To determine if a new model of care that uses patient Web services , home blood pressure ( BP ) monitoring , and pharmacist-assisted care improves BP control . DESIGN , SETTING , AND PARTICIPANTS A 3-group r and omized controlled trial , the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model . The trial was conducted at an integrated group practice in Washington state , enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access . Care was delivered over a secure patient Web site from June 2005 to December 2007 . INTERVENTIONS Participants were r and omly assigned to usual care , home BP monitoring and secure patient Web site training only , or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications . MAIN OUTCOME MEASURES Percentage of patients with controlled BP ( mm Hg ) and changes in systolic and diastolic BP at 12 months . RESULTS Of 778 patients , 730 ( 94 % ) completed the 1-year follow-up visit . Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP ( Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP ( 56 % ; 95 % CI , 49%-62 % ) compared with usual care ( P Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care . Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups . Compared with usual care , the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP ( -13.2 mm Hg [ 95 % CI , -19.2 to -7.1 ] ; P diastolic BP ( -4.6 mm Hg [ 95 % CI , -8.0 to -1.2 ] ; P improved BP control ( relative risk , 3.32 [ 95 % CI , 1.86 to 5.94 ] ; P Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension . Trial Registration clinical trials.gov Identifier : NCT00158639", "BACKGROUND The aim of the trial was to evaluate the effectiveness of a program of cooperation between physician and pharmacist to reduce cardiovascular risk factors in patients with mild to moderate hypertension by promoting better blood pressure ( BP ) control , appropriate changes in antihypertensive medications , and beneficial changes in lifestyle . METHODS The 132 subjects in this r and omized , controlled trial were in the age range of 40 - 79 years . The inclusion criteria were : systolic BP ( SBP ) ranging from 140 - 179 mm Hg and /or diastolic BP ( DBP ) ranging from 90 - 99 mm Hg and treatment-naive ( untreated for hypertension ) ; or on a regimen of medication for hypertension . Of these 132 subjects , 124 ( 94 % ) were already receiving treatment with antihypertensive medications . Equal numbers of subjects were r and omly assigned to one of two groups : a physician-pharmacist intervention group ( n = 66 ) and a control group ( n = 66 ) . RESULTS The 6-month follow-up rate was 97 % in both groups . At 6 months , the mean decrease in SBP/DBP , as measured at home in the morning , was 2.9/3.3 mm Hg in the intervention group relative to baseline ( P = 0.02 and P home morning SBP in the intervention group was not significantly greater than in the control group . However , the DBP decline was significantly greater in the intervention than control groups , which showed a mean decrease of 2.8 mm Hg ( confidence interval : -5.5 to -0.1 ; P = 0.04 ) . The percentage of patients in whom control of home morning BP was achieved was 53 % in the intervention group and 47 % in the control group ( P = 0.40 ) . A higher percentage of patients in the intervention group , relative to the control group , were able to reduce the use of antihypertensive medications ( 31 vs. 8 % , P additional medications or increases in dosage relative to the controls ( 11 vs. 28 % , P = 0.03 ) . Patients of the intervention group were more likely to show reduction in body mass index and sodium intake and to stop smoking , as compared with the control group . CONCLUSIONS A program of cooperation between physician and pharmacist was successful in reducing cardiovascular risk factors in patients with mild to moderate hypertension by promoting better blood pressure ( BP ) control , appropriate changes in antihypertensive medications , and beneficial changes in lifestyle ", "Team-based care can improve hypertension control . The purpose of the present study was to evaluate blood pressure ( BP ) control 18 months following the discontinuation of a physician-pharmacist collaborative intervention . This was a retrospective analysis of patients who had previously participated in a prospect i ve , cluster r and omized , controlled clinical trial . Six community-based family medicine offices were r and omized to control or intervention groups . Research nurses measured BPs using an automated device during the prospect i ve trial . The research nurses then abstract ed data from medical records , including BPs , medications , changes in therapy , and laboratory values for 18 months following the discontinuation of the 6-month prospect i ve trial . The study included 228 patients in the control ( n = 146 ) or intervention ( n = 82 ) groups . The control group contained more patients with diabetes or chronic kidney disease ( P were older ( P = .047 ) , and had more coexisting conditions ( P Systolic BP 9 months following discontinuation of the physician-pharmacist intervention was 137.2 ± 18.2 mm Hg and 129.8 ± 13.3 mm Hg in the control and intervention groups , respectively ( P = .0015 ) . BP control was maintained in 61 ( 41.8 % ) control patients and 55 ( 67.1 % ) intervention patients ( P = .0003 ) . At 18 months post-intervention , systolic BP was 138.1 ± 20.4 mm Hg and 130.0 ± 16.0 mm Hg in the control and intervention groups , respectively ( P = .023 ) . BP control was maintained in 53 ( 36.3 % ) control patients and 55 ( 67.1 % ) intervention patients at 18 months post-intervention ( P . BP control rates remained significantly higher following a physician-pharmacist intervention compared with usual care for 18 months after discontinuation of the intervention . This model has the potential value as a useful long-term strategy to benefit patients with hypertension" ]	41184320-06ff-11f0-808a-c43d1ab1c353
Background : Laparoscopic cholecystectomy has advantages over the open procedure for postoperative pain . However , a systematic review of postoperative pain management in this procedure has not been conducted . Methods : A systematic review was conducted according to the guidelines of the Cochrane Collaboration . R and omized studies examining the effect of medical or surgical interventions on linear pain scores in patients undergoing laparoscopic cholecystectomy were included . Qualitative and quantitative analyses were performed . Recommendations for patient care were derived from review of these data , evidence from other relevant procedures , and clinical practice observations collated by the Delphi method among the authors . Results : Sixty-nine r and omized trials were included and 77 reports were excluded . Recommendations are provided for preoperative analgesia , anesthetic and operative techniques , and intraoperative and postoperative analgesia . Conclusions : A step-up approach to the management of postoperative pain following laparoscopic cholecystectomy is recommended . This approach has been design ed to provide adequate analgesia while minimizing exposure to adverse events	[ "Background : The aims of the study were to evaluate costs and clinical characteristics of desflurane‐based anaesthetic maintenance versus propofol for outpatient cholecystectomy", "Background : Clonidine has been shown to reduce perioperative circulatory instability . This postoperative analgesic effect of clonidine was also known in previous studies . The aim of the study was to investigate the clinical efficiency of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy", "Sixteen otherwise healthy women undergoing cholecystectomy were r and omized to receive postoperative analgesia either by continuous infusion of papaveretum ( n = 8) , or by continuous interpleural infusion of bupivacaine ( n = 8) . Postoperative pain was assessed by linear analogue and ventilatory capacity . Changes in body protein were measured by in vivo neutron activation analysis . Clinical course was also noted . Pain scores were significantly lower in the interpleural group over the first 48 h ( P less than 0.02 ) . Ventilatory capacity was also significantly better for the first 24 h ( P less than 0.025 ) . There was no evidence of shortened postoperative ileus ; hospital stay and postoperative fatigue were similar for the two groups . Weight and protein losses over a 2 week period were similar in the two groups . It is concluded that the apparent advantages in patient comfort and mobility offered by interpleural infusion are most marked in the first 48 h postoperatively , with an advantage in ventilatory capacity over the first 24", "Abstract . After laparoscopic surgery carbon dioxide remains within the peritoneal cavity for a few days , commonly causing pain . This prospect i ve r and omized study was performed to determine the efficacy of intraperitoneal infusion of normal saline on postoperative pain after laparoscopic cholecystectomy . Altogether 300 patients were r and omly assigned to one of five groups of 60 patients each . Group A : control group , no peritoneal infusion , no subhepatic drain . Group B : no peritoneal infusion but a subhepatic closed drain was left for 24 hours . Group C : normal saline 25 to 30 ml/kg body weight at a temperature of 37 ° C was infused under the right hemidiaphragm and left in the peritoneal cavity . Group D : normal saline in a room temperature was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated . Group E : normal saline was infused and suctioned as in group D , but a subhepatic closed drain was left for 24 hours . Postoperatively , analgesic medication usage , nausea , vomiting , and pain scores were determined at 2 , 6 , 12 , 24 , 48 , and 72 hours ( during hospitalization and at home ) . Postoperative pain was reduced significantly ( p normal saline offered a detectable benefit to patients undergoing laparoscopic cholecystectomy . The beneficial effect was better when the fluid was suctioned after deflation of the pneumoperitoneum and even better when a subhepatic closed drain continued fluid suction during the first postoperative hours", "A r and omized , double-blind , placebo-controlled study of buprenorphine was carried out in 20 patients after cholecystectomy . The drug was given on \" patient dem and \" either i.m . ( 0.15 mg ) or sublingually ( 0.2 mg ) with a minimum dose interval of 30 min . Over the 24-h study period the mean dem and by the sublingual route was 0.8 mg ( range 0.6 - 1.2 mg ) and by the i.m . route 0.66 mg ( range 0.45 - 0.9 mg ) . Pain relief , by visual analogue scales and grading , was similar . Plasma buprenorphine concentrations varied more after sublingual administration . Either route was effective for the treatment of pain when administered by \" patient dem and \"", "We have compared , in a r and omized study , conventional carbon dioxide pneumoperitoneum with abdominal wall lift in 25 patients undergoing laparoscopic cholecystectomy . Intra-abdominal pressure ( IAP ) ( 11 ( SD 2 ) mm Hg vs 2.7 ( 9 ) mm Hg ) ( P total amount of carbon dioxide used ( 40 ( 23 ) litre vs 9 ( 7 ) litre ) ( P Pulmonary compliance was significantly greater ( P arterial pressures were lower with abdominal wall lift ( P femoral vein pressure increased ( P Postoperative drowsiness was of significantly longer duration in the conventional pneumoperitoneum group than in the abdominal wall lift group ( 98 ( 46 ) min vs 13 ( 34 ) min ) ( P Postoperative nausea and vomiting and right shoulder pain occurred more often in patients with conventional pneumoperitoneum ( P abdominal wall lift may be attributed to avoiding excessive carbon dioxide and high IAP", "BACKGROUND Since the time to peak analgesic effect of intravenous morphine can be longer than 40 - 60 min in volunteers , the goal of this study was to evaluate the effect of the timing of intraoperative morphine administration on early postoperative pain . METHODS A total of 120 adult patients undergoing laparoscopic cholecystectomy were studied . Anaesthesia was induced with remifentanil and etomi date and maintained with remifentanil and sevoflurane/nitrous oxide . Morphine 150 micrograms kg-1 was given r and omly at three different times during surgery , and a fourth group received placebo . Times to eyes opening and extubation were measured , and pain was evaluated in the post-anaesthesia care unit ( PACU ) using a visual analogue scale ( VAS ) . Morphine 2 - 3 mg was given when the VAS score was > or = 50 mm . The four groups were , according to the time elapsed from morphine administration to the end of surgery , group 1 ( n = 30 ) : placebo ; group 2 ( n = 33 ) : 40 min . RESULTS Recovery from anaesthesia and pain scores were similar in all groups . However , mean ( SD ) morphine consumption was 5.7 ( 4.7 ) mg in group 1 , 4.4 ( 4.2 ) mg in group 2 , 4.7 ( 4.7 ) mg in group 3 , and 2.2 ( 4.0 ) mg in group 4 ( P Morphine was required in only 38 % of patients in group 4 compared with 83 % , 67 % and 69 % in groups 1 , 2 , and 3 , respectively ( P morphine administration did not affect the early recovery from anaesthesia . However , the reduction in the number of patients requiring morphine in the PACU when morphine had been given more than 40 min before the end of surgery supports this practice , rather than administration closer to the end of surgery", "It is postulated that laparoscopic cholecystectomy as “ patient-friendly surgery ” leads to more comfort and in particular to less pain . A prospect i ve study on pain was performed on all patients undergoing the operation over the period of 1 year ( n=382 ) out of a series of more than 1,000 patients who have undergone the operation in our clinic . Pain was measured by a 100-point visual analogue scale ( VAS ) , by a five-point verbal rating scale , and by the consumption of analgesics . Pain was the most frequent symptom , both before and after the operation . The mean level of pain was 37 VAS points 5 h after the operation and declined to 16 points on the third day . In 106 patients ( 27.8 % ) the intensity of pain was higher than 50 VAS points . Analgesics were used by 282 patients ( 73.8 % ) , opioids by 112 ( 29.3 % ) . Pain was significantly higher in female than male patients ( P consumption of analgesics was similar in both groups . The most severe pain was localized to the abdominal wall wounds by 157 ( 41.1 % ) and to the right upper abdomen by 138 patients ( 36.1 % ) on the first postoperative day . Patients who needed opioids and /or had a pain level of > 50 VAS points ( n=138 ) had higher preoperative pain levels ( P=0.018 ) and preoperatively complained more frequently about nausea , vomiting , bloating , and a feeling of abdominal pressure ( P=0.003–0.031 ) . However , predictive values of these variables were too small to be of clinical benefit . The duration of operation , intraoperative events ( loss of bile , blood , or gallstones ) , and additional laparoscopic procedures ( adhesiolysis , lavage , extension of an incision , suture of fascia ) did not influence the intensity of postoperative pain . We conclude that laparoscopic cholecystectomy did cause significant postoperative pain in one-third of our patients only up to the first postoperative day . As predictors for high intensity of pain were not identified , pain should be monitored and analgesics should be delivered liberally", "Background Although laparoscopic cholecystectomy ( LC ) results in less pain then open cholecystectomy , it is not a pain-free procedure . The aim of this study was to test a new method of preemptive analgesia . Methods By simple r and omization 60 patients were assigned to two groups ( 30 in each group ) . Group A , the placebo group , received 200 ml of 0.9 % saline , and group B received 5 mg/kg of a local anesthetic solution ( ropivacaine ) in 200 ml of 0.9 % saline . Local anesthetic or place solution were administer before creation of the pneumoperitoneum . Results Pain intensity , as rated by visual analog and verbal rating scales , and stress response data were significantly less in the group receiving ropivacaine than in the placebo group . No patients in treatment group received an additional dose of analgesic , whereas two patients in placebo group needed an additional analgesic . Conclusions Our results support the clinical validity of preemptive analgesia , but the timing of intraperitoneal administration of local anesthetic is very important . Only application before creation of the pneumoperitoneum may preempt every neuronal central sensitization", "Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure . We undertook a r and omized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy . A series of 100 consecutive American Society of Anesthesiologists ( ASA ) I or II patients were r and omly assigned to intramuscular pethidine ( 54 patients ) or intraperitoneal pethidine ( 46 patients ) . Each was combined with intraperitoneal bupivacaine . The primary end-points were the pain and nausea scores at intervals after operation . All recruited patients completed the study . Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined ( pain at rest at 4 hours : 1.6±0.8 vs. 2.4±0.9 cm ; p total dose of pethidine administered via patient-controlled analgesia ( PCA ) during the first 24 hours after surgery was also significantly lower in this group ( total dose 50.9±3.9 vs. 55.9±4.4 mg ; p differences in the respiratory rate at any of the time periods . Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy . This was achieved at the expense of increased nausea but no significant increase in vomiting . The accessibility of this route of analgesia administration has implication s for patients undergoing laparoscopic procedures , particularly with the recent trend toward increased use of ambulatory techniques . RésuméLa cholécystectomie laparoscopique est réalisée dans le monde entier et peut être réalisée en ambulatoire . Nous avons comparé par une étude r and omisée les bénéfices de la pethidine en intraperitoneal comparée à la pethidine en intramusculaire pour l’analgésie postcholecystectomic laparoscopique . Cent patients consécutifs , ASA I ou II , ont été r and omisés pour recevoir soit de la pethidine en intra-musculaire ( 54 patients ) ou en intrapéritonéale ( 46 patients ) . De la bupivacaïne a été administrée en intrapéritonéale chez tous les patients . Les critères de jugement principaux et secondaires ont été les scores de la douleur et de la nausée à des intervalles successifs post-opératoires . Tous les patients inclus ont complété l’étude . La douleur au repos et lors des mouvements a été significativement moindre dans le groupe recevant de la pethidine en intrapéritonéale à chaque intervalle étudié [ douleur au repos à 4 heures : 1.6 ( 0.8 ) cm vs. 2.4 ( 0.9 ) cm ; p=0.001 ; douleur lors des mouvements à 4 heures : 2.1 ( 0.9 ) cm vs. 3.1 ( 1.2 ) cm ; p=0.001 ] . La dose totale de pethidine administrée via la PCA pendant les 24 premières heures après chirurgie a également été plus basse dans ce groupe [ dose totale 50.9 ( 3.9 ) mg vs. 55.9 ( 4.4 ) mg ; p=0.001 ] . Il n’y avait aucune différence statistiquement significative en ce qui concernait la fréquence respiratoire quel que soit le moment de l’étude . La pethidine en intrapéritonéale est supérieure à la pethidine en intramusculaire pour l’analgésie de la douleur post-cholécystectomie laparoscopique . Cette amélioration a été accomplie au prix de plus de nausées mais sans augmentation significative des vomissements . L’utilisation de cette route d’administration a des implication s importantes chez le patient opéré sous laparoscopic , en particulier , vu la tendance actuelle à élargir les indications de la chirurgie ambulatoire . ResumenLa colecistectomía laparoscópica es el procedimiento más empleado en cirugía ambulatoria . Efectuamos un estudio comparative aleatorio sobre los efectos , de la petidina intraperitoneal vs intramuscular , en la analgesia postcolecistectomía laparoscópica . 100 pacientes ASA I o II fueron aleatoriamente distribuidos en 2 grupos : petidina intramuscular ( n=54 ) y petidina intraperitoneal ( n=46 ) ; a este último grupo se le asoció bupivacaina intraperitoneal . Se investigaron el dolor y las nauseas durante el postoperatorio . Todos los pacientes completaron el estudio . El dolor postoperatorio tanto en reposo como con la movilización fue significativamente menor en el grupo de petidina intraperitoneal [ dolor en reposo a las 4 horas 1.6 ( 0.8 ) cm vs 2.4 ( 0.9 ) cm ; p dosis total de petidina administrada en las primeras 24 horas del periodo postoperatorio fue menor [ dosis total 50.9 ( 3.9 ) mg vs 55.9 ( 4.4 ) mg , p frecuencia respiratoria a lo largo del periodo postoperatorio . La analgesia proporcionada por la administración intraperitoneal de petidina es superior a la obtenida por inyección intramuscular , aunque se produzcan más nauseas pero sin que se incremente la frecuencia de vómitos . Dada la accesibilidad de esta vía para la administración de analgésicos este proceder debe tenerse muy en cuenta en las técnicas laparoscópicas , especialmente si se quiere incrementar la realización de las mismas de manera ambulatoria", "Abstract Background : Laparoscopic cholecystectomy using low-pressure pneumoperitoneum ( 8 mmHg ) minimizes adverse hemodynamic effects , reduces postoperative pain , and accelerates recovery . Similar cl aims are made for gasless laparoscopy using abdominal wall lifting . The aim of this study was to compare gasless laparoscopic cholecystectomy to low-pressure cholecystectomy with respect to postoperative pain and recovery . Methods : Thirty-six patients were r and omized to low-pressure or gasless laparoscopic cholecystectomy using a subcutaneous lifting system ( Laparotenser ) . Results : The characteristics of the patients were similar in the two groups . The procedure was completed in all patients in the low-pressure group , but two patients in the gasless group were converted to pneumoperitoneum . There were no significant differences in postoperative pain and analgesic consumption , but patients in the gasless group developed shoulder pain more frequently ( 50 % vs 11 % , p Gasless and low-pressure laparoscopic cholecystectomy were similar with respect to postoperative pain and recovery . The gasless technique provided inferior exposure and the operation took longer , but the technique may still have value in high-risk patients with cardiorespiratory disease", "The clinical effects , recovery characteristics , and costs of total intravenous anesthesia ( TIVA ) , sevoflurane , and isoflurane anesthesia have been measured in various out-patient operations , but have not been evaluated in patients undergoing laminectomy or discectomy . In the current study , the authors assessed the hemodynamic characteristics , recovery , and cost analyzes after laminectomy and discectomy operations , comparing TIVA , sevoflurane , and isoflurane anesthesia . Sixty American Society of Anesthesiologists I and II patients were r and omly divided into three groups , each consisting of 20 patients . Group I received propofol-alfentanil , Group 2 received sevoflurane-N2O , and Group 3 received isoflurane-N2O . At the end of surgery , the anesthetics were discontinued , and recovery from anesthesia was assessed by measuring the time until spontaneous eye opening and the time until response to verbal comm and s. The drug and delivery costs were calculated in United States dollars . No significant differences were found in the demographic data . Heart rate and mean arterial pressure decreased significantly after induction of anesthesia in the TIVA group , compared to the two other groups ( P fastest recovery was seen in the TIVA group . Incidences of postoperative nausea , vomiting , and pain were significantly reduced after TIVA ( P additional costs in the post-anesthesia care unit . However , the total cost was significantly higher in the TIVA group than in the sevoflurane and isoflurane groups ( $ 52.73 , $ 29.99 , and $ 24.14 , respectively ) ( P intraoperative cost but provided the most rapid recovery from anesthesia , and the least frequent postoperative side effects", "We have compared , in a r and omized study in 26 patients , immediate and late postoperative recovery after elective laparoscopic cholecystectomy using the gasless , mechanical abdominal wall lift method with conventional carbon dioxide pneumoperitoneum . After the gasless method , tracheal extubation was performed significantly earlier than after the conventional method ( P End-tidal carbon dioxide concentrations were significantly higher after pneumoperitoneum for 30 min after operation ( P total amount of carbon dioxide used and duration of drowsiness ( r = 0.61 , P Postoperative nausea and vomiting , and right shoulder pain occurred less often after the gasless method ( P Late recovery criteria ( ability to drink , void and walk ) in patients in the gasless group were fulfilled approximately 7 h earlier than in those in the pneumoperitoneum group ( P Gasless laparoscopic cholecystectomy result ed in more uneventful and faster immediate and late postoperative recovery than conventional carbon dioxide pneumoperitoneum", "An intravenous anesthetic drug , propofol was considered to pose antiemetic action . A r and omized controlled trial was conducted to evaluate whether propofol could effectively reduce post-operative nausea and vomiting ( PONV ) compared to thiopental-nitrous oxide ( N2O ) . One-hundred and eight patients undergoing outpatient gynecologic laparoscopy were assigned to receive 3 techniques of anesthesia ; thiopental-N2O ( T/N ) , propofol-N2O ( P/N ) and total intravenous anesthesia ( TIVA ) using propofol ( P/P ) . The results showed that in the early period ( 0 - 5 hours ) , post-operative nausea in T/N , P/N and P/P groups was 72 per cent , 44 per cent and 31 per cent , respectively ( P = 0.002 ) , and post-operative vomiting was 58 per cent , 36 per cent and 11 per cent respectively ( P = 0.00014 ) . Patients in the P/N and P/P groups experienced nausea less frequently than the T/N group [ relative risk ( RR ) = 0.62 , ( 95 % CI 0.41 - 0.93 ) and RR = 0.42 ( 0.25 - 0.72 ) respectively ] . Patients in the P/N and P/P groups experienced vomiting less frequently than the T/N group [ RR = 0.62 ( 0.37 - 1.04 ) and RR = 0.19 ( 0.07 - 0.5 ) respectively ] . Two patients in the T/N group were admitted because of severe nausea and vomiting . In conclusion , TIVA using propofol and propofol-N2O anesthesia can significantly reduce the incidence of PONV in the early period . Concerning the economic crisis of the country as well as the quality of care , propofol-N2O would be the most appropriate anesthetic of choice", "We assessed the peri‐operative analgesic efficiency of low‐dose intrathecal morphine combined with a low dose of bupivacaine after elective laparoscopic cholecystectomy since postoperative pain in such procedures , although less than after a conventional open technique , may be significant , particularly during the first 12–24 h. After informed consent , 34 ASA I or II patients were r and omly allocated to one of two groups to receive either a lumbar intrathecal injection of morphine ( 75 or 100 μg ) combined with 5 mg of isobaric bupivacaine ( spinal group ) or a subcutaneous injection of a saline solution ( control group ) . Intra‐operatively , opioid requirements , blood pressure response and heart rate changes after insufflation were recorded . Postoperatively , morphine requirements , pain scores and opioid‐related side‐effects were assessed by a physician blinded to the r and omisation . Intra‐operative opioid requirements did not differ significantly between groups . Mean ( SD ) postoperative morphine requirements were significantly lower in the spinal group [ 13 ( 10 ) vs. 23 ( 10 ) mg ; p = 0.04 ] as were postoperative pain scores ( p effective postoperative analgesia for elective laparoscopic cholecystectomy", "The clinical benefit of propofol anaesthesia in the prevention of postoperative nausea and vomiting ( PONV ) is still being eluci date d despite many studies to date . In this study 64 adult female patients scheduled for thyroidectomy received , in a r and omized double-blind fashion , propofol with air or isoflurane with nitrous oxide for maintenance of anaesthesia . The primary response variable was the presence or absence of vomiting in the first six hours . A group sequential design was used to allow interim analysis . After 64 patients , the fourth analysis showed that fewer patients receiving propofol vomited or required an anti-emetic during the first six hours ( P no significant difference detected in the 6 to 24 hour interval . In this group of female patients , total intravenous anaesthesia ( TIVA ) with propofol is associated with an early reduction in early postoperative vomiting compared with st and ard inhalational techniques . This reduction in vomiting does not appear to persist beyond the first six hours", "UNLABELLED This study , conducted before and after the implementation of an acute pain service ( APS ) in a 1000-bed hospital , describes the process of the implementation of an APS . The nursing , anesthesia , and surgery departments were involved . In this study we sought to evaluate the results of a continuous quality improvement program by defining quality indicators and using quality tools . A quality program in accordance with current st and ards of acute pain treatment ( multimodal ) was worked out to enhance pain relief for all surgical in patients . A survey of nurses ' knowledge with regard to postoperative pain was conducted , and a visual analog scale ( VAS ) was introduced to assess pain intensity . Both nurses and physicians became familiar with evidence -based guidelines concerning postoperative pain . The entire process was monitored in three consecutive surveys and enrolled 2383 surgical in patients . Pain indicators based on VAS and analgesic consumption were recorded during the first 72 postoperative hours . After a baseline survey about current practice s of pain treatment , a nurse-based , anesthesiologist-supervised APS was implemented . The improvement in pain relief , expressed as VAS scores , was assessed in two further surveys . A quality manual was written and implemented . A major improvement in pain scores was observed after the APS inception ( P pain assessment by a visual analog scale , st and ard multimodal pain treatment , and continuous quality evaluation , improved postoperative pain relief . Establishing teams of surgeons , anesthesiologists , and nurses is the prerequisite for this improvement", "The main objectives of minisite cholecystectomy ( MC ) are to have smaller incisions , better cosmetic results , less trauma , and a lower morbidity rate . This prospect i ve r and omized study compares MC with conventional laparoscopic cholecystectomy ( CLC ) in terms of surgical trauma and cosmetic results in 44 patients . Conversion from MC to CLC was required in five patients . No conversion to open surgery was needed in the CLC group . The average operating time was slightly longer in the MC group , but the difference was not statistically significant ( 81 minutes versus 72 minutes , p=0.22 ) . The population characteristics , postoperative respiratory function measurements , pain scores , and analgesic requirements were similar in the two groups . The average score for scar tissue was significantly lower in the MC group ( 0.73 versus 1.93 , p=0.0045 ) . Only the cosmetic results of MC were superior to CLC . This technique could be a feasible alternative procedure in patients seeking better cosmetic results . However , further studies with larger sample sizes are needed to evaluate the postoperative morbidity of MC.RésuméLes objectifs principaux de la cholécystectomie laparoscopique minime ( CM ) ( par mini-trocars ) sont de réaliser de plus petites incisions , d’obtenir un meilleur résultat esthétique , de provoquer moins de trauma et d’avoir un taux plus bas de morbidité que la cholécystectomie par laparoscopic classique . Cette étude prospect i ve r and omisée a comparé la CM à la cholécystectomie par laparoscopic ( CL ) traditionnelle en termes de traumatisme chirurgical et de résultat esthétique chez 44 patients . On a du convertir la CM en CL chez cinq patients . Aucune conversion vers la chirurgie ouverte n’a été nécessaire dans le groupe de CL traditionnelle . Le temps moyen d’intervention a été plus long dans le groupe CM mais cette différence n’était pas statistiquement significative ( 81 min vs. 72 min , p=0.22 ) . Les caractéristiques de la population , les fonctions respiratoires , les scores de la douleur et les besoins en analgésiques étaient similaires dans les deux groupes . Les scores moyens d’évaluation de la cicatrice ont été significativement plus bas dans le groupe CM ( 0.73 vs. 1.93 , p=0.0045 ) . Seuls les résultats esthétiques de la CM étaient supérieurs à la CL . Cette technique pourrait être une alternative valable chez les patients cherchant une amélioration des résultats esthétiques . Cependant , d’autres études avec des échantillons plus larges sont nécessaires pour évaluer la morbidité postopératoire de la CM.ResumenEl propósito principal de la colecistectomía de invasión mínima ( CIM ) es lograr una cicatriz pequeña , mejor apariencia estética , menos trauma y morbilidad reducida . El présente estudio prospect i ve y aleatorizado compara la CIM con la colecistectomía laparoscópica convencional ( CLC ) en cuanto a trauma operatorio y result ado estético en 44 pacientes . Se requirió conversión de CIM a CLC en cinco pacientes , pero ninguna CLC tuvo que ser convertida a cirugía abierta . El promedio del tiempo operatorio fue ligeramente más prolongado en la CIM , pero la diferencia no es estadísticamente significativa ( 81 min versus 72 min , p=0.22 ) . Las características demográficas de los dos grupos eran similares y las determinaciones postoperatorias de función respiratoria , grado de dolor y requerimiento analgésico fueron sensiblemente iguales . El grado de tejido cicatricial fue significatamente menor en el grupo de la CIM ( 0.73 versus 1.93 , p=0.0045 ) . Sólo el result ado estético de la CIM fue superior al de la CLC . Esta técnica podría ser una alternativa factible en pacientes que busquen un mejor result ado estético . Sin embargo , se requieren estudios adicionales y grupos de pacientes más numerosos para evaluar la morbilidad postoperatoria de la CIM", "BACKGROUND Shoulder pain is common after laparoscopic cholecystectomy ( 60.5 % ) and can delay return to normal activities . The cause is unclear but may involve referral of pain from the traumatized area . PATIENTS AND METHODS A total of 75 patients with chronic cholecystitis who underwent laparoscopic cholecystectomy were r and omized into two groups . Group I ( 37 patients ) had 10 mL of 0.25 % bupivacaine instilled into the gallbladder bed and Calot 's triangle area at the end of cholecystectomy . Group II ( 38 patients ) served as controls and had no bupivacaine instillation . Postoperative shoulder pain was evaluated . RESULTS Six patients in Group I developed shoulder pain ( 16 % ) compared with 23 patients in Group II ( 60.5 % ) . The difference was statistically significant ( P = 0.0002 ) . CONCLUSION The raw area of the removed organ is at least partially responsible for shoulder pain after laparoscopic cholecystectomy . Local bupivacaine is effective in reducing such pain", " Postoperative shoulder‐tip pain occurs frequently following laparoscopic cholecystectomy . The aim of this r and omized clinical trial was to evaluate the efficacy of a low‐pressure carbon dioxide pneumoperitoneum during laparoscopic surgery in reducing the incidence of postoperative shoulder‐tip pain", "Research confirms that laparoscopic cholecystectomy ( LC ) results in shorter lengths of hospital stay and earlier return to usual activity than the traditional cholecystectomy procedure . Research in this area , however , focuses more on the medical aspects of patient recovery , but very few studies have evaluated how these patients manage their recovery at home or what types of problems they encounter . A total of 28 LC patients were r and omly assigned to two groups : ( 1 ) 23 h stay ( overnight ) in a general surgical ward or ( 2 ) day procedure unit ( DPU ) stay . Data was collected by a self-administered Postoperative Symptoms Diary and telephone interview . Results showed no significant difference between the two groups of patients recovery symptoms scores . Problems with mobility , pain and elimination recorded the highest mean scores for both groups of patients . Overnight patients also experienced problems with tiredness and eating . All DPU patients were able to manage their postoperative symptoms , compared to only 44 % of patients who had stayed in overnight . Carer assistance was needed with regard to activities of daily living , child care and reassurance . Results showed that with careful selection of patients , LC cases performed as day procedures did not impact at all on the patients ' recovery trajectory", "BACKGROUND Downsizing the port incisions may reduce pain after laparoscopic cholecystectomy . METHODS In a double-blind controlled study , 60 patients were r and omized to undergo either microlaparoscopic cholecystectomy using one 10-mm and three 3.5-mm trocars ( 3.5-mm LC ) or traditional laparoscopic cholecystectomy using two 10-mm and two 5-mm trocars ( LC ) . Incisional pain at each port incision and overall pain were recorded for 1 week after the operation . Fatigue , nausea and vomiting , pulmonary function , and cosmetic results were also measured . RESULTS Data from 52 patients were analyzed ; eight patients were excluded from the study for various reasons . One patient was converted from 3.5-mm LC to LC due to technical problems with the 3.5-mm optic . In the 3.5-mm LC group ( n = 25 ) , incisional pain was significantly decreased in the 1st postoperative week as compared with the LC group ( n = 27 ) ( p pain scores at the supraumbilical 10-mm port were significantly higher compared with other port sites ( p cosmetic results were significantly better in the 3.5-mm LC group ( p LC , and it both reduces incisional pain and improves the cosmetic result", "Laparoscopy approach to cholecystectomy has shortened the recovery period , reducing discharge times from 1 to 3 days to same-day discharge . We hypothesize that the use of more than one modality to prevent postoperative pain may be more efficacious than single modality . Patients were r and omized to a treatment ( n = 24 ) or control ( n = 25 ) group and studied using a prospect i ve , double-blind design . Preoperatively , at 45 min before induction of anesthesia , the treatment group received an intramuscular ( IM ) bolus injection of meperidine 0.6 mg/kg and ketorolac 0.5 mg/kg . The control group received two bolus IM injections of placebo ( normal saline ) . Ten minutes before incision , local anesthesia ( treatment group ) or saline ( control group ) was infiltrated into the skin of each patient . Anesthetic management , postoperative pain , and nausea treatment were st and ardized . Pain and nausea assessment were done 1 h preoperatively , 0 , 0.5 , 1 , 2 , 3 , and 4 h postoperatively , at discharge , and 10 , 24 , and 48 h postoperatively . Patients were discharged by scoring criteria . Postoperatively , significantly more patients in the treatment group were without pain on arrival in the postanesthesia care unit ( PACU ) , 12/21 ( 57.1 % ) vs 1/24 ( 4.2 % ) in the control group ( P severity of pain was sixfold less in the treatment group than in the control group . The incidence of nausea in the PACU was significantly less in the treatment group ; 4.7 % vs 29.5 % in the control group ( P Postanesthesia Discharge Score significantly earlier than those in the control group ( 281 + /- 12 min vs 375 + /- 19 min ; P recovery and discharge . ( Anesth Analg 1996;82:44 - 51", "Background and Aim : Postoperative pain is an important surgical problem . Recent studies in pain pathophysiology have led to the hypothesis that with pre-operative administration of analgesics ( pre-emptive analgesia ) it may be possible to prevent or reduce postoperative pain . This study was planned to investigate the efficacy of pre-emptive analgesia on postoperative pain after laparoscopic cholecystectomy . Methods : 45 patients undergoing laparoscopic cholecystectomy were r and omized into three groups . Bupivacaine was injected into the area of skin incision before trocar entry and after trocar removal in group 1 and 2 , respectively ; however , this procedure was not applied to the control group . The pain score of the patients was evaluated by the visual analogue scale ( VAS ) at 1 , 4 , 12 and 24 h after surgery . The daily analgesic requirement was evaluated in terms of diclophenac sodium ( Diclomec , Abdi Ibrahim , 75 mg ) intake/day . Analgesics were given to the patients whose VAS was 5 or higher . Results : While there was no significant difference in VAS scores between group 1 and 2 , the mean pain scores of these two groups were found to be significantly lower than of the control group although the analgesic requirement of the patients in each group was not statistically significant . Conclusion : Pre-emptive analgesia is as effective as postsurgical local anaesthesia in reducing postoperative pain", "Abstract Background : Reports suggest that the insufflation of cold gas to produce a pneumoperitoneum for laparoscopic surgery can lead to an intraoperative decrease in core body temperature and increased postoperative pain . Methods : In a r and omized controlled trial with 20 patients undergoing laparoscopic cholecystectomy , the effect of insufflation using carbon dioxide gas warmed to 37 ° C ( group W ) was compared with insufflation using room-temperature cold ( 21 ° C ) gas ( group C ) . Intraoperative body core and intra-abdominal temperatures were determined at the beginning and end of surgery . Postoperative pain intensity was evaluated using a visual analog scale and recording the consumption of analgesics . Results : There were no significant group-specific differences during the operation , neither in body temperature ( group W : 36.1 ± 0.4 ° C vs group C : 35.7 ± 0.6 ° C ) nor in intra-abdominal temperature ( group W : 35.9 ± 0.3 ° C vs group C : 35.6 ± 0.6 ° C ) . Postoperatively , the two groups did not differ in pain susceptibility and need of analgesics . Conclusion : The use of carbon dioxide gas warmed to body temperature to produce a pneumoperitoneum during short-term laparoscopic surgery has no clinical ly important effect", "& NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely", "This study tested the hypothesis that , by the addition of parenteral ketorolac to an oral analgesic regimen for one day following laparoscopic surgery , analgesia would be improved and thus the return of normal function hastened . Seventy-two female patients were r and omly assigned to receive ketorolac 10.5 mg subcutaneously at the end of surgery followed by a subcutaneous infusion of 1.75 mg/h for 24 to 36 hours , or an equivalent volume of saline . All patients were provided with codeine tablets ( 30 mg ) for analgesia if required . For the first four postoperative days patients recorded details of pain , side-effects and discomfort on performing everyday activities . Patients who received ketorolac received significantly less fentanyl in the Recovery Ward and significantly less codeine prior to discharge than the saline group . They also took significantly fewer codeine tablets over the four-day postoperative period . Pain scores in the ketorolac group were not significantly lower than in the saline group on the first postoperative day ( P=0.052 ) and subsequently remained similar . Levels of discomfort on performing six common activities were similar in the two groups over the four-day postoperative period . We conclude that , despite beneficial effects during the period of ketorolac administration , there was no continuing benefit after this time other than reduced analgesic use , and no improvement in the patients ’ ability to perform common activities", "BACKGROUND To investigate the clinical efficacy of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy ( LC ) . METHODS One hundred and ten patients , scheduled for elective laparoscopic cholecystectomy , were recruited for the prospect i ve , r and omized , single-blind , comparative study . They were r and omly allotted to either of the placebo or clonidine group . Patients of the placebo group ( n = 65 ) were premedicated with oral antacid ( alugel hydroxide 300 mg ) , while those in the clonidine group ( n = 45 ) were premedicated with oral clonidine 150 micrograms prior to anesthesia . The premedication was given 60 to 90 min before the anticipated time of induction of anesthesia . Normocapnia was maintained throughout the perioperative period . Mass spectrometer was used to assess the inspired and expiratory concentrations of isoflurane , the anesthetic used for maintenance of anesthesia . Postoperative pain intensity , sedation scores , adverse events , time to the first dose of postoperative analgesic and cumulative analgesic requirement in 24 hours were recorded . Data were expressed as mean + /- SD . RESULTS Patients in the clonidine group displayed greater hemodynamic stability perioperatively and the isoflurane requirement was also reduced ( 30 % less ) . The postoperative analgesic requirement was less ( 1.5 + /- 1.3 vs. 2.2 + /- 1.3 dose , P time for the first dose of analgesic was prolonged ( 411 + /- 565 vs. 264 + /- 441 min ) in comparison with the placebo group but no statistic difference was found . CONCLUSIONS Oral clonidine premedication helped to provide perioperative hemodynamic stability , spared the use of isoflurane and reduced the requirement of postoperative analgesia so as to smoother the way to recovery in patients undergoing LC", "BACKGROUND Little is known about physician attitudes , goals , or satisfaction regarding acute postoperative and cancer pain management . OBJECTIVES To provide quantitative data regarding the status of acute postoperative and cancer pain management by Michigan physicians . To measure physician confidence , preference , and satisfaction as well as identify their pain care goals for acute postoperative and cancer pain management . To evaluate variability in acute postoperative and cancer pain decision making based upon physician demographic characteristics , knowledge , and attitudes . RESEARCH DESIGN A cross-sectional survey , which included two cancer and three acute postoperative pain vignettes . SUBJECTS A r and omly-selected sample of three hundred sixty-eight licensed Michigan physicians who provide clinical care for acute postoperative and cancer pain patients . RESULTS The majority of respondents ( > 50 % ) reported providing acute postoperative pain care frequently , while a minority ( 75 % ) reported goals of at least adequate pain relief without distress for both acute postoperative and cancer pain . Physicians more frequently chose the optimal pain management response for men following prostatectomy ( 56.2 % ) than for women following myomectomy ( 42 % ) . They also chose the optimal response for metastatic prostate cancer more frequently ( 16.3 % ) than for metastatic breast cancer pain management ( 10.7 % ) . CONCLUSION These data highlight physician variability in acute postoperative and cancer pain management decision making . Further study of the physician variable is necessary to improve the management of acute postoperative and cancer pain", "After laparoscopic cholecystectomy , CO2 remains within the peritoneal cavity , commonly causing pain . This prospect i ve r and omized study was performed to determine the efficacy of intraperitoneal normal saline and bupivacaine infusion on postoperative pain after laparoscopic cholecystectomy . Three hundred patients were r and omly assigned to one of six groups of 50 patients each . Group A patients served as controls . In group B patients , normal saline was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated . After suction , a subhepatic closed drain was left for 24 h. In group C patients , bupivacaine 1.5 mg/kg in solution 2.5 mg/ml , minus 15 ml of this solution , which was infiltrated in the trocar wounds , was infused under the right hemidiaphragm at the end of the cholecystectomy . In group D patients , bupivacaine was given as in group C , but a subhepatic drain was left for 24 h. In group E patients , normal saline was used as in group B plus bupivacaine as in group C. Group F patients were treated as in group E , but a subhepatic drain was left for 24 h. In all groups , 15 ml of a 2.5 mg/ml bupivacaine solution was infiltrated in the trocar wounds . Postoperatively , analgesic medication usage , nausea , vomiting , and pain scores were recorded at 2 , 6 , 12 , 24 , 36 , 48 , and 72 h. Postoperative pain was reduced significantly in the patients of the treatment groups vs. the controls . Between treatment groups , patients in groups B , E , and F had the best results , while those in groups C and D had significantly greater pain than those in groups B , E , and F. It is concluded that postoperative pain after laparoscopic cholecystectomy can be significantly reduced by intraperitoneal normal saline infusion subdiaphragmatically and after its postdeflation suction , bupivacaine infusion in the same area , or without bupivacaine in case a subhepatic drainage has been needed", "The purpose of this study was to examine the effects of interpleural bupivacaine on analgesia and ventilatory capacity after cholecystectomy . Forty-two patients undergoing elective cholecystectomy were r and omly assigned to two groups : one to receive interpleural administration of bupivacaine-adrenaline mixture ( Croup 1 = 22 patients ) and the other st and ard administration of intramuscular meperidine ( Group 2 = 20 patients ) for postoperative pain relief . The intensity of pain was evaluated by a visual analogue scale ( VAS ) preoperatively as well as at 2 , 8 , 24 and 48 hr postoperatively . At the same time , FVC and FEV1.0 measurements were obtained for all patients . The group given interpleural bupivacaine had better pain relief withmean VAS of 0.6 ± 0.9 ( mean ± SD ) 1.1 ± 1.4 , 0.6 ± 0.9 and 0.8 ± 1.2 compared with 5.2 ± 2.2 . 5.8 ± 2.7 . 5.5 ± 2.2 and 4.5 ± 1.8 for patients receiving meperidine ( P larger FVC and FEV than those in Group 2 : FVC 22 ± 14.5 per cent vs 32 ± 15.2 per cent ( P better pain relief with greater ventilatory capacity than a st and ard analgesic regimen in the first two days after cholecystectomy . RésuméLe but de cet étude clinique était d’examiner les effets de l’administration interpleurale de bupivacaine sur l’analgésie et les fonctions ventilatoires chez des patients opérés de cholécystectomie . Quarante-deux patients admis pour une cholécystectomie élective ont été distribués au hasard en deux groupes . Le Groupe 1 a reçu de la bupivacaine interpleurale ( 22 patients ) et le Groupe 2 a reçu du démérol IM ( 20 patients ) . La qualité de l’analgésie était mesurée à l’aide d’une échelle visuelle analogue ( VAS ) et des tests de fonctions pulmonaires ( CV et VEMS ) étaient faits aux temps suivants : avant l’intervention et 2 , 8 , 24 et 48 hre après l’intervention . Une radiographie pulmonaire était faite à la salle de réveil pour tous les patients du Groupe 1 . Le Groupe 1 était mieux soulagé tel qu’en témoigne la VAS en post-opératoire : Groupe 1:0,6 ± 0,9(± SD ) , 1,1 ± 1,4 , 0,6 ±0,9 et 0,8 ± 1,2 ; Groupe 2:5,2 ± 2,2 , 5,8 ± 2,7 , 5.5 ± 2,2 et 4 , 5 ± 1.8(P fonctions ventilatoires ont été mieux préservées chez les patients recevant la bupivacaine interpleurale tel que démontré par les réductions de la CV ( 22 ± 14.5 pour cent ) et du VEMS ( 25 ± 15,5 pour cent ) observés dans ce groupe comparé au Groupe 2 ( diminution de la CV de 32 ± 15.2 pour cent et VEMS de 38 ± 14,8 pour cent ) ( P de pneumothorax . Nous concluons que la bupivacaine interpleurale est une technique puissante d’analgésie , qu’elle préserve mieux la fonction pulmonaire que la mépéridine IM et que le cathéter peut être installé par voie percutanée en toute sécurité", "Purpose To determine whetherthe continuous low thoracic extradural administration of the same dose of lidocaine at low concentration with a high infusion rate or at high concentration with a low infusion rate in combination with a fixed dose of buprenorphine ( 0.4 ing·day−1 ) modifies postoperative pain relief . Methods Twenty-eight patients undergoing elective upper abdominal surgery were r and omly allocated to one of two groups to receive lidocaine 2 % — buprenorphine at a rate of 6.3 ml · hr−1 ( 2 % group , n = 13 ) or lidocaine 6 % — buprenorphine at a rate of 2.1 ml · hr−1 ( 6 % group , n = 15 ) . During suture of the peritoneum , mepivacaine 2 % ( 8 ml ) with 0.1 mg ( 0.5 ml ) buprenorphine was infused extradurally . After extubation , the continuous extradural infusion was initiated . Patients were assessed for the level of analgesia with the 10 cm VAS score at rest and with the Prince Henry Pain Scale ( PHPS ) at 3 , 6 , 9 , 12 , 18 , and 24 hr postoperatively . Results The visual analogue scale ( VAS ) scores at rest did not differ between the two groups except at 18 hr after surgery . The Prince Henry Pain Scale ( PHPS ) scores were not different between the two groups post-operatively . Conclusion There was no difference in analgesia produced by the continuous extradural infusion of lidocaine 2 % — buprenorphine at a rate of 6.3 ml · hr−1 and that of lidocaine 6 % — buprenorphine at a rate of 2.1 ml · hr−1 following upper abdominal surgery . RésuméObjectifDéterminer si la perfusion épidurale thoracique basse d’une même dose de lidocaïne à basse concentration avec un débit élevé de perfusion ou une haute concentration avec un débit faible de perfusion en association avec une dose fixe de buprénorphine ( 0,4 mg · j−1 ) modifie le soulagement de la douleur . MéthodesVingt-huit patients programmés pour une chirurgie non urgente de l’étage supérieur de l’abdomen participaient à l’étude . Ils étaient répartis aléatoirement en deux groupes do nt l’un recevait lidocaïne 2 % —buprénorphine à la vitesse de 6,3 ml · h−1 ( groupe 2 % = 13 ) l’autre lidocaïne 6 % — buprénorphine ( groupe 6 % = 15 ) à la vitesse de 2,1 ml · h−1 . Au moment de la fermeture du péritoine , on injectait en épidural de la mépivacaïne à 2 % ( 8 ml ) avec 0,1 mg ( 0,5 ) de buprénorphine . Après l’extubation , on débutait la perfusion épidurale continue . Le niveau d’analgésie des patients était évalué à 3 , 6 , 9 , 12 , 18 et 24 heures en post-opératoire au moyen de l’EVA de 10 cm pour la douleur au repos et avec le Prince Henry Pain Scale (PHPS).RésultatsLes scores sur l’ÉVA au repos ne différaient pas entre les groupes excepté 18 hres après l’intervention . Le PHPS n’était différent en aucun moment de la période postopératoire Conclusion Après une chirurgie abdominale , l’analgésie produite par la perfusion épidurale de lidocaïne 2 % — buprénorphine au débit de 6,3 ml·h−1 était la même que celle produite par la lidocaïne 6 % — buprénorphine au débit de 2,1 ml·h−1", "The analgesia provided in the postoperative period by three regimens commonly used in our private anaesthetic practice were compared in a double-blind study of one hundred and thirty-seven women presenting for day-case laparoscopic procedures . After r and om allocation into three groups , all patients were similarly anaesthetized and then received both a rectal suppository and an IM injection . Group P received two placebos , Group I had an indomethacin suppository 100 mg , and Group K an IM injection of ketorolac 30 mg . The trial showed a statistically significant reduction in pain at 180 minutes postoperatively in the group receiving ketorolac ( visual analog pain score of 13.8 v 21.7 ) . The parenterally administered ketorolac may be a useful analgesic supplement in these patients . However the trial was aborted following the appearance in the literature of case reports of postoperative renal failure . Further investigation of the efficacy and side-effect profile of reduced doses may be warranted", "This study was undertaken to determine whether epidural analgesia has any benefit for post-operative pain relief in patients undergoing laparoscopic cholecystectomy . Patients were r and omly assigned to receive post-operative epidural analgesia with a morphine-bupivacaine combination ( Group A , n = 22 ) or placebo ( saline ) ( Group B , n = 22 ) . The same st and ard general anaesthetic technique , which consists of nitrous oxide and isoflurane in oxygen was used . Analgesia was assessed using visual analogue pain scores ( 0 - 10 cm ) . The evaluation was carried out 24 and 48 h post-operatively . At 24 h after anaesthesia , pain scores in Group A ( 2.3 + /- 1.2 ) were lower than those in Group B ( 4.4 + /- 1.5 ) ( P no difference in scores was observed between the two groups . In conclusion , epidural analgesia with a morphine-bupivacaine combination improves pain relief during the first 24 h following laparoscopic cholecystectomy", "Thirty-seven women undergoing elective cholecystectomy were r and omised into two groups , receiving either lumbar epidural morphine ( group L ) or epidural morphine via the thoracic route ( group T ) . The effect on pain relief was assessed by a visual analogue scale and included both resting pain and ‘ provoked ’ pain . Respiratory parameters ( PEF , FEVI and FVC ) were also studied . The patients were investigated preoperatively , and 4 , 6 , 12 and 24 hours after the start of surgery . No significant difference was observed between the groups concerning pain relief or respiratory performance . We conclude that after cholecystectomy lumbar epidural morphine is as effective as thoracic epidural morphine in relieving postoperative pain", "Twenty‐five patients who had undergone elective cholecystectomy were prospect ively r and omized to receive via an interpleural catheter either a continuous infusion of 0.25 % bupivacaine at 0.125 mL·kg−1·h−1 ( n = 13 ) or repeated bolus injections ( n = 22 ) of 0.5 % bupivacaine with epinephrine 1:200,000 at 0.4 mL/kg every sixth hour . Adequacy of pain relief was measured by the amount of patient‐controlled analgesia morphine required postoperatively and by patient scores on a visual analog scale obtained every sixth hour . Two venous blood sample s for measurements of serum bupivacaine levels were obtained from patients in the continuous group at hours 6 and 24 ; four blood sample s were obtained from patients in the bolus group , both immediately before and 30 min after injections at hours 6 and 24 . Among the patients receiving the bolus injections , morphine was required 62 ± 15 ( SEM ) times over the 24-h study period with total morphine dosage averaging 30 ± 15 mg . Corresponding values for patients in the continuous group were 35 ± 10 times and 23 ± 5 mg of morphine . The difference was not , however , statistically significant , but when activity during the 2-h time periods immediately before reinjection ere examined , patients in the bolus group required and received significantly more morphine than did those in the continuous group ( P had visual analog scale scores that averaged 2.9 ± 0.6 over the 24-h study period . Patients within the bolus group had visual analog scale scores before and again 30 min after injection that averaged 5.8 ± 0.8 arid 1.8 ± 0.5 , respectively ( P increased in both groups between the sixth and 24th hour measurements ; the average postinjection bupivacaine levels were significantly higher ( P The bupivacaine level rose to 3.2 ± 0.4 μg/mL 30 min after the bolus injection at hour 24 . In summary , continuous interpleural infusion of 0.25 % bupivacaine provides safer and more effective postoperative pain relief after cholecystectomy than does intermittent interpleural injection of 0.5 % bupivacaine with epinephrine every 6", "BACKGROUND In a l and mark hypothesis-generating study , Todd et al found that a difference of approximately 13 mm ( 95 % confidence interval [ CI ] 10 to 17 mm ) on a visual analog scale ( VAS ) represented the minimum change in acute pain that was clinical ly significant in a cohort of trauma patients . STUDY OBJECTIVE We test the hypothesis that the minimum clinical ly significant change in pain as measured by the VAS in an independent , more heterogeneous validation cohort is approximately 13 mm . METHODS This was a prospect i ve , observational cohort study of adults presenting to 2 urban emergency departments with pain . At 30-minute intervals during a 2-hour period , patients marked a VAS and were asked if their pain was \" much less , \" \" a little less , \" \" about the same , \" \" a little more , \" or \" much more . \" All data were obtained without reference to prior VAS scores . The minimum clinical ly significant change in pain was defined a priori as the difference in millimeters between the current and immediately preceding VAS scores when \" a little more \" or \" a little less pain \" was reported . RESULTS Ninety-six patients enrolled in the study , providing 332 paired pain measurements . There were 141 paired measurements design ated by patients as \" a little less \" or \" a little more \" pain . The mean clinical ly significant difference between consecutive ratings of pain in the combined \" little less \" or \" little more \" groups was 13 mm ( 95 % CI 10 to 16 mm ) . The difference between this finding and that of Todd et al was 0 mm ( 95 % CI -4 to 4 mm ) . CONCLUSION These data are virtually identical to previous findings indicating that a difference of 13 mm on a VAS represents , on average , the minimum change in acute pain that is clinical ly significant", "Purpose : To determine the effect of 90 mg dextromethorphan (DM)po vs placebo 90 min preoperatively , on the immediate and delayed postoperative course . Methods : Thirty patients undergoing laparoscopic cholecystectomy or inguinal hernioplasty under general anesthesia were studied . Half ( DM ) received 90 mg dextromethorphan and half received placebo 90 min before anesthesia . Intravenous Patient Controlled Aanalgesia with morphine was available for two hours within a six-hour observation period ; 75 mg diclofenacim prn was given later in PACU and on-ward ( 24 hr ) . Pain was assessed using the visual analogue scales . Thermal thresholds for cold and hot sensation and for pain ( by limit method ) were evaluated at the site of skin incision ( primary - ) and distantly ( secondary hyperalgesia ) . Von Frey filaments were applied testing touch sensation . Sedation level and morphine consumption were also assessed in PACU . Results : Demographic , surgical and perioperative parameters were similar ; no untoward effects were encountered . Pain intensity and sedation were lower , and the feeling of well-being was greater , in the DM patients : onevs five ( median ) , twovs five , fivevs two , respectively , P absence of primary and secondary hyperalgesia only in the DM patients ; von Frey filaments induced similar pain sensation in both groups . Mean morphine/group , morphine/weight and diclofenac injection rates were ∼55 % lower in the DM group : 2.1±1.2 (SD)vs 4.7±2.3 , 0.03±0.02vs 0.07±0.03 , 1.0±0.3vs 2.4±0.2 , respectively , P placebo , DM enabled reduction of postoperative analgesics consumption , improved well-being , and reduced sedation , pain intensity and primary and secondary thermal hyperalgesia . RésuméObjectif : Déterminer l’effet de 90 mg de dextrométhorphane (DM)po vs un placebo , administrés 90 min avant l’opération , sur l’évolution postopératoire immédiate et tardive . Méthode : L’étude a porté sur 30 patients devant subir une cholécystectomie laparoscopique ou un hernioplastie inguinale . La moitié a reçu 90 mg de dextrométhorphane et l’autre moitié , un placebo , 90 min avant le début de l’anesthésie générale . La morphine , en qualité d’analgésie intraveineuse autocontrôlée , a été disponible pendant deux heures sur une période d’observation de six heures ; 75 mg de diclofénacim prn ont été administrés plus tard à la salle de réveil et à la chambre ( 24 h ) . La douleur a été évalué grâce à l’échelle visuelle analogique . Les seuils thermiques de sensation au froid et à la chaleur ainsi qu’à la douleur ( selon une méthode du seuil différentiel ) ont été évalués au site de l’incision cutanée ( hyperalgésie primaire ) et à distance ( hyperalgésie secondaire ) . Des filaments von Frey ont été appliqués pour tester le toucher . On a aussi évalué , à la salle de réveil , le niveau de sédation et la consommation de morphine . Résultats : Les paramètres démographiques , chirurgicaux et périopératoires ont été similaires : aucun effet indésirable n’a été noté . L’intensité de la douleur et de la sédation a été plus faible , et le confort meilleur , chez les patients du groupe DM : unvs cinq ( médiane ) , deuxvs cinq , cinqvs deux , respectivement , P de sensibilité thermique a révélé l’absence d’hyperalgésie primaire et secondaire chez les patients du groupe DM seulement ; les filaments von Frey ont induit une sensation de douleur similaire chez les patients des deux groupes . La consommation moyenne de morphine selon le groupe et selon le poids des patients ainsi que les taux d’injection de diclofénac ont été de ∼55 % plus bas dans le groupe DM : 2,1±1,2 ( écart type)vs 4,7±2,3 ; 0,03±0,02vs 0,07±0,03 ; 1,0±0,3vs 2,4±0,2 , respectivement , P placebo , le DM a permis de réduire la consommation d’analgésiques postopératoires , a amélioré le confort et a réduit la sédation , l’intensité de la douleur et l’hyperalgésie thermique primaire et secondaire", "This r and omized double-blind placebo-controlled study was design ed to evaluate the effects on postoperative pain of the local anesthetic , 0.5 % bupivacaine with epinephrine , sprayed hepatodiaphragmatically under the surgeon 's direct view during laparoscopic cholecystectomy . Metabolic endocrine responses to surgery ( glucose and cortisol ) and nonsteroidal anti-inflammatory drug requirements were investigated , as well as the presence of nausea , vomiting , and sweating . Local anesthetics or placebo solutions were given as follows . Immediately following the creation of a pneumoperitoneum , surgeons sprayed the first 20 mL of solution ( S1 ) , and an additional 20 mL of solution ( S2 ) was sprayed at the end of the operation . Patients were classified into three groups ( 14 patients per group ) . Group A received 20 mL of saline during both S1 and S2 , group B received 20 mL of saline during S1 and 20 mL of bupivacaine during S2 , and group C received 20 mL of bupivacaine during both S1 and S2 . The degree of postoperative pain was assessed using the visual analogue scale ( VAS ) and the verbal rating scale ( VRS ) on arrival in the recovery room and subsequently at time intervals of 4 h , 8 h , 12 h , and 24 h. The results of this study indicate a significant decrease of postoperative pain in patients treated with local anesthetic . VAS and VRS pain scores , as well as respiratory rate and analgesic requirements , were significantly lower in group C. The postoperative plasma cortisol level in group C was significantly lower than in groups A and", "Purpose : To evaluate the effects of tramadol administration at wound closure on postoperative pain and analgesic requirements in patients undergoing laparoscopic cholecystectomy . Methods : In a prospect i ve , r and omized , double-blind study 80 patients were allocated into two groups ( n=40 in each ) to receive either 200 mg tramadol or placeboiv at the time of wound closure . Prostoperatively , all patients received tramadol from a patient-controlled analgesia ( PCA ) device . Pain , analgesic consumption , vital signs and side effects were recorded postoperatively for 24 hr . Results : Administration of 200 mg tramadol at the time of wound closure was associated with a short-lived ( 60 min ) reduction in pain scores and PCA consumption compared with placebo . Although the time to first request for analgesia after surgery was longer in patients who received tramadol at wound closure , there was no difference between the two groups with respect to pain scores or to the requirements of postoperative analgesia over the next 23 hr . The cumulative PCA consumption of tramadol in 24 hr was 139.4±108 and 102.4±106 mg in the placebo and tramadol groups , respectively ( P=0.06 ) . Conclusions : Wound closure administration of 200 mg tramadol had a short-lived ( 60 min ) analgesic effect but did not affect the long-term pain scores or analgesic requirements after laparoscopic cholecystectomy . RésuméObjectif : Évaluer les effects de l’administration de tramadol , lors de la suture de la plaie chirurgicale , sur la douleur postopératoire et les besoins analgésiques chez des patients qui subissent une cholécystectomie laparoscopique . Méthode : Il s’agit d’une étude prospect i ve , r and omisée et en double aveugle auprès de 80 patients , répartis en deux groupes de 40 , qui ont reçu 200 mg de tramadol ou un placebo iv au moment de la suture de la plaie . Après l’opération , tous les patients ont reçu du tramadol sous forme d’analgésie contrôlée par le patient ( ACP ) . La douleur , la consommation d’analésique , les signes vitaux et les effects secondaires ont été enregistrés pendent 24 h après l’intervention . Résultats : L’administration de 200 mg de tramadol , comparé au placebo , lors de la fermeture cutanée , a été associée à une brève ( 60 min ) diminution des scores de douleur et de la consommation d’ACP . Même si le temps écoulé avant la première dem and e d’analgésie postopératoire a été plus long chez les patients qui ont reçu du tramadol au moment de la suture de la plaie , il n’y a pas eu de différence intergroupe quant aux seuils de douleur ou aux besoins d’analgésie postopératoire pendant les 23 h suivantes . La consommation totale de tramadol en ACP pendant 24 h a été de 139,4±108 et 102,4±106 mg dans les groupes placebo et tramadol , respectivement ( P=0,06 ) . Conclusion : L’administration de 200 mg de tramadol lors de la suture de la plaie chirurgicale a un effect analgésique de courte durée ( 60 min ) , mais ne modifie pas les scores de douleur ou les besoins analgésiques à long terme qui suivent la cholécystectomie laparoscopique", "The effect of interpleural analgesia on postoperative hospital course was analyzed in a prospect i ve r and omized study of patients undergoing cholecystectomy . Control patients were treated in the st and ard manner with systemic narcotics alone ; catheter patients had an interpleural catheter placed at the end of surgery and , in addition , could receive systemic narcotics if necessary . The catheter group received interpleural 0.5 % bupivacaine with epinephrine every six hours for a total of four injections . Thirteen patients were in each group . Pain score , pulmonary function and narcotic requirement were measured over the first postoperative day . Catheter patients had a lower average pain score ( visual analog scale ( VAS ) , 3.6 versus 5.2 ) , decreased narcotic requirement in the recovery room and improved oxygen saturation ( 96 % versus 93 % ) . However , there was no statistical difference in amount of morphine ( catheter , 25 ± 14 mg ; control , 31 ± 15 mg ) , number of narcotic injections ( catheter , 3.8 ± 1.5 ; control , 3.5 ± 1.5 ) , forced vital capacity ( catheter , 44 % preoperative control , 41 % preoperative ) , recovery room time ( catheter , 129 ± 54 minutes , control , 117 ± 39 minutes ) or total hospital stay ( catheter , 4.1 ± 0.9 days ; control , 3.7 ± 0.8 days ) . Analysis of hourly VAS scores following a bolus indicated that the analgesia disappeared within approximately four hours . The mean time to a request for narcotic following a bolus was 4.2 hours ( excluding 17 of a potential total of 52 instances when narcotic was not requested at all ) . Therefore , the duration of pain relief for subcostal incisions using interpleural 0.5 % bupivacaine is approximately four hours . In conclusion , while there are some advantages conferred to patients treated with the intrapleural catheter , it would appear that a bolus regimen more frequent than every six hours would be necessary to maximize any benefit", "It is a common clinical observation that postoperative pain may be resistant to morphine . The analgesic potentials of ketamine have also been well documented . In this study , we evaluated the effects of postoperative coadministration of small doses of ketamine and morphine on pain intensity , Spo2 , and subjectively rated variables in surgical patients who underwent st and ardized general anesthesia and complained of pain ( ≥6 of 10 on a visual analog scale [ VAS ] ) despite > 0.1 mg/kg of IV morphine administration within 30 min . Patients r and omly received up to three boluses of 30 & mgr;g/kg of morphine plus saline ( MS;n = 114 ) or 15 & mgr;g/kg of morphine plus 250 & mgr;g/kg of ketamine ( MK;n = 131 ) within 10 min in a double-blinded manner . The MS group ’s pain VAS scores were 5.5 ± 1.18 and 3.8 ± 0.9 after 10 and 120 min , respectively , after 2.52 ± 0.56 injections , versus the MK group ’s VAS scores of 2.94 ± 1.28 and 1.47 ± 0.65 , respectively ( P The 10-min level of wakefulness ( 1–10 VAS ) in the MS group was significantly ( P ± 1.19 ) . Spo2 decreased by 0.26 % in the MS group but increased by 1.71 % in the MK patients at the 10-min time point ( P ) experienced nausea/vomiting ; nine MK patients sustained a 2-min light-headed sensation , and one patient had a weird dream after the second drug injection", "We investigated , in a double-blind study , the effects of intraperitoneal local anesthetics during laparoscopic cholecystectomy . In Part A of the study 30 patients received 50 mL saline 0.9 % ( A 0 ) , bupivacaine 0.125 % ( A 125 ) , or bupivacaine 0.25 % ( A 25 ) intraperitoneally at the end of surgery . Mean maximum plasma concentrations of bupivacaine reached 0.48 mg/L ( range 0.15 - 0.90 mg/L ) in Group A 125 and 1.0 mg/L ( 0.35 - 2.10 mg/L ) in Group A 25 within 15 min ( range , 5 - 30 min ) . There was no significant difference in pain scores or opioid consumption ( patient-controlled analgesia with piritramid ) : 24 , 28 , and 13 mg/24 h among the study groups , respectively ( not significant ) . Postoperative respiratory function deteriorated in comparison to preoperative values in all study groups , but the forced vital capacity was significantly more impaired in Group A.25 . In Part B , 24 patients received placebo ( B 0 ) or bupivacaine 0.25 % ( B 25 ) . Postoperative hypoxemic periods ( oxygen saturation bupivacaine during laparoscopic cholecystectomy . ( Anesth Analg 1995;81:967 - 72", "This prospect i ve , double-blind , r and omized , and placebo-controlled study evaluates the effectiveness of intraperitoneal bupivacaine in decreasing the length of stay for elective laparoscopic cholecystectomy patients . Seventy-seven patients undergoing elective laparoscopic cholecystectomy before noon at a single institution and by a single group of surgeons were entered into the study . The pharmacy r and omly assigned each patient to one of four study groups ( control , predissection , postdissection , and both ) . Two syringes ( A and B ) containing 15 cm3 of either normal saline or 0.5 per cent bupivacaine were sent with the patient to surgery . Syringe A was sprayed over the perihepatic area before any dissection , and B was sprayed over the perihepatic area just before port removal . Preoperative , intraoperative , and postoperative data were collected . Sixty-six patients completed the study : control , 14 ; predissection , 18 ; postdissection , 15 ; and both , 19 . There was no statistical difference between the predissection , postdissection , and both groups regarding same-day discharge . Therefore , these groups were combined for comparison against the control group . The study found that patients receiving bupivacaine at any time during the surgery were more likely to go home the same day as their procedure ( 79 % vs 43 % , respectively : P < 0.02 )", "OBJECTIVES To determine if intraoperative instillation of bupivacaine would decrease early postoperative pain after laparoscopic cholecystectomy , if the patients would consequently require less narcotic postoperatively and if such patients would elect to be discharged on the day of operation if given the choice . DESIGN Double-blind , r and omized , controlled trial . SETTING A tertiary care hospital in Hamilton , Ont . PATIENTS Fifty patients underwent laparoscopic cholecystectomy . Day-surgery patients had the choice of staying overnight for discharge the following day . They were compared with a control group of 47 patients who had laparoscopic cholecystectomy but did not receive bupivacaine . INTERVENTION Instillation of 20 mL of 0.5 % bupivacaine with epinephrine into laparoscopic cholecystectomy port sites intraoperatively before closure . MAIN OUTCOME MEASURES Visual analogue scale ( VAS ) pain scores assessed 4 times postoperatively , the choice of patients to leave hospital the same day or to remain in the hospital overnight ; the level of postoperative narcotic usage . MAIN RESULTS Mean VAS pain scores ( range 0 [ no pain ] to 5 [ severe pain ] ) at less than 2 hours and at 6 hours after surgery were 2.9 and 2.9 , respectively , in the bupivacaine group compared with 4.5 and 4.0 , respectively , in the control group ( p = 0.001 and 0.025 ) . VAS scores at 10 hours postoperatively and the next morning did not differ between the groups . More patients in the bupivacaine group elected to go home on the day of surgery ( p = 0.034 ) . Narcotic usage was not significantly different . CONCLUSION Instillation of bupivacaine into port sites should be st and ard practice for elective laparoscopic cholecystectomy", "The aims of this study were to see if laparoscopic cholecystectomy is associated with a similar postoperative pain pattern to gynaecological laparoscopy and to see whether the use of a suprahepatic suction drain makes recovery from laparoscopic cholecystectomy more comfortable . After routine laparoscopic cholecystectomy and insertion of a suprahepatic suction drain , patients were r and omized to suction or no suction on the drain . The time course of the severity of wound , abdominal and shoulder tip pain was assessed by visual analogue scales administered in the morning and afternoon of the first 3 postoperative days . The control group had a high incidence of shoulder tip pain similar to that after gynaecological laparoscopy . Patients in the treatment group reported significantly less shoulder tip pain than the control group ( O.R. 0.16 , 95 % CI , 0.06 - 0.40 ) . There was a tendency for the treatment group to report reduced abdominal and , to a lesser extent , wound pain . The authors recommend suprahepatic suction as a simple and more effective way to improve patient comfort after laparoscopic cholecystectomy", "Epidural narcotics has been shown to produce profound and long-lasting analgesia . It has been suggested that lipid-soluble narcotics such as fentanyl , because of their short transit time in the CSF , are less likely to be associated with delayed respiratory depression and side effects . We tried to combine low concentrations of fentanyl with bupivacaine to minimize side effects and to see if synergistic effect existed . Forty ASA physical status I or II patients who present for cholecystectomy were included in the trial . Before surgery a thoracic epidural catheter was inserted and pain control began when patients became fully awake and complained of pain in the recovery room after surgery . Patients were r and omized in a double-blind fashion to one of four groups . Patients in group I were given epidural infusions of fentanyl 0.001 % ; patients in group 2 received fentanyl 0.001 % mixed with bupivacaine 0.1 % ; patients in group 3 received fentanyl 0.0005 % ; patients in group 4 received fentanyl 0.0005 % mixed with bupivacaine 0.1 % . A continuous epidural infusion of these drugs began at a rate of 10 mL/h after a 5-mL bolus of the solution . Pain relief was assessed with visual analogue pain scale . Respiratory rates , vital signs , and mental status were assessed hourly . Except the group 3 , the degree of analgesia achieved was similarly satisfactory in all other groups . There was no respiratory depression developed in either group . Motor block was minimal or absent in all groups . The incidence of nausea and pruritus was significant less in group 3 and group 4 . In conclusion , the continuous infusion of dilute bupivacaine with fentanyl provides synergistic analgesia with minimal side effects", "Background A controversy exists over the effectiveness and clinical value of preemptive analgesia . Additional studies are needed to define the optimum intensity , duration , and timing of analgesia relative to incision and surgery . Methods One hundred twenty patients undergoing laparoscopic cholecystectomy under general anesthesia plus topical peritoneal local anesthetic or saline were studied . Local anesthetic ( 0.5 % bupivacaine with epinephrine ) or placebo solutions were given as follows : immediately after the creation of a pneumoperitoneum ( blocking before surgery ) , and at the end of the operation ( blocking after surgery ) . Patients were r and omly assigned to one of four groups of 30 patients each . Group A ( placebo ) received 20 ml 0.9 % saline both before and after surgery , group B received 20 ml 0.9 % saline before surgery and 20 ml local anesthetic after surgery , group C received 20 ml local anesthetic both before and after surgery , group P received 20 ml local anesthetic before and 20 ml 0.9 % saline after surgery . Pain was assessed using a visual analog scale and a verbal rating scale at 0 , 4 , 8 , 12 , and 24 h after surgery . Metabolic endocrine responses ( blood glucose and cortisol concentrations ) and analgesic requirements also were investigated . Results Pain intensity ( visual analog and verbal rating scales ) and analgesic requirements were significantly less in the group receiving bupivacaine after surgery compared to placebo . However , in the groups receiving bupivacaine before surgery , both pain intensity and analgesic consumption were less than in the group receiving bupivacaine only after surgery . Blood glucose and cortisol concentrations 3 h after surgery were significantly less in groups receiving bupivacaine before surgery . Conclusions The results indicate that intraperitoneal local anesthetic blockade administered before or after surgery preempts postoperative pain relative to an untreated placebo-control condition . However , the timing of administration is also important in that postoperative pain intensity and analgesic consumption are both lower among patients treated with local anesthetic before versus after surgery", "BACKGROUND Needlescopic cholecystectomy ( NC ) utilises instruments and ports smaller than 3 mm in diameter compared with the 5 mm ones used in conventional laparoscopic cholecystectomy ( LC ) . Post-operative pain control and recovery has been thought to be superior in NC , when compared with historical controls with LC , but has not been proven in a prospect i ve fashion . PATIENTS AND METHODS A prospect i ve r and omised trial of NC versus LC for patients with symptomatic gallstone disease , with st and ardisation of post-operative analgesia and daily assessment of post-operative pain , using a 5-point visual analogue scale . RESULTS There were 64 eligible patients r and omised into NC ( 28 ) and LC ( 36 ) . Four patients who had NC were converted to LC due to technical problems . Another three and six patients from the NC and LC groups , respectively , had conversion to open surgery . Post-operative pain scores were low in both groups . Mean pain scores for those with successful NC and LC were : 1.24 versus 1.43 for the day of operation ( P = 0.49 ) , 0.86 versus 0.83 for the first day post-operatively ( P = 0.92 ) and 0.75 versus 0.81 for the second post-operative day ( P = 0.87 ) . The mean number of intra-muscular analgesic injections required were 0.76 versus 0.83 after NC and LC , respectively ( P = 0.93 ) . There were no significant differences between the two groups in the time taken to return to feeding , eating a normal diet and discharge from hospital . CONCLUSION There is no advantage of NC over LC in terms of post-operative pain or recovery . Nevertheless , NC can be performed safely and expediently and has an excellent cosmetic outcome and high patient acceptability", "Abstract Background : We conducted a r and omized controlled trial during laparoscopic cholecystectomy to determine the extent of heat preservation and postoperative pain reduction using humidified carbon dioxide ( CO2 ) gas insufflation instead of st and ard dry insufflation gas . Methods : Forty consecutive patients were r and omized . Twenty patients received humidified CO2 , and 20 control patients received st and ard CO2 insufflation . A sample of 16 patients from each group was evaluated for postoperative pain levels . Results : No adverse effects from the humidification of insufflated gas were observed . There was no significant difference in core body temperature between the two groups for this brief operation . Pain , as assessed by the Analogue Pain Score ( APS ) was significantly less for the group with humidified gas insufflation than for the control group at 6 h postoperatively as well as on the 1st , 2nd , and 3rd postoperative day and at follow-up 10 days after the operation . In the humidified group , the mean time to return to normal activities was significantly less—5.9 days , as compared to 10.9 days in the control group . Conclusions : The use of humidified insufflation gas reduces postoperative pain following laparoscopic cholecystectomy , but except for these relatively brief procedures , the heat-preserving effect of humidified gas insufflation is not significant", "Abstract Background : Prolonged and complex laparoscopic procedures expose patients to large volumes of cool insufflation gas . The aim of this study was to compare the effects of a conventional room temperature carbon dioxide ( CO2 ) pneumoperitoneum with those of a body temperature pneumoperitoneum . Methods : Patients were r and omized to undergo laparoscopic cholecystectomy with a CO2 pneumoperitoneum warmed to either body temperature ( n= 15 ) or room temperature ( n= 15 ) . The physiologic and immunologic effects of warming the gas were examined by measuring peroperative core and intraperitoneal temperatures , peritoneal fluid cytokine concentrations , and postoperative pain . Results : The mean duration of surgery was 32 min in both groups . Core temperature was reduced in the room temperature group ( mean , 0.42 ° C ; p reduction in temperature occurred when the gas was warmed . Greater levels of cytokines were detected in peritoneal fluid from the room temperature insufflation group tumor necrosis factor alpha ( TNF-α ) : mean , 10.9 pg/ml vs. 0.42 , p difference in postoperative pain scores or analgesia consumption between the two groups . Conclusions : The authors conclude that intraoperative cooling can be prevented by warming the insufflation gas , even in short laparoscopic procedures . In addition , warming the insufflation gas leads to a reduced postoperative intraperitoneal cytokine response", "OBJECTIVE : To compare the efficacy and toxicity of three patient-controlled analgesia ( PCA ) morphine regimens . DESIGN : A prospect i ve , r and omized , pilot study of three PCA morphine regimens : ( 1 ) 1 mg with 6-minute lockout ( n=10 ) , ( 2 ) 2 mg with 12-minute lockout ( n=12 ) , and ( 3 ) 2 mg with 20-minute lockout ( n=12 ) . SETTING : Large teaching institution . PARTICIPANTS : Thirty-four patients undergoing cholecystectomy or hysterectomy . MAIN OUTCOME MEASURES : Pain scores ( 0 = no pain , 1 = mild pain , 2 = moderate pain , 3 = severe pain ) , sedation scores , analgesic consumption , and patient attempts ( patient activation of PCA device ) and injections ( doses actually delivered ) were evaluated using analysis of covariance . Distribution of pain and sedation scores and adverse effects were assessed using Fisher 's exact test . RESULTS : Data on 24 patients were evaluable . Six patients withdrew for poor pain control ( 2 in group 1 , 1 in group 2 , and 3 in group 3 ) . Three other patients withdrew because of adverse effects and 1 withdrew because of pump problems . Mean morphine consumption did not differ significantly among the groups . Distribution of pain and sedation scores and the number of patients with nausea were similar across treatment groups . The mean injection to attempt ratio was significantly smaller in group 3 ( 0.71 ± 0.11 ) compared with groups 1 and 2 ( 0.9 ± 0.06 and 0.83 ± 0.09 , respectively ; p=0.001 ) . Adverse events occurred similarly among treatment groups . CONCLUSIONS : No significant differences in the efficacy or toxicity of the three morphine PCA regimens were identified", "Abstract Purpose . The effects of oral administration of clonidine on sympathetic and endocrinological responses were investigated in patients undergoing elective laparoscopic cholecystectomy . Methods . Twenty adult patients were allocated r and omly to the clonidine group ( n = 10 ) or the control group ( n = 10 ) . The control and clonidine groups received placebo on clonidine 4μg·kg−1 orally 2 h before the induction of anesthesia . All patients underwent laparoscopic cholecystectomy under isoflurane anesthesia . The hemodynamic variables were observed perioperatively . Plasma concentrations of cortisol , ACTH , noradrenaline , adrenaline , and dopamine were determined before administration of clonidine or placebo , 2 h after the beginning of the operation , and 3 h after the end of the operation . Results . Systolic and diastolic blood pressures were lower in the clonidine group than in the control group immediately after endotracheal intubation and extubation ( P lower plasma concentrations of noradrenaline 2 h after the beginning of the operation than patients in the control group ( P the plasma concentrations of the other hormones did not differ between groups . Conclusion . Clonidine premedication prevents sympathetic hyperactivity but does not suppress hypothalamo-pituitary-adrenocortical responses in patients undergoing laparoscopic cholecystectomy", "The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery induces cardiovascular , neuroendocrine , and renal changes . Concern about these pathophysiologic changes has led to the introduction of a gasless technique . Fifty consecutive patients with symptomatic gallstones were r and omized to conventional ( CLC ) or gasless laparoscopic cholecystectomy ( GLC ) , with special reference to overall patient satisfaction , technical difficulties , duration of surgery , postoperative pain , and recovery . The overall exposure of the operative field was extremely poor in the GLC group , whereas the duration of surgery , steps involved in the cholecystectomy technique , length of hospital stay , and postoperative pain score did not differ significantly . After discharge , the median time to complete relief of pain tended to be shorter in the gasless group ( 5 days [ range 1 to 15 ] ) vs. the conventional group ( 8 days [ range 1 to 15 ] ) . The period to return to normal activity was shorter in the GLC group ( 6 days [ range 1 to 1.5 ] ) compared to the CLC group ( 8.5 days [ range 1 to 15 ] ) ( P = 0.031 ) . No differences were found in terms of fatigue , dizziness and nausea , and overall satisfaction with the outcome . This study demonstrates a significantly shorter convalescence after laparoscopic cholecystectomy by means of the gasless technique compared to the conventional CO2 technique . Exposure of the operative field was less than optimal using the gasless technique", "Nalbuphine ( 0.3 mgkg−1 ) and buprenorphine ( 2.5 μgkg−1 ) were compared as part of a total intravenous anaesthesia regimen using a propofol infusion in 60 patients undergoing laparoscopic cholecystectomy in a r and omised double‐blind study . Changes in haemodynamic variables greater than 20 % from the baseline were noted . No difference was observed in blood pressure but the heart rate was significantly lower in the buprenorphine group . Intra‐operative bradycardia ( heart rate awareness . Quality of analgesia was similar in both groups . Both drugs provide suitable analgesic supplementation to total intravenous anaesthesia", "BACKGROUND Postoperative shoulder-tip pain ( STP ) frequently occurs following laparoscopic surgery . In an attempt to abrogate this complication we prospect ively evaluated the efficacy of intraoperative irrigation of the diaphragm with bupivacaine . METHODS One hundred and five consecutive patients undergoing laparoscopic surgery were prospect ively r and omized to treatment or control groups . Treatment group ( B , n = 55 ) received irrigation with 10 mL 0.5 % bupivacaine in 500 mL saline and control group ( A , n = 50 ) received an equal volume of normal saline . Each dome of the diaphragm was irrigated with 250 mL of either solution at the end of surgery . Laparoscopic procedures performed included cholecystectomy ( n = 63 ) , Nissen fundoplication ( n = 21 ) , appendicectomy ( n = 7 ) , hernia repair ( n = 4 ) , and diagnostic laparoscopy ( n = 10 ) . Patients ' anesthesia and perioperative analgesia were st and ardized . STP was recorded on a visual analogue pain scale ( VAPS ) in the recovery room immediately following surgery and at 4 , 10 , and 24 hours thereafter . RESULTS The overall incidence of STP in patients undergoing laparoscopic procedures was approximately 24 % . Twenty-one patients ( 42 % ) in the control group and 4 patients ( 7 % ) in the treatment group complained of shoulder pain during the recording period ( P = 0.003 ) . Mean STP scores as recorded on VAPS were significantly lower in the bupivacaine group than in the control group from 4 to 24 hours after surgery ( P Postoperative analgesia requirements were also significantly reduced in those patients receiving bupivacaine irrigation ( P bupivacaine to both hemidiaphragms at the end of surgery significantly reduces both frequency and intensity of STP following laparoscopic procedures thus reducing patient morbidity", "In a double-blind , placebo-controlled clinical trial ( power of 80 % to detect a 30 % reduction in morphine consumption , P tenoxicam 40 mg during laparoscopic cholecystectomy , when compared with placebo , was associated with a significant reduction in consumption of morphine at 6 hours and 12 hours ( P “ rescue ” analgesia with intramuscular morphine in the placebo group during the period of the study . There was no difference between the groups in pain scores , either at rest or on movement , nor in the incidence of nausea and vomiting . No patient in either group suffered a respiratory rate less than 8/min or oversedation at any time , and there were no other adverse effects", "Aim : This study evaluated the pre‐emptive analgesic effect of intravenous ( i.v . ) (R)‐ketamine in laparoscopic cholecystectomy . (R)‐ketamine was used due to the lower incidence of side‐effects", "In a r and omized , double-blind , placebo-controlled study design ed to assess the post-operative analgesic efficacy and cost-effectiveness of ketorolac and diclofenac 60 ASA I and II patients undergoing laparoscopic cholecystectomy were studied . Prior to concluding the operative procedure , an injection ( i.m . ) of an equal volume of either saline 3 mL , ketorolac 60 mg , or diclofenac 75 mg was administered . All patients received intravenous morphine via a patient-controlled analgesia device ( PCA ) . Post-operative pain intensity was assessed hourly for 4 h , by recording visual analogue score ( VAS ) for pain , PCA dem and s and actual morphine administered . PCA dem and s ( mean + /- SD ) were greater in the saline treatment group ( 115 + /- 90 ) when compared with both the ketorolac ( 42 + /- 44 ) and diclofenac groups ( 74 + /- 77 ) . Furthermore , the saline treatment group received significantly ( P PCA morphine compared with both the ketorolac and diclofenac groups ( 12.2 mg + /- 5.0 vs. 8.6 mg + /- 5.2 vs. 8.9 mg + /- 4.8 ) . Improved pain scores were demonstrated in both the ketorolac and diclofenac groups compared with the saline group . PCA dem and s and post-operative morphine requirements were similar in the ketorolac and diclofenac groups . Diclofenac has the added advantage , in our institution , of being 60 % less expensive than ketorolac . We conclude that both ketorolac and diclofenac are effective post-operative analgesic drugs . However , economic considerations may favour diclofenac administration", "An opioid-sparing effect of alpha-trinositol ( D-myo-inositol 1,2,6-trisphosphate ) following cholecystectomy in otherwise healthy patients was suggested by a pilot study . In order to verify this result , pain , pain relief and nausea were studied in patients undergoing elective cholecystectomy by minilaparotomy . The patients were r and omized using double-blind design to receive an intravenous infusion of either alpha-trinositol or sodium chloride ( placebo ) for eight hr after the operation . Pain , pain relief and nausea were evaluated up to 72 hr after surgery using visual analogue scales ( VAS ) . Rescue analgesic medication was registered . As a further measure of pain and /or restrictions caused by pain , peak expiratory flow , walking distance and pressure pain thresholds were assessed . There was no difference between the groups in ratings of pain , pain relief , nausea or amount of analgesic medication given . The mean ratings of pain were significantly higher in the sitting position compared to lying down . Neither pressure pain thresholds , nor the walking distance differed between the patients given alpha-trinositol and placebo , respectively . There were significant reductions of peak expiratory flow and of pressure pain thresholds under both costal margins up to 72 hr after surgery compared to presurgery values . As a conclusion , no analgesic effect of alpha-trinositol at the dosage used was observed in the postoperative patients studied", "Prolonged nerve conduction blockade has been proposed to result from the summed effects of charged and neutral local anaesthetics . Thirty-seven patients were r and omly allocated to receive intravenous patient-controlled analgesia alone or combined with intercostal blockade ( T7-T11 ) with a mixture of 0.45 % bupivacaine and 0.6 % phenol for post-cholecystectomy analgesia . Adequacy of pain relief was measured by patient scores on a 10-cm visual analogue scale and by dose-dem and ratio , amounts of loading dose and total consumption of morphine and also the duration of patient-controlled analgesia in each group . No differences were found between groups in post-operative scores , dose-dem and ratios and loading doses of morphine . However , in the combined treatment group , a significantly lower total consumption of morphine ( P shorter duration of patient-controlled analgesia ( P mean number of unsuccessful dem and s ( P bupivacaine-phenol supplements intravenous patient-controlled analgesia for post-cholecystectomy pain relief", "Trocar injury is one of the most serious and potentially preventable complications of laparoscopic surgery . Use of a blunt rather than a cutting trocar could be expected to lessen the likelihood of this injury . Therefore complications related to laparoscopic port design were studied by comparing conventional cutting trocars with radially exp and ing ( blunt ) trocars . A multicenter , prospect i ve , r and omized clinical trial was conducted in 250 adult patients undergoing elective laparoscopic procedures at tertiary care centers and community hospitals . The patients were r and omly assigned to one of two groups : group C , conventional cutting trocars ; or group S , radially exp and ing trocars . Sixteen surgeons performed 244 elective laparoscopic procedures ; six patients were removed from the study . One hundred nineteen patients were assigned to group S and 125 to group C. The groups were similar with regard to age , sex , and type of procedure . The following data were collected : intraoperative complications related to the trocars , abdominal wall bleeding , visceral or vascular injury , other complications , fascial closure , procedure time , trocar site assessment at 4 and 24 hours postoperatively , and visual analog pain scores at 4 , 8 , 12 , and 24 hours postoperatively . Fascial defects from 10 mm or larger trocars in group C were closed ; the fascial defects in group S were not closed . The trocar sites were checked for incisional hernias at late follow-up . Mean operating time was not different between the two groups ( group S , 92 + -73 minutes ; group C , 100 + -74 minutes ) . There were no episodes of intraoperative cannula site bleeding in group S compared with 16 episodes in 13 patients ( P Postoperative wound complications were fewer in group S ( 13 vs. 23 ; P pain scores were generally lower in group S , the differences were not significant . Only 3 % of the patients in group S had fascial defects of 10 mm or greater that had to be closed . Within a follow-up period of 6 to 18 months , there have been no incisional hernias in either group . This study shows that radially exp and ing trocars are safe and effective , and less likely than conventional trocars to result in intraoperative or postoperative complications . The defects created by the radially exp and ing trocars do not have to be routinely closed", "In this r and omized , double-blinded , placebo-controlled study , we evaluated the effects of preoperative IV parecoxib sodium ( parecoxib ) followed by postoperative oral valdecoxib on length of stay , re source utilization , opioid-related side effects , and patient recovery after elective laparoscopic cholecystectomy . Patients were r and omized to receive a single IV dose of parecoxib 40 mg ( n = 134 ) or placebo ( n = 129 ) 30–45 min before the induction of anesthesia . Six to 12 h after the IV dose , the parecoxib group received a single oral dose of valdecoxib 40 mg , followed by valdecoxib 40 mg once daily on postoperative Days 1–4 and then 40 mg once daily as needed on Days 5–7 . Patients in the parecoxib/valdecoxib group had a shorter length of stay in the postanesthesia care unit ( 78 ± 47 min ) compared with those taking placebo ( 90 ± 49 min ; P the parecoxib/valdecoxib group also had reduced pain intensity and , after discharge , experienced a significant reduction in vomiting in the first 24 h , slept better , returned to normal activity earlier , and expressed greater satisfaction than placebo patients ( P . Preoperative parecoxib followed by postoperative valdecoxib is a valuable adjunct for treating pain and improving patient outcome after laparoscopic cholecystectomy", "Background : Previous work has demonstrated that intraperitoneal ( i.p . ) lidocaine may provide analgesia after laparoscopic cholecystectomy . The aim of this prospect i ve , r and omized , double‐blind study was to compare pain relief , recovery variables , and side effects after i.p . instillation of lidocaine plus tenoxicam given either i.v . or i.p . after laparoscopic cholecystectomy", "To study the possible benefits of N2O pneumoperitoneum , 40 patients scheduled for laparoscopic cholecystectomy for symptomatic cholelithiasis were r and omized into either CO2-induced ( n = 20 ) or N2O-induced ( n = 20 ) pneumoperitoneum groups . The intensity of postoperative pain was assessed by the patients themselves using an visual analogue pain score scale . CO2 insufflation caused respiratory acidosis . The total amount of anesthetic enflurane needed was lower in the N2O than in the CO2 group ( p pain 1 hour ( p Serum cortisol and plasma adrenaline concentrations in the N2O group did not differ from those in the CO2 group . Patients with N2O pneumoperitoneum seem to have less pain without the side effects caused by CO2 . The N2O pneumoperitoneum is a good alternative to the CO2 pneumoperitoneum , especially for prolonged laparoscopic operations in patients with chronic cardiopulmonary diseases", "Anomalous responses to morphine are common in patients with unexplained pain in the upper abdomen after cholecystectomy and may be linked to activation of the sympathetic nervous system . The hypothesis that sympathetic suppression would attenuate anomalous responses to morphine was tested by a r and omized , cross-over trial using a st and ard challenge with morphine , with and without pretreatment with clonidine ( 300 µg orally , 1 h prior to the administration of morphine ) . In 13 of the 15 patients who completed the study , pre-treatment with clonidine decreased plasma concentrations of noradrenaline , dopamine and adrenaline by 56 , 15 and 25 % respectively . This was associated with a significant reduction in morphine-induced pain ( p = 0.02 ) and nausea ( p = 0.04 ) and attenuated increases in plasma aspartate aminotransferase ( AST ) activity ( p = 0.03 ) . Clonidine attenuates anomalous responses to morphine , perhaps through effects on sympathetic nervous activity or plasma concentrations of catecholamines", "A prospect i ve controlled r and omized study was performed on 100 patients undergoing elective laparoscopic cholecystectomy to evaluate the benefit of routine drainage in simple uncomplicated procedures . The 100 patients were r and omized into two groups . Group 1 patients ( n = 50 ) had a drain placed through the epigastric trocar site . The drain was removed before their discharge unless bile or blood was present . Group 2 patients ( n = 50 ) did not have a drain placed . Eleven patients in group 2 ( no drain ) ( 22 % ) were discharged on the same day of surgery ( within 8 h ) , and the remaining 89 patients in both groups were discharged the day after surgery ( within 23 h ) . There were no wound infections or postoperative fever in either group . There were minor but not statistically significant differences between the two groups in postoperative severity and duration of abdominal pain , shoulder pain , and nausea . Furthermore , the two groups were similar in respect to postoperative recovery time and return to work", "Background : Ondansetron has a well documented antiemetic prophylactic effect , whereas in most studies of postoperative nausea and vomiting ( PONV ) , metoclopramide is less efficacious . This can be attributed to the short‐lasting effect of metoclopramide when a low dose is given at the beginning of surgery . We wanted to test a 20‐mg dose of metoclopramide given at the end of surgery , using ondansetron 8 mg as a reference", "Although pain after laparoscopic cholecystectomy is less intense than after open cholecystectomy , some patients still experience considerable discomfort . Furthermore , the characteristics of post-laparoscopy pain differ considerably from those seen after laparotomy . Therefore , we investigated the time course of different pain components after laparoscopic cholecystectomy and the effects of intraperitoneal bupivacaine on these different components . Forty ASA physical status grade I-II patients were r and omly assigned to receive either 80 mL of bupivacaine 0.125 % with epinephrine 1/200,000 ( n = 20 ) or the same volume of saline ( n = 20 ) instilled under the right hemidiaphragm at the end of surgery . Intensity of total pain , visceral pain , parietal pain , and shoulder pain was assessed 1 , 2 , 4 , 6 , 8 , 24 , and 48 h after surgery . Analgesic consumption was also recorded . Patient data were similar in the two groups . In the saline group , visceral pain was significantly more intense than parietal pain at each time point ; visceral and parietal pain were greater than shoulder pain during the first 8 h postoperatively . Intraperitoneal bupivacaine did not significantly affect any of the different components of postoperative pain . Analgesic consumption was similar in the two groups . This study demonstrates that visceral pain accounts for most of the pain experienced after laparoscopic cholecystectomy . Intraperitoneal bupivacaine is not effective for treating any type of pain after laparoscopic cholecystectomy . ( Anesth Analg 1995;81:379 - 84", "The purpose of this r and omized , double-blind , clinical trial was to determine whether intraoperative , intramuscular ( IM ) injections of meperidine or ketorolac would improve postoperative pain relief in patients undergoing elective laparoscopic cholecystectomy . A total of 125 patients were entered into five study groups : 1 ) ( N = 23 ) control placebo ; 2 ) ( N = 31 ) meperidine 100 mg IM intraoperative preprocedure ; 3 ) ( N = 20 ) meperidine 100 mg IM intraoperative postprocedure ; 4 ) ( N = 25 ) ketorolac tromethamine 60 mg IM intraoperative preprocedure ; 5 ) ( N = 26 ) ketorolac tromethamine 60 mg IM postprocedure . All groups were analyzed by comparing the amount of pain medication received in the recovery room , the time until first oral pain medication was requested , the overall amount of pain medication used in the first 24 hours , the percent requiring IM medication , and the pain score ratings from each group . There was decreased pain medication usage in the recovery room in all groups compared to control ( P longer painfree interval than meperidine groups or control . Both Groups 4 and 5 had decreased postoperative narcotic usage . Finally , the analogue pain scores showed that both ketorolac groups had significantly less postoperative pain compared to control , whereas the meperidine groups showed no improvement in postoperative pain relief . Intraoperative ketorolac given preprocedure or postprocedure significantly improved postoperative pain management and facilitated the transition to oral pain medication", "OBJECTIVE To study the effectiveness of intraperitoneal instillation of bupivacaine for postoperative laparoscopic cholecystectomy pain relief , especially specific pain ( visceral pain , shoulder pain and epigastric pain ) . PATIENTS AND METHOD Eighty ASA ( American Society of Anesthesiologists ) 1 and 2 patients were r and omly assigned to receive either 20 ml of 0.5 per cent bupivacaine ( n=39 ) or the same volume of saline ( n=41 ) instilled under direct vision into the hepatodiaphragmatic space , near and above the hepatoduodenal ligament and above the gall bladder bed at the end of surgery . The intensity of visceral pain , shoulder pain and epigastric pain was assessed at 1 , 6 , 24 and 48 h after surgery using a visual analogue scale ( 100 mm VAS ) and verbal rating \" Prince Henry \" pain scale ( VRS ) . The time when analgesia was first required and total analgesic consumption were also recorded . t-test , Chi-square , Mann-Whitney U test and Kaplan-Meier survival analysis were used for statistical analysis . RESULTS Patient data were similar in the two groups except for body weight . There were no statistical differences between the two groups for the time when analgesia was first ' required , VAS , VRS and total analgesic consumption . CONCLUSION In this study , intraperitoneal instillation of bupivacaine does not show any advantage for postoperative analgesia after laparoscopic cholecystectomy", "To determine the influence of the volume of local anesthetic injected for intrapleural analgesia , 40 patients undergoing cholecystectomy were r and omly allocated to two groups of 20 patients each . One group received 40 mL of 0.25 % bupivacaine with epinephrine injected intrapleurally postoperatively . The other group received 20 mL of 0.5 % bupivacaine with epinephrine . The onset time of analgesia was nearly the same in both groups and within 25 min all patients were nearly pain free . Our data demonstrate that 100 mg of bupivacaine with epinephrine elicits effective analgesia after cholecystectomy . There are only minor differences between 20 and 40 mL with regard to pain relief . The authors conclude that the volume of local anesthetic within the range of 20 - 40 mL in an adult has little influence on the extent or duration of intrapleural analgesia", "Aim : This study aim ed to investigate the advantages and disadvantages of LP ( 7 mmHg ) in comparison to SP ( 12 mm Hg ) pneumoperitoneum in a prospect i ve r and omized clinical trial . Material s and Methods : 148 consecutive patients qualified for laparoscopic cholecystectomy ( LC ) due to uncomplicated symptomatic gallstones were r and omized to either SPLC or LPLC . All the procedures were performed by the same experienced team of surgeons . The statistical analysis included sex , mean age , body mass index , ASA grade , operative time , complication rate , conversion rate , postoperative pain assessed by the Visual Analogue Scale of Pain ( VAS ) including the incidence of shoulder-tip pain , postoperative hospital stay , recovery time , and the quality of life ( QOL ) within 7 days following the operation . p conversion to an open procedure nor major complications occurred in either group . The operative time was similar in both groups ( LP 55.7 ± 8.6 min vs SP 51.9 ± 8.3 min ) . The mean postoperative pain score was 6.18 ± 3.48 lower after LP than SPLC and the difference amounted to 22.2 % ( p The incidence of shoulder-tip pain was 2.1 times lower after LP than SPLC ( p within 7 days following the operation was remarkably better after LPLC than after SPLC ( p lower postoperative pain , a lower incidence of shoulder-tip pain , and a better QOL within 5 days following the operation . LP should be used for LC in cases of uncomplicated symptomatic gallstones as a recommended procedure as long as an adequate exposure is obtained with this technique", "One hundred thirty-seven patients participated in a r and omized , double-blind study to determine what effect instillation of fluid at the conclusion of operative laparoscopy has on postoperative postural pain . The first phase examined pain intensity as related to closing pH , operative time and the surgeon . The second phase focused on the absence or presence of postural pain in the fluid and control groups . In phase 1 , there was no significant relationship between pain and duration of surgery , closing pH or surgeon . In phase 2 , 6 of 27 ( 22 % ) patients receiving postoperative fluid instillation experienced postural pain as compared to 19 of 25 ( 76 % ) in the control group ( P frequency of subdiaphragmatic and shoulder pain on sitting or st and ing . This pain is probably produced by traction on the triangular or coronary ligaments of the liver due to loss of the suction effect by the diaphragm", "Purpose The combination of antiemetic drugs could be a solution to prevent severe postoperative nausea and vomiting ( PONV ) . The aim of this r and omized double blind , dose-ranging study was to determine the minimum single effective dose of dexamethasone combined with ondansetron for the prevention of PONV in patients undergoing laparoscopic cholecystectomy . Methods One hundred eighty patients were allocated r and omly to one of six groups to receive saline ( P group ) , ondansetron 4 mg ( O group ) , or ondansetron 4 mg and dexamethasone at doses of 2 mg ( OD2 group ) , 4 mg ( OD4 group ) , 8 mg ( OD8 group ) , and 16 mg ( OD16 group ) . A st and ardized general anesthetic was used . All episodes of PONV during the intervals of zero to six hours , 6–12 hr and 12–24 hr after surgery were evaluated using a numeric scoring system . Mean visual analogue scale pain scores at rest and on movement , the time to first dem and of analgesia , total analgesic consumption in 12 hr epochs , duration of hospital stay , and side effects were recorded . Results The incidence of PONV in the OD8 ( 16 % ) and OD 16 ( 16 % ) groups was lower than in the P 83 % ( P in antiemetic effect between the O , OD2 and OD4 groups and between the OD8 and OD 16 groups . Pain scores , total analgesic consumption , duration of hospital stay and side effects were similar among groups . Conclusion Our results suggest that 8 mg is the minimum dose of dexamethasone that , combined with ondansetron 4 mg will effectively prevent PONV in patients undergoing laparoscopic cholecystectomy . RésuméObjectifLa combinaison de médicaments antiémétiques pourrait être ia solution de ia prévention des nausées et vomissements postopératoires sévères ( NVPO ) . Le but de notre étude de dosage r and omisée et à double insu était de déterminer la dose minimale efficace unique de dexaméthasone qui , combinée à l’ondansétron , puisse prévenir les NVPO chez des patients qui subissent une cholécystectomie laparoscopique . MéthodeCent quatrevingt patients ont été répartis au hasard en six groupes et ont reçu une solution saline ( groupe P ) , 4 mg d’ondansétron ( groupe O ) ou 4 mg d’ondansétron et de la dexaméthasone en doses de 2 mg ( groupe OD2 ) , 4 mg ( groupe OD4 ) , 8 mg ( groupe OD8 ) ou 16 mg ( groupe OD16 ) . Une anesthésie générale normalisée a été utilisée . Tous les épisodes de NVPO survenus entre zéro et six heures , 6–12 h et 12–24 h après l’opération ont été évalués au moyen d’un système de cotation numérique . Les scores de douleur ont été enregistrés avec l’échelle visuelle analogique au repos et lors de mouvement , de même que le moment de la première dem and e d’analgésie , la consommation totale d’analgésique pour la période de 12 h , la durée du séjour hospitalier et les effets secondaires . RésultatsL’incidence de NVPO dans les groupes OD8 ( 16 % ) et OD 16 ( 16 % ) a été plus faible que dans les groupes P ( 83 % , P L’effet antiémétique n’a pas présenté de différence entre les groupes O , OD2 et OD4 et entre les groupes OD8 et OD16 . Les scores de douleur , la consommation totale d’analgésique , la durée du séjour hospitalier et les effets secondaires ont été similaires d’un groupe à l’autre . Conclusion Nos résultats permettent de dire que 8 mg constituent la dose minimale de dexaméthasone qui , combinée à 4 mg d’ondansétron , pourra efficacement prévenir les NVPO chez des patients qui subissent une cholécystectomie laparoscopique", "In a r and omized , double-blinded study , we evaluated the analgesic effect of ketamine in the management of pain in a surgical intensive care unit after major abdominal surgery . Patients received morphine patient-controlled analgesia with either placebo ( Group M ) or ketamine ( Group K ) . Morphine was administered with initial loading doses of 2 mg until the visual analog scale ( VAS ) score was Ketamine was administered with an initial bolus of 0.5 mg/kg followed by a perfusion of 2 & mgr;g · kg−1 · min−1 during the first 24 h and 1 & mgr;g · kg−1 · min−1 during the following 24 h. The 4-h cumulative morphine doses were measured over 48 h. The VAS scores at rest and at mobilization were measured every 4 h during 48 h. A total of 101 patients were enrolled , and 93 were analyzed ( 41 in Group K and 52 in Group M ) . VAS scores at rest and at mobilization were similar . The cumulative consumption of morphine was significantly smaller in Group K ( P ketamine were a valuable adjunct to opioids in surgical intensive care unit patients after major abdominal surgery", "Abstract Background : The size of laparoscopic instruments has been reduced for use in abdominal video endoscopic surgery . However , it has yet to be proven that microlaparoscopic surgery will actually result in clinical ly relevant benefits for patients . Methods : Fifty patients were r and omized in a blinded fashion to receive either elective laparoscopic ( MINI ) , ( n= 25 ) or microlaparoscopic ( MICRO ) ( n= 25 ) cholecystectomy . Pulmonary function ( FVC , FEV 1 ) , analgesic consumption during patient-controlled analgesia ( PCA ) , pain perception by visual analogue score ( VAS ) , and the cosmetic result ( by the patient 's self- assessment ) were evaluated postoperatively as clinical ly relevant end points . Results : Age , sex , body mass index ( BMI ) , preoperative pulmonary function , pain perception , and operative time were similar for the two groups . At 8:00 PM on the day of surgery , FVC ( MINI : 1.96 L [ range , 1.48–2.48 ] ; MICRO : 2.13 L ) [ ( range , 1.61.–2.50 ) ] and FEV 1 ( MINI : 1.17 L/sec ) [ range , 0.87–1.48 ] ; MICRO : 1.34 L/sec [ range , 1.05.–2.14 ] were also similar ( each p= 0.5 ) . From surgery to the 3rd postoperative day , cumulative PCA morphine doses were comparable ( MINI : 0.15 mg/kg bw [ range , 0.09–0.23 ] ; MICRO : 0.21 mg/kg bw [ range , 0.10–0.42 ] ; p= 0.4 ) , but overall VAS scores for pain while coughing were higher in the laparoscopic group ( 406 [ range , 358–514 ] ) than in the microlaparoscopic group ( 365 [ range , 215–427 ] ; p= 0.02 ) . The cosmetic result was judged to be slightly superior by the microlaparoscopic patients ( 10 [ range , 9–10 ] ) , as compared to those in the laparoscopic ( 9 [ range , 8–10 ] ) group ( p= 0.04 ) . Conclusion : Because microlaparoscopic cholecystectomy has some minor advantages over laparoscopic surgery , it should be considered for use in selected patients", "OBJECTIVE To compare the transumbilical technique of laparoscopic cholecystectomy with st and ard laparoscopic cholecystectomy . DESIGN R and omised open study . SETTING Teaching hospital , Italy . SUBJECTS 90 patients who required elective cholecystectomy under general anaesthesia . INTERVENTIONS St and ard laparoscopic cholecystectomy through 4 ports or transumbilical cholecystectomy through 2 ports . MAIN OUTCOME MEASURES Amount of pain and analgesia , cost , side effects , and cosmesis . RESULTS 25 patients were excluded from analysis ( 8 in the st and ard group because relevant data were not recorded ; and 17 in the transumbilical group in 4 of whom relevant data were not recorded , and 13 for technical reasons ) . 32 patients who had st and ard , and 25 who had transumbilical cholecystectomy had operative cholangiograms . There were no complications , no side effects , and no conversions to open cholecystectomy . Those who had transumbilical cholecystectomy had significantly lower pain scores ( p less analgesia during the first 24 hours ( p st and ard laparoscopic cholecystectomy . CONCLUSION Once the learning curve has been completed , transumbilical cholecystectomy is possible without some of difficulties associated with st and ard laparoscopic cholecystectomy", "Background Helium is an inert gas that , if used for insufflation during laparoscopy , may be followed by less postoperative pain than carbon dioxide ( CO2 ) insufflation , due to a more limited effect on intraabdominal pH and metabolism . Saline lavage has also recently been shown to reduce postoperative pain following laparoscopic surgery . To evaluate these possibilities and to better define the clinical safety of helium insufflation , we undertook a prospect i ve r and omized trial comparing CO2 and helium insufflation with or without saline lavage in patients undergoing elective laparoscopic upper abdominal surgery . Methods From January to November 2000 , 173 patients undergoing elective laparoscopic cholecystectomy or fundoplication were r and omized to undergo laparoscopy with either CO2 or helium insufflation . Within each group , patients were further r and omized to undergo peritoneal lavage with 2 L of 0.9 % saline at the end of the surgical procedure . This yielded the following four patient groups ; CO2 ( group 1 , n=47 ) , CO2+saline lavage ( group 2 , n=43 ) , helium ( group 3 , n=43 ) and helium + saline lavage ( group 4 , n=40 ) . Patients were blinded to their r and omization , and post-operative assessment was also performed by a blinded investigator , who applied a st and ardized scoring system to assess postoperative pain . Results The study groups were well matched for age , sex , weight , American Society of Anesthesiologists ( ASA ) status , duration of surgery , and volume of gas utilized , and 81 % of patients were discharged within 48 h. There were no differences in the incidence of postoperative complications among the study groups , and postoperative pain scores were not significantly different when all four groups were compared . When helium ( groups 3 and 4 ) was compared with CO2 ( groups 1 and 2 ) , no differences in pain score were seen . When no lavage ( groups 1 and 3 ) was compared with lavage ( groups 2 and 4 ) , less pain was found in the group undergoing saline peritoneal lavage ( mean 4-h pain score , 5.9 vs 5.2 ; 24-h pain score , 4.8 vs 4.1 ; p>0.05 ) . Conclusions The use of helium insufflation for laparoscopic surgery , while not associated with any significant adverse sequelae , was not associated with less postoperative pain in this trial . The use of saline peritoneal lavage was associated with less pain in the early postoperative period", "Background and Objectives The aim of this study was to compare the efficacy and safety of two anesthesia techniques , combined epidural/general anesthesia ( CEGA ) versus total intravenous anesthesia ( TIVA ) , for laparoscopic cholecystectomy . Methods Forty patients were r and omly assigned to one of two different groups : group A received TIVA and group B received CEGA . At preset times during the operation , systolic and diastolic arterial pressure , heart rate , oxygen saturation ( SaO2 ) and end-tidal carbon dioxide ( Etco2 ) were monitored . Postoperatively , recovery ( Steward 's test ) and analgesia ( visual analog scale [ VAS ] pain scores ) were assessed , as well as the incidence of adverse effects . Results The groups were comparable as to demographic data and duration of surgery and of anesthesia . Intraoperative parameters also showed no statistical differences . Both groups had a rapid recovery ( Steward score of 6 within 12 minutes ) , but group B showed better recovery scores at 4 minutes . Postoperative pain was well controlled in both groups , but group B exhibited better scores at postoperative hour 2 . The incidence of postoperative side effects was low in both groups . Conclusions The use of CEGA for laparoscopic cholecystectomy seems to be effective and safe and to offer some advantages as compared to TIVA alone . CEGA can control pain due to CO2-induced peritoneal irritation , providing excellent intra- and postoperative analgesia . CEGA does not require the use of intraoperative intravenous opioids and shortens recovery time , without increasing the incidence of side effects", "BACKGROUND After laparoscopic cholecystectomy , the duration of convalescence is 2 to 3 weeks with an unclear pathogenesis . This study was undertaken to analyze postoperative recovery after uncomplicated elective laparoscopic cholecystectomy . METHODS Twenty-four consecutive unselected employed patients were followed up prospect ively from 1 week before to 1 week after outpatient laparoscopic cholecystectomy . Daily computerized monitoring of physical motor activity and sleep duration and night sleep fragmentation ( actigraphy ) , subjective sleep quality , pulmonary function , pain , and fatigue were registered . Treadmill exercise performance ( preoperatively and at postoperative days 2 and 8) and nocturnal pulse oximetry at the patients ' homes ( preoperatively and postoperative nights 1 - 3 ) were completed . RESULTS Median age was 41 years ( range , 21 - 56 ) . Compared with preoperatively , levels of physical motor activity , fatigue , and pain scores were normalized 2 days after operation . Subjective sleep quality was significantly worsened on the first postoperative night , and sleep duration was significantly increased on the first 2 postoperative nights . There were no significant perioperative changes in actigraphy night sleep fragmentation , incidence of self-reported awakenings or nightmares/distressing dreams , exercise performance , or nocturnal oxygenation . Pulmonary peak flow measurements were normalized the day after operation . CONCLUSION After uncomplicated outpatient laparoscopic cholecystectomy , there is no pathophysiologic basis for recommending a postoperative convalescence of more than 2 to 3 days in otherwise healthy younger patients", "A double-blind , r and omized study was conducted to examine the effect of different types of therapeutic suggestions , administered during general anaesthesia , on post-operative course . Eighty-two patients undergoing cholecystectomy were intra-operatively exposed to either affirmative and non-affirmative suggestions , affirmative or non-affirmative suggestions separately , or some irrelevant text . Patients who had received both affirmative and non-affirmative suggestions spent less time in hospital than patients in the other three groups . No significant differences were demonstrated for subjective well-being measured on the third and sixth days", "The difference in analgesic activity following lumbar ( group I ) or thoracic ( group II ) epidural administration of 50 micrograms sufentanil was studied after cholecystectomy . Fifteen patients in each group were evaluated for pain relief using a linear analog scale ( LAS ) , heart rate ( HR ) , mean arterial pressure ( MAP ) , respiratory rate ( RR ) , peak expiratory flow ( PEF ) , forced vital capacity ( FVC ) , forced expiratory volume ( FEV1 ) and arterial CO2 tension ( PaCO2 ) . In five additional patients in each group 75 micrograms sufentanil was injected for determination of serum levels . Pain scores were lower than three in both groups after 10 min , while mean pain scores remained below one from 20 min until 2 h following injection in both groups . Satisfactory pain relief lasted for 4 h. RR was significantly decreased from two until 360 min . in the lumbar group and from five until 120 min in the thoracic group . PaCO2 was raised in both groups only during the first hour . PEF and FVC were significantly improved compared to control 1 , 2 and 4 h following injection . Serum sufentanil levels reached a maximum of 0.299 + /- 0.052 ng.ml-1 in the lumbar group and 0.377 + /- 0.076 ng.ml-1 in the thoracic group after 5 min . There were no significant differences between the two groups in the variables studied", "BACKGROUND To assess the incidence of postoperative nausea and vomiting after total intravenous anesthesia ( TIVA ) with propofol versus inhalational anesthesia with isoflurane-nitrous oxide , the authors performed a r and omized trial in 2,010 unselected surgical patients in a Dutch academic institution . An economic evaluation was also performed . METHODS Elective in patients ( 1,447 ) and out patients ( 563 ) were r and omly assigned to inhalational anesthesia with isoflurane-nitrous oxide or TIVA with propofol-air . Cumulative incidence of postoperative nausea and vomiting was recorded for 72 h by blinded observers . Cost data of anesthetics , antiemetics , disposables , and equipment were collected . Cost differences caused by duration of postanesthesia care unit stay and hospitalization were analyzed . RESULTS Total intravenous anesthesia reduced the absolute risk of postoperative nausea and vomiting up to 72 h by 15 % among in patients ( from 61 % to 46 % , P cost of anesthesia was more than three times greater for propofol TIVA . Median duration of stay in the postanesthesia care unit was 135 min after isoflurane versus 115 min after TIVA for in patients ( P Duration of hospitalization was equal in both arms . CONCLUSION Propofol TIVA results in a clinical ly relevant reduction of postoperative nausea and vomiting compared with isoflurane-nitrous oxide anesthesia ( number needed to treat = 6 ) . Both anesthetic techniques were otherwise similar . Anesthesia costs were more than three times greater for propofol TIVA , without economic gains from shorter stay in the postanesthesia care", "Twenty-four patients who were to undergo cholecystectomy were r and omised into two groups , one to receive postoperative analgesia with interpleural bupivacaine , 20 ml of a 0.5 % solution with adrenaline 5 micrograms/ml , and the other to receive intramuscular pethidine , 1 mg/kg . Preoperative and postoperative pulmonary function , postoperative pain scores , and days from operation to hospital discharge were recorded and statistically compared . There was no significant difference in pain scores , nor in days to discharge ; however , postoperative pulmonary mechanics were significantly poorer in the interpleural group . A hypothesis to explain the differences is offered", "Sixty-six patients undergoing cholecystectomy were r and omly allocated to receive either intercostal blockade with bupivacaine supplemented with papaveretum or papaveretum alone for postoperative analgesia . Both groups were similar regarding distribution of sex , age , and weight . These two groups were compared . Patients who did not have intercostal blockade required postoperative analgesia sooner . There was no significant difference , however , in the total consumption of papaveretum . Both groups experienced similar degrees of pain , and there were no differences in postoperative pulmonary function . We conclude that although single intercostal blockade is an effective analgesic , it does not improve pain relief and does not improve pulmonary function after cholecystectomy when compared with a regimen of on-dem and , intramuscularly administered papaveretum", "Purpose To examine the combined preemptive effects of somatovisceral blockade during laparoscopic cholecystectomy ( LC ) . Methods One hundred fifty-seven patients under general anesthesia receiving local infiltration and /or topical peritoneal local anesthesia were studied . Patients were r and omized to receive a total of 150 mg ( 0.25 % 60 mL ) bupivacaine via periportal ( 20 mL ) and intraperitoneal ( 40 mL with 1:200,000 epinephrine ) administration of each . Group A received preoperative periportal bupivacaine before incision and intraperitoneal bupivacaine immediately after the pneumoperitoneum . Group B received periportal and intraperitoneal bupivacaine at the end of the operation . Group C ( preoperative ) and Group D ( postoperative ) received only periportal bupivacaine and Group E ( preoperative ) and Group F ( postoperative ) received only intraperitoneal bupivacaine . The control group received no treatment . Pain and nausea were recorded at one , two , three , six , nine , 12 , 24 , 36 , and 48 hr postoperatively . Results Throughout the postoperative 48 hr , incisional somatic pain dominated over other pain localizations in the control group ( P incisional pain of groups A , B , C and D was significantly lower than that of the control group in the first and second hours . The incisional pain of groups A and C was significantly lower than that of the control group in the first three hours . Conclusion Incisional pain dominated during the first two postoperative days after LC . Preoperative somato-visceral or somatic local anesthesia reduced incisional pain during the first three postoperative hours . A combination of somato-visceral local anesthetic treatment did not reduce intraabdominal pain , shoulder pain or nausea more than somatic treatment alone . Preoperative incisional infiltration of local anesthetics is recommended . RésuméObjectifVérifier les effets préventifs d’un blocage somato-viscéral combiné , réalisé pendant la cholécystectomie laparoscopique (CL).MéthodeCent cinquante-sept patients sous anesthésie générale ont reçu une infiltration locale et/ou une anesthésie locale péritonéale topique . Les patients , répartis de façon aléatoire , ont reçu au total 150 mg ( 0,25 % 60 mL ) de bupivacaïne administrée par la voie périportale ( 20 mL ) et intrapéritonéale ( 40 mL avec I : 200 000 d’épinéphrine ) . Les modalités intergroupes sont les suivantes : dans le groupe A , une dose préopératoire périportale avant l’incision et une dose intrapéritonéale immédiatement après le pneumopéritoine ; dans le groupe B , une dose périportale et une intrapéritonéale à la fin de l’opération ; dans les groupes C ( préopératoire ) et D ( postopératoire ) , seulement une périportale et dans les groupes E ( préopératoire ) et F ( postopératoire ) , seulement intrapéritonéale . Le groupe témoin n’a reçu aucun médicament . La douleur et les nausées ont été notées à une , deux , trois , six , neuf , 12 , 24 , 36 et 48 h après l’intervention . RésultatsPendant les 48 h d’observation postopératoire , la douleur somatique de l’incision a dominé toute autre douleur chez les patients témoins ( P douleur incisionnelle a été significativement plus faible dans les groupes A , B , C et D que dans le groupe témoin pendant les deux premières heures . Elle a aussi été significativement plus faible dans les groupes AetC que dans le groupe témoin pendant les trois premières heures . Conclusion La douleur incisionnelle a dominé pendant les deux premiers jours qui ont suivi la CL . L’anesthésie préopératoire somatoviscérale ou somatique locale ont réduit la douleur incisionnelle pendant les trois premières heures postopératoires . Une combinaison d’anesthésiques locaux somatoviscéraux n’a pas réduit la douleur intra-abdominale , la douleur à l’épaule ou les nausées davantage que l’anesthésie somatique employée seule . L’Infiltration préopératoire d’anesthéslque local au site d’Incision est recomm and ée", " We studied 24 patients undergoing elective cholecystectomy and r and omized to either conventional postoperative pain treatment , with intermittent nicomorphine ( 10 to 15 mg ) and acetaminophen ( 1 gm ) on request , or thoracic epidural analgesia with plain bupivacaine for 48 hours and epidural morphine 4 mg every 8 hours for 96 hours plus systemic indomethacin 100 mg every 8 hours for 96 hours . Epidural analgesia for pin prick extended from the fourth thoracic to the first lumbar nerve for 48 hours . Assessment s of pain , various injury response parameters , peak flow , and subjective feeling of fatigue were performed preoperatively , 3 and 6 hours after skin incision , and 1 , 2 , 4 , and 8 days postoperatively . The epidural analgesia-systemic indomethacin treatment eliminated postoperative pain during rest and coughing . In contrast , only a minor and clinical ly unimportant modulation of the conventional perioperative and postoperative changes in plasma cortisol , glucose , transferrin , orosomucoid , leukocyte and differential counts , rectal temperature , peak flow , and fatigue was observed . Our results suggest that factors other than pain per se must be controlled in order to reduce postoperative morbidity", "The effect of intraperitoneal bupivacaine on postoperative pain was studied in 60 ASA 1–2 patients undergoing elective laparoscopic cholecystectomy . The patients were r and omly selected ( 20 patients in each group ) to receive in double‐blind fashion 100 ml of either plain 0.15 % bupivacaine { 150 mg · 100 ml‐1 ) or the same solution with adrenaline ( 1.5 μg ml‐l ) , or the same volume of saline into the right subdiaphragmatic space at the end of surgery . The patients were kept in the Trendelenburg 's position for 20 min after the instillation . Venous blood sample s for the determination of bupivacaine plasma concentrations were drawn up to 180 min . Plasma bupivacaine concentrations peaked at 30 min ( highest individual value 2.6 μg ml‐1 ) after instillation . Bupivacaine concentrations were significantly lower in the bupivacaine‐adrenaline group . During the follow‐up no difference between the groups occurred as to the time to first dem and of analgesia , severity of postoperative pain , amount of consumed analgesics during 7 days , and length of hospitalization . In all groups , 30–45 % of the patients complained of right shoulder pain . After the first 24 hours , pain at rest and during moving was reported as mild and was managed with oral ketoprofen", "The incidence and pattern of postoperative muscle pains was studied in 155 healthy women undergoing outpatient laparoscopic surgery who were assigned r and omly to one of five treatment groups . Group 1 ( control ) received thiopental and succinylcholine , 1 mg/kg , followed by enflurane and nitrous oxide . Group 2 received d-tubocurarine , 3 mg , followed by succinylcholine , 1.5 mg/kg , but was otherwise similar to Group 1 . Groups 3 and 4 were similar to Group 1 , but received propofol instead of thiopental , and Group 4 also received a variable-rate propofol infusion instead of enflurane . Finally , Group 5 was similar to Group 3 , but received atracurium instead of succinylcholine . Muscle fasciculations were often observed in Groups 1 , 3 , and 4 , but were attenuated in Group 2 and absent in Group 5 . Overall , postoperative shoulder pain occurred in 81 % , 72 % , and 29 % of patients on the first , second , and third postoperative days , respectively . The incidence of this symptom did not differ among the five groups . Neck pain occurred less frequently than shoulder pain in each group , and also occurred less often in Group 5 than in Group 1 . Muscle stiffness occurred less often than muscle pain , and also occurred less frequently in Group 5 than in Group 1 . In conclusion , succinylcholine contributes to neck pain and muscle stiffness after laparoscopic procedures . Compared to thiopental and enflurane , the use of propofol for induction and /or maintenance of anesthesia failed to alter the incidence of postlaparoscopic muscle pain or stiffness", "Background The effects of intraperitoneal administration of bupivacaine on pain after laparoscopic cholecystectomy were studied in a prospect i ve , double‐blind , r and omised trial . Methods : Eighty ASA 1 and 2 patients were r and omly assigned to one of two groups . Immediately after pneumoperi‐toneum was obtained patients in group 1 were given 15 ml of 0.5 % bupivacaine injected under direct vision into the hepato‐diaphragmatic space , near and above the hepato‐duodenal ligament and above the gallbladder . At the end of operation another 15 ml of bupivacaine was injected . Patients in group 2 were given 15 ml of 0.9 % saline solution in a similar fashion . Postoperative pain was assessed using a visual analogue scale ( VAS 100 mm ) at 0.5,4 , 8,12 and 24 h after surgery . Analgesic consumption was also recorded", "Background : Laparoscopic cholecystectomy is characterized by a short hospital stay . Hence , pain control on the day of surgery is increasingly important . The aim of this study was to evaluate the effect of intraperitoneal bupivacaine on pain relief following laparoscopic cholecystectomy . Methods : Sixty patients undergoing elective laparoscopic cholecystectomy were prospect ively r and omized into 2 groups . Following removal of the gallbladder , group A received 100 mg of bupivacaine in 50 cc of saline , installed into the gallbladder bed and right subphrenic space . Group B received saline without bupivacaine . Pain was assessed using a visual/analog scale at fixed-time intervals . Results : No significant difference occurred in the average pain levels between the groups at 1 , 2 , 4 , and 14 hours postsurgery . The average analgesic requirement was lower in the bupivacaine group , but this did not reach statistical significance . Conclusion : Application of intraperitoneal bupivacaine did not attenuate pain following laparoscopic cholecystectomy , and no role exists for its routine use", "Purpose To compare the efficacy of tramadol and morphine for intra- and postoperative analgesia in patients undergoing laparoscopic cholecystectomy . Methods In a prospect i ve , r and omized , double-blind study 100 patients were allocated r and omly into two groups . Ten minutes before induction of anaesthesia , patients in group I received 100 mg tramadol and those in group 2 received 10 mg morphineiv . Anaesthesia was induced with 5 mg·kg−1 thiopental and was maintained with O2 , N2O plus isoflurane with additional doses of tramadol or morphine as decided by the attending anaesthetist . Postoperatively , patients in group I and group 2 received tramadol and morphine , respectively , from a patient-controlled analgesia ( PCA ) device . Pain , analgesic consumption , vital signs and side effects were recorded postoperatively for 24 hr . Results Intraoperative consumption of tramadol and morphine were 137 ± 37 and 12.2 ± 3 mg , respectively . Compared with morphine , patients receiving tramadol had higher blood pressures and required greater mean ETiso to control haemodynamic variables ( P in observer pain score or visual analogue pain score during the first 24 hr between groups except at 30 , 45 , and 90 min where patients in the tramadol group reported higher pain scores ( P 24 hr PCA consumption was III ± 93 and 7.5 ± 6.6 mg of tramadol and morphine , respectively . Conclusions There was no difference between the use of tramadol and morphine to treat pain after laparoscopic cholecystectomy from 90 min after the end of surgery . Morphine was more effective than tramadol as an intraoperative analgesic . RésuméObjectifComparer l’efficacité du tramadol et de la morphine pour l’analgésie peropératoire et postopératoire de patients devant subir une cholécystectomie laparoscopique . MéthodeLors d’une étude prospect i ve , r and omisée et en double aveugle , 100 patients ont été répartis au hasard en deux groupes . Dix minutes avant l’induction de l’anesthésie , les patients du groupe I ont reçu 100 mg de tramadol et ceux du groupe 2 , 10 mg de morphineiv . Lanesthésie a été induite avec 5 mg·kg−1 de thiopental et a été maintenue avec un mélange d’O2 et de N2O plus de l’isoflurane et des doses supplémentaires de tramadol ou de morphine selon la décision de l’anesthésiste traitant . Après l’intervention , les patients des groupes 1 et 2 ont reçu respectivement du tramadol et de la morphine à l’aide d’un dispositif d’analgésie contrôlée par le patient ( ACP ) . En période postopératoire également , on a enregistré pendant 24 heures la douleur , la consommation d’analgésiques , les signes vitaux et les effets secondaires . RésultatsLa consommation peropératoire de tramadol et de morphine a été de 137 ± 37 et de 12,2 ± 3 mg , respectivement . Comparativement , les patients qui ont reçu du tramadol ont présenté une tension artérielle plus élevée et ont eu besoin d’isofluraneTE ( télé-expiratoire ) de moyenne plus élevée pour contrôler les variables hémo-dynamiquesP intenses ( P La consommation totale des 24 h d’ACP a été de 111 ±93 et de 7,5 ± 6,6 mg de tramadol et de morphine , respectivement . Conclusion À partir de 90 min après la chirurgie , il n’y a pas de différence entre l’usage de tramadol ou de morphine pour traiter la douleur consécutive à la cholécystectomie laparoscopique . La morphine a été plus efficace que le tramadol en tant qu’analgésique peropératoire", "The authors compared the analgesic efficacy of one dose of oral ibuprofen with that of intravenously administered fentanyl for relief of pain after outpatient laparoscopic surgery . Thirty healthy female patients received either 800 mg of oral ibuprofen preoperatively or 75 micrograms of intravenous fentanyl intraoperatively plus respective intravenous or oral placebos in a r and omized , double-blind manner . Patients recorded their degree of pain and nausea in the recovery room , in the same-day surgery stepdown unit , during the ride home , and upon arrival at home . The postanesthesia care nurse recorded the amount of fentanyl and droperidol needed to treat pain and nausea in the recovery room . Patients who received ibuprofen were more comfortable in the stepdown unit ( P less than 0.05 ) and after arrival home ( P less than 0.05 ) than those in the fentanyl group . Additionally , patients who received ibuprofen had lower nausea scores in the step-down unit ( P less than 0.05 ) ; this may have been related to the lower total fentanyl dose in these patients . The authors conclude that ibuprofen may be a useful alternative to fentanyl for providing postoperative analgesia for outpatient surgery", "Shoulder pain ( SP ) is frequently mentioned in recent literature following laparoscopic operations . In the literature , many causes have been declared to explain shoulder pain after CO2 insufflation , such as direct peritoneal irritation of the CO2 gas , excessive traction of the triangular ligament , and overstretching of the diaphragmatic muscle fibers due to the high rate of insufflation . This study was planned as multicentric , and 76 patients , aged between 35 to 45 , were entered into the study . They were all selected by a r and omized sampling method , with equal numbers of men and women , to achieve true evaluation . The low flow-rate ( LFR ) group was insufflated with 2.5 L/min and the high flow-rate ( HFR ) group with 7.5 L/min . All cases were evaluated by subjective pain classification on postoperative day 3 . According to the subjective pain scale method , shoulder pain average was 23.9+/-3.1 in the LFR group and 55.4+/-6.5 in the HFR group . The difference between these groups was significant ( p > 0.01 ) . There is no significant difference for the operation time ( LFR% : 64+/-15 minutes , HFR : 61+/-20 minutes , p > 0.05 ) . Our results suggest that there is a significant statistical relation between the postoperative shoulder pain levels and increased insufflation rates . For this reason , low insufflation rate significantly reduces the shoulder pain but does not increase the operation time . Therefore , a low insufflation rate should be applied in all cases for patients ' comfort and safety", "Background and objective : The reported incidence of shoulder tip pain following laparoscopic surgery varies from 35 to 63 % . This study evaluated the analgesic efficacy of either performing a prophylactic suprascapular nerve block with bupivacaine or applying a piroxicam patch to the skin over both shoulders for the relief of shoulder tip pain after laparoscopy . Methods : Sixty healthy informed female patients were r and omly assigned to one of three groups : ( a ) a control group ( n = 20 ) , no treatment ; ( b ) a suprascapular nerve block group ( n = 20 ) in which a bilateral suprascapular nerve block was performed before induction of anaesthesia with 5 mL 0.5 % bupivacaine with epinephrine ; and ( c ) a piroxicam patch group ( n = 20 ) in which a 48 mg piroxicam patch on the skin of each shoulder was applied before induction of anaesthesia . All patients received a total intravenous anaesthesia technique with propofol , fentanyl and vecuronium . Shoulder tip and wound pain were recorded on a visual analogue pain scale at five time intervals for 24 h after surgery . Results : A total of 80 % of patients in the control group , 75 % in the suprascapular nerve block group and 45 % in the piroxicam patch group complained of shoulder tip pain during the recording period ( P scores for shoulder tip pain in the piroxicam patch group were significantly lower compared with the control group at 3 , 6 and 12 h , and compared with the suprascapular nerve block group at 6 and 12 h. The need for analgesics was also significantly lower in the piroxicam patch group compared with the other two groups . Conclusions : Prophylactic piroxicam patches are effective and safe for the relief of shoulder tip pain after laparoscopy . Bilateral suprascapular nerve block is not effective in this setting", "Ketorolac , a nonsteroidal anti-inflammatory drug , is alleged to produce postoperative analgesia without opioid-related side effects . Patients undergoing laparoscopic cholecystectomy were assigned r and omly to receive either ketorolac or a placebo ( saline ) according to a double-blind protocol . Preoperative ( baseline ) pulmonary function was evaluated using a Respiradyne II monitor . Patients received midazolam , 2 mg , and 2 mL of either ketorolac , 60 mg ( n = 311 , or saline ( n = 29 ) , 20–40 min before surgery . Anesthesia consisted of thiopental , 4–5 mg/kg , and vecuronium , 0.1 mg/kg , for induction , and isoflurane , 0.5%–2.0 % , with 67 % nitrous oxide in oxygen for maintenance . A second 2-mL dose of the same study medication ( ketorolac , 60 mg , or saline ) was administered 4 h after the initial dose . Post-operatively , 66 % of patients in the saline group complained of pain requiring treatment with fentanyl compared to 32 % in the ketorolac group ( P respect to postoperative sedation , anxiety , pain , or nausea visual analog scores . Compared to the preoperative values , significant decreases in pulmonary function tests were noted in both groups at 4 h after the operation and the following morning ( P values of forced expiratory volume at 1 s and forced expiratory flow at 25%–75 % of the forced vital capacity at 4 h after the operation were significantly higher than those in the saline group ( P of nausea ( 45 % vs 52 % ) and vomiting ( 10 % vs 10 % ) were similar in both groups . In conclusion , ketorolac decreased the postoperative requirement for opioid analgesic medication . However , the use of ketorolac failed to decrease postoperative emesis or ventilatory impairment after laparoscopic cholecystectomy", "BACKGROUND Laparoscopic cholecystectomy ( LC ) is traditionally performed with two 10-mm and two 5-mm trocars . The effect of smaller port incisions on pain has not been established in controlled studies . METHODS In a double-blind controlled study , patients were r and omized to LC or cholecystectomy with three 2-mm trocars and one 10-mm trocar ( micro-LC ) . All patients received a multimodal analgesic regimen , including incisional local anesthetics at the beginning of surgery , NSAID , and paracetamol . Pain was registered preoperatively , for the first 3 h postoperatively , and daily for the 1st week . RESULTS The study was discontinued after inclusion of 26 patients because five of the 13 patients ( 38 % ) r and omized to micro-LC were converted to LC . In the remaining 21 patients , overall pain and incisional pain intensity during the first 3 h postoperatively increased in the LC group ( n = 13 ) compared with preoperative pain levels ( p pain did not increase in the micro-LC group ( n = 8) . CONCLUSIONS Micro-LC in combination with a prophylactic multimodal analgesic regimen reduced postoperative pain for the first 3 h postoperatively . However , the micro-LC led to an unacceptable rate of conversion to LC ( 38 % ) . The micro-LC instruments therefore need further technical development before this surgical technique can be used on a routine basis for laparoscopic cholecystectomy", "Background Opioids can produce peripheral analgesic effects by activation of opioid receptors on sensory nerves . This study was design ed ( 1 ) to examine a novel route of opioid administration , the intraperitoneal injection ; ( 2 ) to compare this to interpleural application , and ( 3 ) to compare opioid with local anesthetic effects under both conditions . Methods At the end of laparoscopic cholecystectomy , 110 patients received the following injections in a double‐blind , r and omized manner : Group 1 ( n = 18 ) was given intraperitoneal morphine ( 1 mg in 20 ml saline ) and 20 ml intravenous saline . Group 2 ( n = 17 ) received intraperitoneal saline and 1 mg intravenous morphine . Group 3 ( n = 15 ) received 20 ml 0.25 % intraperitoneal bupivacaine and intravenous saline . Group 4 ( n = 20 ) received interpleural morphine ( 1.5 mg in 30 ml saline ) and 30 ml intravenous saline . Group 5 ( n = 20 ) received interpleural saline and 1.5 mg intravenous morphine . Group 6 ( n = 20 ) received 30 ml 0.25 % interpleural bupivacaine and intravenous saline . Postoperative pain was assessed using a visual analog scale , a numeric rating scale , and the McGill pain question naire . Pain localization , supplemental analgesic consumption , vital signs , and side effects were recorded for 24 h. Results Neither intraperitoneal nor interpleural morphine produced significant analgesia after laparoscopic cholecystectomy ( P > 0.05 , Kruskal‐Wallis test ) , whereas interpleural bupivacaine was effective ( P 0.05 , Kruskal‐Wallis test ) . Shoulder pain was not prevalent in the majority of patients during the first 6 h. By 24 h , about half of the patients complained of shoulder pain , which was rated “ low ” by about one‐third of all patients . No significant side effects occurred . Conclusions Interpleural bupivacaine ( 0.25 % ) produces analgesia after laparoscopic cholecystectomy . We attribute the lack of effect of intraperitoneal injections to the small dose and to a rapid dilution within the peritoneal cavity . The fact that interpleural morphine ( 0.005 % ) is ineffective may be due to an intact perineurial barrier in the noninflamed pleural cavity , which restricts the transperineurial passage of morphine to opioid receptors on intercostal nerves", "The effects of intraperitoneal administration of bupivacaine on pain and the sympathoadrenal response to surgery were studied in a double‐blind r and omized trial in 19 patients undergoing cholecystectomy . Bupivacaine ( 2 mg/kg ) was dissolved in 300 ml isotonic saline and administered into the peritoneal cavity 10 min before the operation ( n = 9 ) . Saline was administered in a comparable group of patients ( n = 10 ) . There were no significant differences in pain scores between the groups during the first day after surgery ( P>0.05 ) . Postoperative requirements of pethidine during the first 2 days after surgery did not differ significantly between the groups . Blood glucose levels were significantly lower in the bupivacaine‐treated group 1 h ( P regarding plasma catecholamine and serum cortisol levels during and after surgery . Differences between the groups regarding urine output of catecholamines during the first and second postoperative days were not significant . Our results suggest that single administration of a local anesthetic intraperitoneally does not reduce pain or the sympathoadrenal response to upper abdominal surgery", "We have evaluated the antiemetic effect of i.v . dexamethasone compared with saline in the prevention of nausea and vomiting after laparoscopic cholecystectomy . We studied 90 patients requiring general anaesthesia for laparoscopic cholecystectomy , in a r and omized , double-blind , placebo-controlled study . The dexamethasone group ( n = 45 ) received dexamethasone 8 mg i.v . and the saline group received saline 2 ml i.v . at induction of anaesthesia . Anaesthesia was maintained with isoflurane in oxygen . We found that 10 % of patients in the dexamethasone group compared with 34 % in the saline group reported vomiting ( P total incidence of nausea and vomiting was 23 % in the dexamethasone group and 63 % in the saline group ( P dexamethasone 8 mg significantly decreased the incidence of nausea and vomiting after laparoscopic cholecystectomy", "Post-laparoscopy pain can increase recovery time and delay patient discharge . While previous studies have focused on the problems of nausea and vomiting , the purpose of this study was to assess the effect of diclofenac ( a non-steroidal antiinflammatory drug ) in the treatment of post-laparoscopy pain . Diclofenac ( 50 mg ) or placebo was administered pr r and omly and double-blind , prior to induction of anaesthesia , to 46 women . Pain intensity was assessed by the patient using a visual analogue scale 1 , 12 and 24 hr after surgery . Postoperative analgesic requirements and side effects were also studied . Diclofenac result ed in better pain relief at 24 hr ( 1.0 vs 2.5 , P number of patients who needed additional postoperative analgesics ( 7 vs 15 , P incidence of side effects . These data suggest that diclofenac reduces post-laparoscopy pain and postoperative analgesic requirements . RésuméLa douleur postlaparoscopique ralentit la récupération et retarde le congé . Alors que des études antérieures portaient sur les phénomènes de nausées et de vomissements , l’objectif de cette étude est d’évaluer les effets du diclofénac ( un antiinflammatoire non-stéroïdien ) sur la douleur postlaparascopie . Le diclofénac 50 mg ou un placébo sont administrés à 46 femmes au hasard et à double insu par la voie rectale avant l’induction de l’anesthésie . L’intensité de la douleur est évaluée par la patiente à l’aide d’une échelle visuelle analogique 1 hre , 12 et 24 hres après la chirurgie . Les besoins analgésiques postopératoires et les effets secondaires sont aussi étudiés . Le diclofénac produit un meilleur soulagement à 24 hres ( 1,0 vs 2,5 , P d’analgésiques additionnels ( 7 vs 15 , P des effets secondaires . Ces données suggèrent que le diclofénac diminue la douleur postlaparoscopie et les besoins postopératoires d’analgésiques", "INTRODUCTION The positive CO2 pneumoperitoneum needed to create the working space for laparoscopic surgery may induce pathophysiological changes . Concern about these changes has led to the introduction of a gasless technique . The aim of the present study was to compare the gasless CLC and GLC with regard to exposure , technical problems , operation time , postoperative pain , clinical course , and convalescence . MATERIAL AND METHODS Fifty consecutive patients with symptomatic gallstones were r and omised to conventional ( CLC ) or gasless laparoscopic cholecystectomy ( GLC ) , with special reference to overall patient satisfaction , technical difficulties , duration of surgery , postoperative pain , and recovery . RESULTS The overall exposure of the operative field was poorer in the GLC group , whereas the duration of surgery , steps involved in the cholecystectomy technique , length of hospital stay , and postoperative pain score did not differ significantly . The period to return to normal activity was significantly shorter in the GLC group , six days compared to 8.5 days in the CLC group ( p fatigue , dizziness and nausea , and overall satisfaction with the outcome . DISCUSSION This study shows that convalescence is significantly shorter after laparoscopic cholecystectomy by the gasless technique than by the conventional CO2 technique . However , exposure of the operative field was less than optimal with the gasless technique", "D-myo-inositol-1,2,6-trisphosphate ( 1,2,6-IP3 ) possesses antiinflammatory properties , such as reduced eicosanoid synthesis and inhibition of inflammationinduced edema . These properties suggest possible analgesic effects . The analgesic effect of 1,2,6-IP3 was evaluated in a double-blind , r and omized study in 24 patients undergoing cholecystectomy . Ten patients received 1,2,6-IP3 as an intravenous ( IV ) bolus dose of 240 mg , followed by a continuous IV infusion at 90 mg/h for 24 h. The placebo group ( n = 14 ) received corresponding volumes of isotonic saline . Postoperative pain ( visual analog pain scale ; VAS ) and opiate analgesic requirements ( ketobemidon ) were evaluated during five postoperative days . Results showed significantly reduced pain during the first five postoperative days in patients treated with 1,2,6-IP ( 3 ) , as measured by using a VAS ( P requirements of opioid analgesics were significantly reduced during the first three postoperative days ( P drug-related side effects were observed . Results of the present study demonstrate a potent and long-lasting analgesic effect of 1,2,6-IP3 , possibly related to its antiinflammatory properties . Implication s : A new antiinflammatory drug under investigation , inositol-1,2,6-trisphosphate , was evaluated as a possible analgesic in a pilot study during the postoperative period in cholecystectomized patients . Results showed significantly lower pain assessment and opioid consumption , which should encourage further studies", "Objective : To compare blood volumes and hematologic indices between nine aerobically trained , physically active pregnant women who continued to exercise throughout gestation and five healthy yet sedentary gravidas . Methods : Subjects were tested on three occasions : 25 and 36 weeks of pregnancy and 12 weeks postpartum . Plasma volumes were estimated by dye dilution with Evans blue . Blood sample s were taken from the antecubital vein with the subjects resting in a seated , semirecumbent position . In addition to plasma volume estimations , blood sample s were analyzed for hematocrit ratio , hemoglobin concentration , red cell count , and plasma protein concentration . Blood volumes and red cell volumes were calculated from plasma volume estimates and hematocrit ratios . Results : Average birth weight and length of gestation did not differ between the subject groups . Analysis of variance indicated that absolute blood volume measures were significantly greater ( P plasma and red cell volumes ( P Blood volumes relative to body weight were significantly higher in physically active subjects ( P All vascular volumes were significantly ( P Hematologic indices of hematocrit ratio , hemoglobin concentration , red cell count , and plasma protein concentration were all greater ( P < 001 ) at 12 weeks postpartum than during pregnancy", "Background Postoperative nausea and vomiting after laparoscopic cholecystectomy remains a common problem despite routine antiemetic prophylaxis . Therefore , the authors investigated the effect of administering 4 mg intravenous dexamethasone as an adjunct to a 5-HT3 antagonist ( 12.5 mg intravenous dolasetron ) with respect to patient outcome . Methods Out patients ( N = 140 ) were enrolled in this prospect i ve , r and omized , placebo-controlled , double-blind , institutional review board – approved protocol involving two antiemetic treatment groups . After induction of anesthesia , the control group received 1 ml intravenous saline , whereas the dexamethasone group received 4 mg intravenous dexamethasone . Both groups received 12.5 mg intravenous dolasetron at the time of gallbladder removal . A blinded observer recorded the recovery times , emetic episodes , rescue antiemetics , maximum nausea score , and time to achieve discharge criteria . Postdischarge side effects , as well as patient satisfaction and quality of recovery scores were assessed at 24 h after surgery . Results Although there was no difference in the incidence of postoperative nausea and vomiting in the early recovery period , the dexamethasone group had a shorter stay in the day-surgery unit ( 136 ± 57 vs. 179 ± 62 min ) and more rapidly achieved discharge criteria ( 161 ± 32 vs. 209 ± 39 min ) . In addition , fewer patients in the dexamethasone group experienced nausea at home within 24 h after discharge ( 13 vs. 28 % , P higher quality of recovery and patient satisfaction scores ( P dexamethasone shortened the time to achieve discharge criteria and improved the quality of recovery and patient satisfaction scores after laparoscopic cholecystectomy procedures in out patients receiving prophylaxis with 12.5 mg intravenous dolasetron ", "Although postoperative pain following laparoscopic cholecystectomy ( LC ) is less intense than that after open surgery , postoperative morbidity nonetheless increases with LC . The aim of this study was to investigate whether local anesthetic infiltration of trocar sites during LC decreased postoperative pain and , if so , to find the optimum timing for local anesthesia ( LA ) . Seventy patients undergoing LC were r and omized into three groups . In the first ( control group , n = 25 ) 3 ml of 0.9 % NaCl was subcutaneously infiltrated around each 5-mm trocar site , 4 ml around each 10-mm site . In the second group ( n = 20 ) , the same volume of local anesthetic was administered in the same manner prior to surgery , and in the third group ( n = 25 ) an identical dose of local anesthetic was infiltrated at the end of surgery . A visual analog scale was given to all patients , who were asked to record their pain intensity at 1 , 3 , 5 , 7 , and 12 h postoperatively . Pethidine HCl 1 mg/kg i.m . was given to those whose pain intensities were greater than 5 . The mean pain intensities were 7.6 , 5.9 , and 5.1 in the control , preoperative , and postoperative LA groups , respectively . In the preoperative LA group , 50 % of patients and in the postoperative LA group 28 % of patients required analgesics compared with 76 % in the control group . The main pain intensities and analgesic requirements were significantly lower in the postoperative LA group compared with other groups . We conclude that local anesthesia during LC reduces postoperative pain and that infiltration of trocar sites following surgery offers better pain relief than local anesthetic given just before the incision", "Dexamethasone is an effective antiemetic drug , but the efficacy of small-dose dexamethasone 5 mg on the prophylaxis of postoperative nausea and vomiting ( PONV ) in patients undergoing laparoscopic chole-cystectomy has not been evaluated . We , therefore , evaluated the prophylactic effect of small-dose dexamethasone ( 5 mg ) on PONV in patients undergoing laparoscopic cholecystectomy . Tropisetron and saline served as controls . One-hundred-twenty patients scheduled for laparoscopic cholecystectomy were enrolled in a r and omized , double-blinded , placebo-controlled study . At the induction of anesthesia , the Dexamethasone group received IV dexamethasone 5 mg , the Tropisetron group received IV tropisetron 2 mg , and the Pla- cebo group received IV saline . We found that both dexamethasone and tropisetron significantly decreased the following variables : the total incidence of PONV ( P more than four vomiting episodes ( P proportions of patients requiring rescue antiemetics ( P Dexamethasone and Tropisetron groups were not significant . We conclude that prophylactic IV dexamethasone 5 mg significantly reduces the incidence of PONV in patients undergoing laparoscopic cholecystectomy . At this dose , dexamethasone is as effective as tropisetron 2 mg and is more effective than placebo", "Gynaecological surgery is of high emetogenic potential and both total intravenous anaesthesia ( TIVA ) and prophylactic antiemetic therapy may reduce the incidence of postoperative nausea and vomiting ( PONV ) . We studied 144 patients scheduled for day-case gynaecological laparoscopy in a r and omized trial comparing balanced inhalational anaesthesia and prophylactic dolasetron ( group I+D ) with propofol TIVA and dolasetron ( group T+D ) or TIVA alone ( group T ) . The primary outcome of “ complete response ” ( no vomiting , no treatment for PONV ) was not significantly different among groups ( 34 % , 51 % , 32 % ; groups I+D vs T+D vs T , P=0.12 ) . During the first hour after surgery , group I+D had nausea of greater severity ( P vomiting ( P nausea and 38 % vomited . The incidence and severity of nausea were significantly lower in the TIVA groups ( P complete response rate was highest and the post-discharge incidence and severity of nausea lowest in group T+D. In conclusion , propofol TIVA , with or without dolasetron , reduced postoperative nausea , but not perioperative vomiting or antiemetic requirement , when compared with inhalational anaesthesia plus dolasetron", "The antiemetic efficacy of ondansetron given prophylactically was investigated in a r and omised , double‐blind , placebo‐controlled trial of 63 patients undergoing laparoscopic cholecystectomy . The patients received intravenously prior to anaesthesia either ondansetron 4 mg or placebo . The same st and ardised general anaesthetic technique was used . Nausea , emetic episodes and the need for rescue medication were recorded for 24 h postoperatively . Nausea was experienced by 64 % of the patients in the ondansetron group and 56 % in the placebo group , and emetic episodes occurred in 45 % and 50 % of the patients in the two groups , respectively . The proportions of patients given rescue antiemetic medication were 45 % and 44 % , respectively . No clinical ly important adverse events were observed . In conclusion , ondansetron given prior to anaesthesia in a dosage of 4 mg did not prevent postoperative nausea and vomiting after laparoscopic cholecystectomy", "Postoperative pain after laparoscopic surgery is less than after laparotomy , and patients may benefit from an intraperitoneal injection of local anesthetic . Thirty-seven ASA physical status I or II patients received in double-blinded fashion 20 mL of 0.9 % saline solution ( placebo ) , ropivacaine 0.25 % ( Rop 0.25 % ) , or ropivacaine 0.75 % ( Rop 0.75 % ) immediately after trocar placement and at the end of surgery . We measured pain and morphine consumption until 20 h after surgery . Plasma ropivacaine concentrations were measured . The three groups were comparable for shoulder pain , parietal pain , and incidence of side effects . Visceral pain at rest , during cough , and on movement and total consumption of morphine were significantly smaller in Groups Rop 0.25 % and Rop 0.75 % when compared with Placebo . Although no adverse effect occurred in any patient , the largest dose led to large plasma concentrations of ropivacaine ( 2.93 ± 2.46 & mgr;g/mL and 3.76 ± 3.01 & mgr;g/mL after the first and second injection , respectively ) . We conclude that intraperitoneal administration of ropivacaine before and after surgery significantly decreases postoperative pain . Because the smaller dosage ( 2 × 50 mg ) provided similar analgesia and was associated with significantly smaller plasma concentrations than the larger dosage ( 2 × 150 mg ) , this smaller dosage seems more appropriate", "Continuous interpleural analgesia provided by 4 hourly injections of 20 ml bupivacaine 0.5 % with adrenaline 5 μg/ml was compared with placebo in a r and omised , double‐blind study after cholecystectomy . All patients self‐administered intravenous morphine using a patient‐controlled analgesia device . There was a highly significant difference in mean morphine consumption between the groups ( 72 mg as compared with 22 mg ) . Visual analogue pain scores tended to be lower in the bupivacaine group throughout and this was significant at 2 hours . Respiratory function measurements were not significantly different between the groups . The mean peak venous plasma bupivacaine concentration after the sixth dose was 3.03 μg/ml and no symptoms suggestive of local anaesthetic toxicity occurred . It is concluded that this regimen can provide effective and continuous analgesia after cholecystectomy and that combined administration of interpleural bupivacaine and systemic morphine is more effective than morphine alone in the immediate postoperative period . The doses of bupivacaine required for optimal use of the technique lead to significant total plasma bupivacaine concentrations within 24 hours", "OBJECTIVE To evaluate the efficacy of nonsteroidal anti-inflammatory drugs ( NSAIDs ) on pain after laparoscopic cholecystectomy . DESIGN A prospect i ve , r and omized , placebo-controlled , double-blind study . SETTING A university hospital . PATIENTS Fifty-two patients with cholelithiasis but without known allergy to one of the study drugs , history of bleeding , peptic ulcer disease , known cardiac , lung or renal disease , abnormal liver function or use of opiates or NSAIDs within 2 weeks before operation . Patients were assigned to one of three groups and treatment was r and omized by placing the drugs in sealed , numbered envelopes . INTERVENTION Administration of the NSAIDs ketorolac , intramuscularly , or indomethacin , rectally , before laparoscopic cholecystectomy . MAIN OUTCOME MEASURES Postoperative pain scored on a a visual analogue scale and by nurse assessment , total dose of fentanyl citrate given , and nausea or emesis . RESULTS Patients in the placebo group reported significantly more pain than either NSAID group ( p pain by the nurses ( P nausea and emesis ( p ketorolac and indomethacin , administered preoperatively , decrease early postoperative pain and nausea after laparoscopic cholecystectomy and are equally efficacious in producing these results", "OBJECTIVE To compare Nalbuphine and fentanyl as total intravenous anaesthesia with propofol infusion in laproscopic cholecystectomy cases . STUDY DESIGN Double blind r and omised . METHODS Changes in haemodynamic variables greater than twenty percent above or below the baseline and recovery profile were observed . RESULTS Blood pressure remained within 20 % of baseline in either group . Nine patients in fentanyl and fifteen in nalbuphine group required an additional bolus of propofol intraoperatively . Heart rate response after tracheal intubation was significantly higher in the nalbuphine group ( 25 % ) . No difference was observed in the incidence of nausea and vomiting in the recovery room . Twenty-seven percent patients in the nalbuphine group required analgesia in the recovery in comparison to 87 % in the fentanyl group . Patients in the fentanyl group required analgesia earlier ( 37 minutes vs. 62 minutes ) . CONCLUSION Fentanyl provided better intraoperative haemodynamic stability in comparison to nalbuphine when used as the analgesic component in total intravenous anaesthesia with propofol . The recovery profile with both drugs was similar . Lesser number of patients required analgesia in the recovery in the nalbuphine group", "Laparoscopic cholecystectomy is now widely practised . There are various methods of pain relief used but none has been assessed or compared following this procedure . We have assessed the analgesic effect of intraperitoneal bupivacaine in laparoscopic cholecystectomy . Sixty consecutive patients were r and omly assigned to one of two groups . Patients in group 1 were given 20 ml of saline injected under vision into the region of the gallbladder bed . Patients in group 2 were given 20 ml of 0.25 % bupivacaine in a similar fashion . Postoperative pain was assessed with a visual analogue pain scale and the site of pain was recorded . Patients in the bupivacaine group had less pain in the early postoperative period and a lower incidence of pain in the right hypochondrium . Intraperitoneal bupivacaine is a simple and effective treatment for postoperative pain after laparoscopic cholecystectomy", "STUDY OBJECTIVE To investigate the effect of an additional postoperative intravenous ( IV ) clonidine infusion on meperidine requirements in the early postoperative period . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Postoperative recovery room at a university medical center . PATIENTS Sixty female patients who had undergone a cholecystectomy . INTERVENTIONS On first complaining of postoperative pain , 30 patients ( clonidine group ) received clonidine 150 micrograms IV over 30 minutes and an additional 150 micrograms of clonidine during the following 90 minutes . The other 30 patients ( control group ) were given identical volumes of 0.9 % sodium chloride IV at identical time intervals . All patients received a patient-controlled analgesia device ( initial dose , meperidine 16 mg ; subsequent doses , meperidine 8 mg on dem and ; lockout time , 5 minutes ; background infusion , meperidine 2.5 mg/hr ) . MEASUREMENTS AND MAIN RESULTS Pain intensity was evaluated with a 101-point numerical rating scale . Blood pressure , heart rate ( HR ) , respiratory rate , arterial hemoglobin oxygen saturation , and any side effects were recorded . There were no significant differences between the clonidine and control groups with respect to postoperative pain . The patients in the clonidine group required a total meperidine dose of 62.7 + /- 4.9 mg , compared with 70.4 + /- 3.9 mg in the control group ( mean + /- SEM ; not a significant difference ) . Systolic blood pressure and HR were significantly lower from 20 to 120 minutes and from 30 to 120 minutes , respectively after the start of the clonidine infusion compared with the placebo . No patient had to be treated for hypotension or bradycardia . Serious side effects were not observed . CONCLUSIONS During the first 2 postoperative hours following cholecystectomy , postoperative meperidine intake could not be reduced by IV administration of clonidine 300 micrograms", "In a double‐blind , placebo‐controlled study in 125 patients undergoing a cholecystectomy , a comparison was made of the quality of post‐operative pain relief during ‘ patient‐controlled ’ intake of sublingual buprenorphine in combination with either rectally administered naproxen 1000 mg/24 h , paracetamol 4000 mg/24 h or a placebo . Results obtained in 97 patients were analysed . Five of these patients needed a rescue medication with morphine hydrochloride intramuscularly because of insufficient pain relief or because of nausea and vomiting . The quality of pain relief , as measured on a four‐point scale , was comparable in all three groups throughout the study period and no significant differences became apparent . Only on the day of surgery ( day 0 ) was intake of buprenorphine significantly greater in the placebo group ( 2.3 tablets/24 h ) than in the naproxen and paracetamol groups ( 1.8 and 1.5 tablets/24 h , respectively ) . It is concluded that after cholecystectomy ‘ patient‐controlled ’ intake of sublingual buprenorphine as a sole agent provides acceptable pain relief in about 80 % of patients . More elaborate methods , such as intravenous patient‐controlled analgesia , might be necessary to achieve good pain relief in the remainder of these patients", "Although postoperative pain has been reduced significantly since the advent of laparoscopic surgery , many patients still complain of moderate abdominal and shoulder pain during the first 48 to 72 h after surgery . In this study , the effect of subdiaphragmatic instillation of bupivacaine after laparoscopic cholecystectomy was investigated . The evaluation of postoperative pain was done according to a numerical verbal scale and the dose of analgesia required . The results showed a considerable reduction of postoperative pain during the first 48 h after surgery in patients who received bupivacaine instillation . Although the literature shows certain controversy as to the effects of similar methods , our study concludes that instillation of a long-acting anesthetic , such as bupivacaine , into the subdiaphragmatic space after laparoscopic procedures is effective in postoperative pain reduction", "Background The factors affecting cardiorespiratory changes and postoperative pain after laparoscopic cholecystectomy are poorly understood . The aim of this study was to assess these changes in patients undergoing laparoscopic cholecystectomy at an insufflation pressure of 7.5 or 15 mmHg", " The aim of this study was to determine whether injection of a long‐acting local anaesthetic , in relation to the port sites at the level of the parietal peritoneum , would reduce postoperative pain following laparoscopic cholecystectomy . Patients were entered into a r and omized , prospect i ve , double‐blind study comparing the effects of a st and ard technique , in which bupivacaine ( total of 20 ml , 0–5 per cent ) was injected into the subcutaneous periportal tissue around the four port sites , and a technique in which bupivacaine ( total of 20 ml , 0.25 per cent ) was injected into the subcutaneous periportal tissue as above with the addition of periportal parietal peritoneal injection of bupivacaine ( total of 20 ml , 0–25 per cent ) . Two scores for pain , with the patient at rest , and on movement , were assessed 6 and 18 h after surgery using a visual analogue pain scale . Median pain score was significantly higher in patients who received st and ard technique ( n = 40 ) than in those given peritoneal injection ( n = 40 ) at both 6 ( rest = 3.0 versus 1.0 , movement = 5.0 versus 2.9 ) and 18 h ( rest = 1.9 versus 0 , movement = 3.2 versus 1.2 ) . Both opiate and oral analgesic requirements were reduced in patients administered peritoneal injection , although this was not statistically significant . The addition of periportal injection of bupivacaine at the level of the parietal peritoneum , performed under direct vision , reduces pain after laparoscopic cholecystectomy", "STUDY OBJECTIVE To assess the anesthetic effects of clonidine during sevoflurane anesthesia guided by the bispectral index ( BIS ) , which is a processed EEG variable correlated with anesthetic-hypnotic depth . DESIGN Placebo-controlled , double-blind clinical trial . SETTING S Elective laparoscopic surgery . PATIENTS 60 ASA physical status I patients scheduled for laparoscopic surgery . INTERVENTIONS Patients received either clonidine ( 3 micrograms/kg , 15 min before induction ) or placebo premedication for a sevoflurane-induced and sevoflurane-maintained anesthesia . Sevoflurane was titrated against a BIS held between 40 and 50 . Analgesia was provided by local infiltration with bupivacaine . Need for postoperative analgesia was recorded . RESULTS AND CONCLUSION Mean sevoflurane requirements were not lower with clonidine pretreatment . There was statistically better perioperative hemodynamic stability ( i.e. , fewer episodes of hypertension and tachycardia ) without clinical relevance . A decreased need for postoperative analgesia was observed", "In the current study , 55 patients undergoing elective cholecystectomy were r and omly allocated to receive postoperative analgesia ( morphine sulfate ) administered through either patient-controlled intravenous ( PCA ) or st and ard intramuscular ( IM ) routes . There were no significant differences in length of hospitalization or required dose of morphine sulfate . Patients r and omized to PCA reported significantly improved subjective relief from pain and a smaller percentage of time in pain during each of the first two postoperative days . In addition , they reported less sedation and less interference with both postoperative breathing and pulmonary recovery than patients who received IM morphine . Theoretically , PCA regimens can deliver narcotic analgesia at a higher and more varied rate ( with fewer side effects ) compared with st and ard IM narcotic delivery , which is more limited by considerations of clinical doses . In PCA dosing , patients should experience less time in pain and sedation . The results of the current study support this premise", "In a double-blind r and omized trial , 50 patients scheduled for elective cholecystectomy received 50 mL of either 0.25 % bupivacaine hydrochloride or physiologic saline by wound perfusion at the end of the operation before wound closure . The duration of incisional infiltration , total amount of postoperative analgesics administered , and total hospital stay were recorded . Pulmonary function tests were performed the day before surgery and 1 day after surgery . There was no difference between the two groups with regard to duration of analgesia , the amount of analgesics administered , or the total hospital stay . Both groups also had similar decrements in forced vital capacity and forced expiratory volume on the first postoperative day . We conclude that wound infiltration with 0.25 % bupivacaine after elective cholecystectomy is not effective in reducing postoperative pain . Lung function disturbances can not be prevented", "BACKGROUND Successful management of postoperative pain requires that adequate analgesia is achieved without excessive adverse effects . Opioid-induced nausea and vomiting is known to impair patients ' satisfaction , but there are no studies providing sufficient power to test the hypothesis that the incidence of opioid-induced nausea and vomiting differs between micro -opioid receptor agonists . Thus , we tested the hypothesis that the incidence of vomiting and nausea differs between morphine and piritramide . METHODS In a prospect i ve , r and omized , double-blind fashion , we administered either morphine ( n=250 ) or piritramide ( n=250 ) by patient-controlled analgesia ( PCA ) for postoperative pain relief . We used a bolus dose of 1.5 mg with a lockout time of 10 min . Incidence and intensity ( numerical rating scale ) of postoperative nausea , vomiting , pain , patient satisfaction ( score 0 - 10 ) , side-effects ( score 0 - 3 ) and drug consumption were measured . RESULTS Mean drug consumption did not differ between the piritramide and morphine groups ( 30.8 ( SD 22.4 ) mg day(-1 ) vs 28.4 ( 21.8 ) mg day(-1 ) ) during the first postoperative day and there were no significant differences in the overall incidence of nausea ( 30 % vs 27 % ) and vomiting ( 19 % vs 15 % ) . Intensity of nausea correlated inversely ( P=0.01 ) with morphine consumption but not with piritramide consumption . Pain scores both at rest ( 2.2 ( 1.9 ) vs 2.6 ( 2 ) ) and during movement ( 4.4 ( 2.2 ) vs 4.9 ( 2.3 ) ) were slightly but significantly less with morphine . CONCLUSIONS Opioid-induced emesis was observed in about one-third of the patients using morphine and piritramide for PCA and the incidence of vomiting was one-half of that . Potential differences in the incidence of vomiting during PCA therapy between these micro-opioid receptor agonists can be excluded", "Several studies have reported the feasibility of using ‘ needlescopic ’ instruments with a diameter less than 3 mm in minimally invasive surgery . This study reports a comparison of needlescopic cholecystectomy and laparoscopic cholecystectomy", "Objective : To determine the effects of preoperative dexamethasone on surgical outcome after laparoscopic cholecystectomy ( LC ) . Summary Background Data : Pain and fatigue are dominating symptoms after LC and may prolong convalescence . Methods : In a double-blind , placebo-controlled study , 88 patients were r and omized to intravenous dexamethasone ( 8 mg ) or placebo 90 minutes before LC . Patients received a similar st and ardized anesthetic , surgical , and multimodal analgesic treatment . All patients were recommended 2 days postoperative duration of convalescence . The primary endpoints were fatigue and pain . Preoperatively and at several times during the first 24 postoperative hours , we measured C-reactive protein ( CRP ) and pulmonary function , pain scores , nausea , and number of vomiting episodes were registered . Analgesic and antiemetic requirements were recorded . Also , on a daily basis , patients reported scores of fatigue and pain before and during the first postoperative week and the date s for resumption of work and recreational activities . Results : Eight patients were excluded from the study , leaving 40 patients in each study group for analysis . There were no apparent side effects of the study drug . Dexamethasone significantly reduced postoperative levels of CRP ( P = 0.01 ) , fatigue ( P = 0.01 ) , overall pain , and incisional pain during the first 24 postoperative hours ( P total requirements of opioids ( P overall and visceral pain scores during the first postoperative week were significantly reduced ( P Dexamethasone also reduced nausea and vomiting on the day of operation ( P Resumption of recreational activities was significantly faster in the dexamethasone group versus placebo group ( median 1 day versus 2 days ) ( P dexamethasone ( 8 mg ) reduced pain , fatigue , nausea and vomiting , and duration of convalescence in patients undergoing noncomplicated LC , when compared with placebo , and is recommended for routine use", "Laparoscopic cholecystectomy is the surgical treatment of choice for symptomatic gallstones . Nonsteroidal antiinflammatory drugs offer effective analgesia , avoiding the central side effects of opiate drugs . To assess intramuscular diclofenac sodium ( Voltarol ; Ciba-Geigy ) after laparoscopic cholecystectomy , 55 consecutive patients ( 41 female ; 14 male ; mean age : 50 years ) were r and omised to receive either diclofenac or placebo in double-blind fashion . Six patients were withdrawn from study ( three conversions to open cholecystectomy ; three incomplete documentation ) . Pain scores were assessed at 4 , 24 , and 48 h using a linear analogue scale ; opiate consumption and time to first oral fluid and food were recorded . In 26 patients receiving diclofenac , median scores at 4 h were 1.6 ( range 0 - 7.6 ) as compared with 4.1 ( range 0 - 7.6 ) in 23 control patients ( p = 0.05 , 95 % confidence limits 3.2 , 0 ; Mann-Whitney U test ) . Nausea scores , return to diet , and time to discharge did not differ significantly between the groups . Intramuscular diclofenac significantly reduces early postoperative pain after laparoscopic cholecystectomy and is worthy of consideration if the procedure were ever undertaken as day case surgery", "Since it has been suggested that the use of nitrous oxide ( N2O ) may contribute to bowel distention , we evaluated the effects of N2O on operating conditions during laparoscopic cholecystectomy in 50 healthy patients using a double-blind protocol design . All patients received the same preanesthetic medication ( midazolam , 2 mg intravenously ) and induction of anesthesia consisted of intravenously administered fentanyl 1.5 micrograms.kg-1 , thiopental 4 - 6 mg.kg-1 , and a nondepolarizing muscle relaxant . For maintenance of anesthesia , patients were r and omly assigned to one of two treatment groups : group 1 ( n = 26 ) received isoflurane with 70 % N2O in oxygen ( O2 ) , whereas group 2 ( n = 24 ) received isoflurane in an air/O2 mixture . The surgeon ( blinded to the anesthetic technique ) estimated the degree of technical difficulty before beginning the operation using a five-point scale . At 15-min intervals throughout the operation , the surgeon was asked to evaluate both \" overall operating conditions \" and degree of \" bowel distension \" using independent five-point scales . At the end of the operation , the surgeon was asked whether or not N2O had been used as part of the anesthetic technique . There were no significant intraoperative differences between the two groups with respect to operating conditions or bowel distension . More importantly , there was no time-related change in either variable during the course of the operation . Finally , the incidence of postoperative nausea and vomiting was similar in both treatment groups . The surgeon was able to correctly determine that N2O had been administered only 44 % of the time . Thus , N2O had no clinical ly apparent deleterious effects during laparoscopic cholecystectomy" ]	41184398-06ff-11f0-808a-c43d1ab1c353
Background Self-reported disability has a strong negative impact on older people ’s quality of life and is often associated with the need for assistance and health care services . Resistance training ( RT ) has been repeatedly shown to improve muscle function ( e.g. strength ) and functional capacity ( e.g. gait speed , chair-rise ) in older adults with functional limitations . Nevertheless , it is unclear whether such objective ly assessed improvements translate into a reduction in self-reported disability . Objectives To assess : i ) whether and to what extent RT interventions have an effect on self-reported disability in older adults ( ≥65 years ) with functional limitations or disability ; and ii ) whether the effects on self-reported disability are associated with changes in objective measures of muscle strength and functional capacity across studies . Methods PubMed , Embase , Web of Science , CINAHL and SPORTD iscus electronic data bases were search ed in June 2018 . R and omized controlled trials reporting effects of RT on self-reported disability/function in ≥65 year-old adults with defined , functional limitations or self-reported disability were eligible . Data on self-reported disability/function were pooled by calculating adjusted st and ardized mean differences ( SMD ) using Hedges’g . Likewise , effect sizes for three secondary outcomes : knee extensor muscle strength ; gait capacity ; and lower body functional capacity were calculated and fit as covariates in separate meta-regressions with self-reported disability as the dependent factor . Results Fourteen RCTs were eligible for the primary meta- analysis on self-reported disability . The total number of participants was 651 ( intervention n = 354 ; control n = 297 ) . A significant moderate positive effect of RT was found ( SMD : 0.59 , 95 % CI : 0.253 to 0.925 , p = 0.001 ) . Between- study heterogeneity was present ( I2 statistic = 75,1 % , p ) . RT effects on objective measures of lower body functional capacity were significantly associated with effects on self-reported disability ( Adj . R2 = 99 % , p = 0.002 , n = 12 studies ) , whereas no significant associations with gait capacity or knee extensor strength were found . Conclusions This review provides evidence that RT has a moderate positive effect on self-reported disability/function in old people with or at risk for disability . The effects are strongly associated with effects on objective measures of lower body functional capacity	[ "PURPOSE We evaluated the value of resistance training on measures of physical performance in disabled older women with coronary heart disease ( CHD ) . METHODS The study intervention consisted of a 6-month program of resistance training in a r and omized controlled trial format . Training intensity was at 80 % of the single-repetition maximal lift . Control patients performed light yoga and breathing exercises . Study participants included 42 women with CHD , all > or= 65 yr of age and community dwelling . Subjects were screened by question naire to have low self-reported physical function . The primary study measurements related to the performance of 16 household activities of the Continuous Scale Physical Functional Performance test ( CSPFP ) . These ranged from dressing , to kitchen and cleaning activities , to carrying groceries and walking onto a bus with luggage , and a 6-min walk . Activities were measured in time to complete a task , weight carried during a task , or distance walked . Other measures included body composition , measures of aerobic fitness and strength , and question naire-based measures of physical function and depression score . RESULTS Study groups were similar at baseline by age , aerobic capacity , strength , body composition , and in performing the CSPFP . After conditioning , 13 of 16 measured activities were performed more rapidly , or with increased weight carried , compared with the control group ( all P Maximal power for activities that involved weight-bearing over a distance , increased by 40 % ( P Disabled older women with CHD who participate in an intense resistance-training program improve physical capacity over a wide range of household physical activities . Benefits extend beyond strength-related activities , as endurance , balance , coordination , and flexibility all improved . Strength training should be considered an important component in the rehabilitation of older women with CHD", "& NA ; Physical therapists seeking to use evidence to guide their practice may have limited time to read research reports . One way to reduce the time required to identify and read about the research that is relevant to a particular clinical question is to read a systematic review that summarizes multiple studies . This paper explains the process that is used to conduct systematic review s , which includes the establishment of a protocol , comprehensive search ing , appraisal of the quality of the included studies , data extraction and meta analysis , and consideration of the clinical and research implication s of the findings . We also consider how the reader of a systematic review can determine whether the review is likely to provide an unbiased ( believable ) estimate of the treatment effect . A systematic review of r and omized trials of a cardiopulmonary physical therapy intervention is used as an example . The issue of appraisal of quality is then discussed further , with a demonstration of how one vali date d tool for quality appraisal ‐‐the PEDro scale‐‐can be used to evaluate a r and omized trial in cardiopulmonary physical therapy", "BACKGROUND Falls prevention is an international priority , and residents of long-term aged care fall approximately 3 times more often than community dwellers . There is a relative scarcity of published trials in this setting . OBJECTIVES Our objective was to undertake a r and omized controlled trial to test the effect of published best practice exercise in long-term residential aged care . The trial was design ed to determine if combined high level balance and moderate intensity progressive resistance training ( the Sunbeam Program ) is effective in reducing the rate of falls in residents of aged care facilities . METHOD A cluster r and omized controlled trial of 16 residential aged care facilities and 221 participants was conducted . The broad inclusion criterion was permanent residents of aged care . Exclusions were diagnosed terminal illness , no medical clearance , permanent bed- or wheelchair-bound status , advanced Parkinson 's disease , or insufficient cognition to participate in group exercise . Assessment s were taken at baseline , after intervention , and at 12 months . R and omization was performed by computer-generated sequence to receive either the Sunbeam program or usual care . A cluster refers to an aged care facility . INTERVENTION The program consisted of individually prescribed progressive resistance training plus balance exercise performed in a group setting for 50 hours over a 25-week period , followed by a maintenance period for 6 months . OUTCOME MEASURES The primary outcome measure was the rate of falls ( number of falls and days followed up ) . Secondary outcomes included physical performance ( Short Physical Performance Battery ) , quality of life ( 36-item Short-Form Health Survey ) , functional mobility ( University of Alabama Life Space Assessment ) , fear of falling ( Falls Efficacy Scale International ) , and cognition ( Addenbrooke 's Cognitive Evaluation-revised ) . RESULTS The rate of falls was reduced by 55 % in the exercise group ( incidence rate ratio = 0.45 , 95 % confidence interval 0.17 - 0.74 ) ; an improvement was also seen in physical performance ( P = .02 ) . There were no serious adverse events . CONCLUSION The Sunbeam Program significantly reduced the rate of falls and improved physical performance in residents of aged care . This finding is important as prior work in this setting has returned inconsistent outcomes , result ing in best practice guidelines being cautious about recommending exercise in this setting . This work provides an opportunity to improve clinical practice and health outcomes for long-term care residents", "Frailty has emerged as an important risk factor for disability . Age-related declines in physical and physiological function lead to increased risk of loss of independence and poor quality of life . Recent evidence has shown the effectiveness of physical exercise programmes in preventing or reversing frailty . The aim of this study was to evaluate changes in the functioning of frail elderly individuals after undergoing resistance training for 3 days a week for 8 weeks . The effectiveness of exercise training was investigated in 48 frail elderly individuals who were r and omly assigned to the following intervention groups : high-intensity ( HI ; n=16 ; age : 69–96 years ) or low-intensity ( LI ; n=16 ; age : 77–93 years ) strength training groups or a control group ( n=16 ; age : 76–93 years ) with no specific exercise programme . Participants were assessed for muscle strength , physical function , activities of daily living , depression and quality of life . The HI group had significantly better results ( P Short Physical Performance Test than the LI group ; however , the LI group did show a significant improvement in those scores , whereas the scores of the control group worsened . Results for the other evaluations were similarly favourable in both exercise groups ( P>0.05 ) . The study showed that LI exercise was as effective as HI exercise for most parameters tested . Exercise training is useful for the prevention or treatment of frailty , as it improves functioning by contributing positively to muscle strength , gait , balance and quality of life", "The goal of this study was to determinate the effects of physical training in older adults with mobility limitations . Thirty frail women ( 84 ± 6 years ) were r and omly assigned to a training or control group for 12 weeks of upper body physical training ( UBT ) performed sitting on wheelchairs . Trained subjects showed a significant improvement in arms strength ( + 29 % ) , and shoulder flexibility ( + 10 cm ) but did not improve in arms circumference . The activities of daily living ( ADLs ) were improved ( + 77 % ) , cognitive function as defined by the Mini-Mental State Examination ( MMSE ) was maintained in the trained group ( + 3 % ) and declined in the control group ( −21 % ) . These results demonstrate that UBT in dependent older women with mobility limitations can increase strength and improve ADLs", " Eighty-six elderly people with limited mobility and dependence in at least one activity of daily living were recruited to a home exercise study . The subjects ( mean age 82 years ) were allocated at r and om to either a strength exercise group , a mobility exercise group or a health education group . Subjects were visited for 30 minutes every 3 - 4 weeks by a physiotherapist who gave both verbal and written instruction . Sixty-nine of the original 86 completed the 6-month study , with five drop-outs from the strength group , ten drop-outs from the mobility group , and two drop-outs from the health education group . By the end of the study , there were no significant differences between the groups with regard to changes in outcome variables . The results showed a trend towards improvement in both the exercise groups in both Sit to St and and Timed Get Up and Go tests , but this failed to attain statistical significance . Further work is required to identify the optimal exercise intervention for this subgroup of the elderly population", "CONTEXT Hip fractures are common in the elderly , and despite st and ard rehabilitation , many patients fail to regain their prefracture ambulatory or functional status . OBJECTIVE To determine whether extended outpatient rehabilitation that includes progressive resistance training improves physical function and reduces disability compared with low-intensity home exercise among physically frail elderly patients with hip fracture . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted between August 1998 and May 2003 among 90 community-dwelling women and men aged 65 years or older who had had surgical repair of a proximal femur fracture no more than 16 weeks prior and had completed st and ard physical therapy . INTERVENTION Participants were r and omly assigned to 6 months of either supervised physical therapy and exercise training ( n = 46 ) or home exercise ( control condition ; n = 44 ) . MAIN OUTCOME MEASURES Primary outcome measures were total scores on a modified Physical Performance Test ( PPT ) , the Functional Status Question naire physical function subscale ( FSQ ) , and activities of daily living scales . Secondary outcome measures were st and ardized measures of skeletal muscle strength , gait , balance , quality of life , and body composition . Participants were evaluated at baseline , 3 months , and 6 months . RESULTS Changes over time in the PPT and FSQ scores favored the physical therapy group ( P = .003 and P = .01 , respectively ) . Mean change ( SD ) in PPT score for physical therapy was + 6.5 ( 5.5 ) points ( 95 % confidence interval [ CI ] , 4.6 - 8.3 ) , and for the control condition was + 2.5 ( 3.7 ) points ( 95 % CI , 1.4 - 3.6 points ) . Mean change ( SD ) in FSQ score for physical therapy was + 5.2 ( 5.4 ) points ( 95 % CI , 3.5 - 6.9 ) and for the control condition was + 2.9 ( 3.8 ) points ( 95 % CI , 1.7 - 4.0 ) . Physical therapy also had significantly greater improvements than the control condition in measures of muscle strength , walking speed , balance , and perceived health but not bone mineral density or fat-free mass . CONCLUSION In community-dwelling frail elderly patients with hip fracture , 6 months of extended outpatient rehabilitation that includes progressive resistance training can improve physical function and quality of life and reduce disability compared with low-intensity home exercise", "This r and omized controlled trial examined the effects of multicomponent training on muscle power output , muscle mass , and muscle tissue attenuation ; the risk of falls ; and functional outcomes in frail nonagenarians . Twenty-four elderly ( 91.9 ± 4.1 years old ) were r and omized into intervention or control group . The intervention group performed a twice-weekly , 12-week multicomponent exercise program composed of muscle power training ( 8–10 repetitions , 40–60 % of the one-repetition maximum ) combined with balance and gait retraining . Strength and power tests were performed on the upper and lower limbs . Gait velocity was assessed using the 5-m habitual gait and the time-up- and -go ( TUG ) tests with and without dual-task performance . Balance was assessed using the FICSIT-4 tests . The ability to rise from a chair test was assessed , and data on the incidence and risk of falls were assessed using question naires . Functional status was assessed before measurements with the Barthel Index . Midthigh lower extremity muscle mass and muscle fat infiltration were assessed using computed tomography . The intervention group showed significantly improved TUG with single and dual tasks , rise from a chair and balance performance ( P and a reduced incidence of falls . In addition , the intervention group showed enhanced muscle power and strength ( P the total and high-density muscle cross-sectional area in the intervention group . The control group significantly reduced strength and functional outcomes . Routine multicomponent exercise intervention should be prescribed to nonagenarians because overall physical outcomes are improved in this population", "Objectives To determine whether a lifestyle integrated approach to balance and strength training is effective in reducing the rate of falls in older , high risk people living at home . Design Three arm , r and omised parallel trial ; assessment s at baseline and after six and 12 months . R and omisation done by computer generated r and om blocks , stratified by sex and fall history and concealed by an independent secure website . Setting Residents in metropolitan Sydney , Australia . Participants Participants aged 70 years or older who had two or more falls or one injurious fall in past 12 months , recruited from Veteran ’s Affairs data bases and general practice data bases . Exclusion criteria were moderate to severe cognitive problems , inability to ambulate independently , neurological conditions that severely influenced gait and mobility , resident in a nursing home or hostel , or any unstable or terminal illness that would affect ability to do exercises . Interventions Three home based interventions : Lifestyle integrated Functional Exercise ( LiFE ) approach ( n=107 ; taught principles of balance and strength training and integrated selected activities into everyday routines ) , structured programme ( n=105 ; exercises for balance and lower limb strength , done three times a week ) , sham control programme ( n=105 ; gentle exercise ) . LiFE and structured groups received five sessions with two booster visits and two phone calls ; controls received three home visits and six phone calls . Assessment s made at baseline and after six and 12 months . Main outcome measures Primary measure : rate of falls over 12 months , collected by self report . Secondary measures : static and dynamic balance ; ankle , knee and hip strength ; balance self efficacy ; daily living activities ; participation ; habitual physical activity ; quality of life ; energy expenditure ; body mass index ; and fat free mass . Results After 12 months ’ follow-up , we recorded 172 , 193 , and 224 falls in the LiFE , structured exercise , and control groups , respectively . The overall incidence of falls in the LiFE programme was 1.66 per person years , compared with 1.90 in the structured programme and 2.28 in the control group . We saw a significant reduction of 31 % in the rate of falls for the LiFE programme compared with controls ( incidence rate ratio 0.69 ( 95 % confidence interval 0.48 to 0.99 ) ) ; the corresponding difference between the structured group and controls was non-significant ( 0.81 ( 0.56 to 1.17 ) ) . Static balance on an eight level hierarchy scale , ankle strength , function , and participation were significantly better in the LiFE group than in controls . LiFE and structured groups had a significant and moderate improvement in dynamic balance , compared with controls . Conclusions The LiFE programme provides an alternative to traditional exercise to consider for fall prevention . Functional based exercise should be a focus for interventions to protect older , high risk people from falling and to improve and maintain functional capacity . Trial registration Australia and New Zeal and Clinical Trials Registry 12606000025538", "BACKGROUND The purpose of this efficacy study was to measure the dose-response effect of a free weight-based resistance training program by comparing the effects of two training intensities ( low-moderate and high ) of the knee extensor ( KE ) muscles on muscle function , functional limitations , and self-reported disability . METHODS The authors conducted a single-blinded , r and omized , placebo-controlled trial . Twenty-two institutionalized elders ( mean age , 81.5 years ) were assigned to either high-intensity strength training ( HI ; n = 8) , low-moderate intensity strength training ( LI ; n = 6 ) , or weight-free placebo-control training ( PC ; n = 8) . The HI group trained at 80 % of their 1-repetition maximum and the LI group trained at 40 % . All groups performed 3 sets of 8 repetitions , 3 times per week for 10 weeks . Outcome measures included KE maximal strength , KE endurance , and functional performance as assessed by 6-minute walking , chair-rising , and stair-climbing tests , and by self-reported disability . RESULTS KE strength and endurance , stair-climbing power , and chair-rising time improved significantly in the HI and LI groups compared with the PC group . Six-minute walking distance improved significantly in the HI group but not in the LI group compared with the PC group . Changes observed in HI were significantly different from those observed in the LI group for KE strength and endurance and the 6-minute walking test , with a trend in the same direction for chair-rising and stair-climbing . Changes in strength were significantly related to changes in functional outcomes , explaining 37 % to 61 % of the variance . CONCLUSIONS These results show strong dose-response relationships between resistance training intensity and strength gains , and between strength gains and functional improvements after resistance training . Low-moderate intensity resistance training of the KE muscles may not be sufficiently robust from a physiologic perspective to achieve optimal improvement of functional performance . Supervised HI , free weight-based training for frail elders appears to be as safe as lower intensity training but is more effective physiologically and functionally", "BACKGROUND The study tested the effect of strength and endurance training on gait , balance , physical health status , fall risk , and health services use in older adults . METHODS The study was a single-blinded , r and omized controlled trial with intention-to-treat analysis . Adults ( n = 105 ) age 68 - 85 with at least mild deficits in strength and balance were selected from a r and om sample of enrollees in a health maintenance organization . The intervention was supervised exercise ( 1-h sessions , three per week , for 24 - 26 weeks ) , followed by self-supervised exercise . Exercise groups included strength training using weight machines ( n = 25 ) , endurance training using bicycles ( n = 25 ) , and strength and endurance training ( n = 25 ) . Study outcomes included gait tests , balance tests , physical health status measures , self-reported falls ( up to 25 months of follow-up ) , and inpatient and outpatient use and costs . RESULTS There were no effects of exercise on gait , balance , or physical health status . Exercise had a protective effect on risk of falling ( relative hazard = .53 , 95 % CI = .30-.91 ) . Between 7 and 18 months after r and omization , control subjects had more outpatient clinic visits ( p hospital costs over $ 5000 ( p Exercise may have beneficial effects on fall rates and health care use in some subgroups of older adults . In community-living adults with mainly mild impairments in gait , balance , and physical health status , short-term exercise may not have a restorative effect on these impairments", "The purpose of the study was to determine whether resistance training ( RT ) or a combination of resistance and aerobic training ( CT ) result ed in the most improvement in measures of functional ability in functionally limited elders . Elderly adults who exhibited some limits in functional ability were r and omly assigned to either a CT , RT , or control ( C ) group . Both RT and CT exercised three times per week for 16 weeks . At Weeks 0 and 17 , participants completed six measures of strength and six functional tests . A 3 ( group ) x 3 ( time ) ANOVA with repeated measures on the time factor was used to analyze the results . CT and RT scored significantly better than C at Week 17 for biceps curl , elbow extension , chair st and , and time up the stairs . These findings demonstrate that RT and CT are both effective at increasing measures of strength and functional ability in elderly adults who begin exercise with functional limitations", "Background : It has been unclear which training mode is most effective and feasible for improving physical performance in the risk group of prefrail community-dwelling older adults . Objective : The purpose of the present study was to compare the effects of strength training ( ST ) versus power training ( PT ) on functional performance in prefrail older adults . This study was registered at clinical trials.gov as NCT00783159 . Methods : 69 community-dwelling older adults ( > 65 years ) who were prefrail according to the definition of Fried were included in a 12-week exercise program . The participants were r and omized into an ST group , a PT group and a control group . All participants were supplemented with vitamin D3 orally before entering the intervention period . The primary outcome was the global score on the Short Physical Performance Battery ( SPPB ) . Secondary outcomes were muscle power , appendicular lean mass ( aLM ) measured by dual energy X-ray absorptiometry and self-reported functional deficits ( Short Form of the Late-Life Function and Disability Instrument , SF-LLFDI ) . Results : Regarding changes in the SPPB score during the intervention , significant heterogeneity between the groups was observed ( p = 0.023 ) . In pair-wise comparisons , participants in both training groups significantly ( PT : p = 0.012 , ST : 0.009 ) increased their SPPB score ( PT : Δmean = 0.8 , ST : Δmean = 1.0 ) compared to the control group , with no statistical difference among training groups ( p = 0.301 ) . No statistical differences were found in changes in aLM ( p = 0.769 ) , muscle power ( p = 0.308 ) and SF-LLFDI ( p = 0.623 ) between the groups . Muscle power significantly increased ( p = 0.017 ) under vitamin D3 intake . Conclusions : In prefrail community-dwelling adults , PT is not superior to ST , although both training modes result ed in significant improvements in physical performance . With regard to dropout rates , ST appears to be advantageous compared to PT . The high prevalence of vitamin D3 deficiency and the slight improvement of physical performance under vitamin D3 supplementation among study participants underline the relevance of this approach in physical exercise interventions ", "OBJECTIVES Although deficits in skeletal muscle strength , gait , balance , and oxygen uptake are potentially reversible causes of frailty , the efficacy of exercise in reversing frailty in community-dwelling older adults has not been proven . The aim of this study was to determine the effects of intensive exercise training ( ET ) on measures of physical frailty in older community-dwelling men and women . DESIGN R and omized controlled trial . SETTING Medical school research center . PARTICIPANTS One hundred fifteen sedentary men and women ( mean age + /- st and ard deviation = 83 + /- 4 ) with mild to moderate physical frailty , as defined by two of the following three criteria : Modified Physical Performance Test ( modified PPT ) score between 18 and 32 , peak oxygen uptake ( VO2 peak ) between 10 and 18 mL/kg/min , and self-report of difficulty or assistance with one basic activity of daily living ( ADL ) , or two instrumental ADLs . INTERVENTION Participants were r and omly assigned to a control group that performed a 9-month low-intensity home exercise program ( control ) or an exercise-training program ( ET ) . The control intervention primarily consisted of flexibility exercises . ET began with 3 months of flexibility , light-resistance , and balance training . During the next 3 months , resistance training was added , and , during the next 3 months , endurance training was added . MEASUREMENTS Modified PPT score , VO2 peak , performance of ADLs as measured by the Older Americans Re sources and Services instrument , and the Functional Status Question naire ( FSQ ) . RESULTS ET result ed in significantly greater improvements than home exercise in three of the four primary outcome measures . Adjusted 95 % confidence bounds on the magnitude of improvement in the ET group compared with the control group were 1.0 to 5.2 points for the modified PPT score , 0.9 to 3.6 mL/kg/min for VO2 peak , and 1.6 to 4.9 points for the FSQ score . CONCLUSIONS Our results show that intensive ET can improve measures of physical function and pre clinical disability in older adults who have impairments in physical performance and oxygen uptake and are not taking hormone replacement therapy better than a low-intensity home exercise program", "The purpose of the study was to compare the effects of three different types of group-based exercise programs ( resistance training , agility training and general stretching ) on back pain and health-related quality of life in older ( aged 75–85 years ) community-dwelling women with low bone mass ( i.e. , osteopenia or osteoporosis ) . The design was a 25-week r and omized controlled trial . Participating were 98 community-dwelling women with low bone mass between the ages of 75 to 85 years old . We assessed back pain and its related disability and health-related quality of life . All three types of group-based exercise programs significantly reduced back pain and its related disabilities , but only resistance and agility training significantly improved health-related quality of life in community-dwelling older women with low bone mass . Baseline physical activity level and class attendance were significant predictors of change in health-related quality of life . Change in back pain and its related disabilities after 25 weeks of exercise intervention was significantly correlated with change in health-related quality of life and changes in the domains of pain and physical function . Resistance and agility training significantly enhanced health-related quality of life and may have done so by increasing social interactions and support , enhancing self-efficacy of physical abilities and modifying the experience of back pain . These data provide valuable insight into the specifics of exercise prescription for older women with low bone mass . Future studies may wish to use individualized quality of life measures to further delineate the effects of different types of exercise on quality of life in older adults with low bone mass", "BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from \" fair \" to \" substantial , \" and the reliability of the total PEDro score was \" fair \" to \" good .", "Elderly participants experiencing difficulty in chair rising and with a maximum knee-extensor torque below 87.5 N . m were r and omized to different versions of a strength-training program for the knee-extensors : to a high-guidance group ( HG ; two group sessions supervised by a physical therapist and one unsupervised home session per week , n = 17 ) , a medium-guidance group ( MG ; one supervised group session and two unsupervised home sessions per week , n = 16 ) , or a control group ( C ; no exercise , n = 16 ) . Maximal isometric knee strength increased more in HG than in C ( p = .03 ) and with increasing guidance ( p = .03 ) . The effect was mainly the result of participants with low initial strength . Walking speed increased more for HG than for C ( p = .02 ) and than for MG ( p = .06 ) . No statistically significant improvements were seen on other functional tests . In summary , the study shows a trend toward better results with more supervision , but more and larger studies are needed to confirm this", "OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people", "Background and aims : An acute illness may place older frail people at increased risk of losing independence in functional abilities . Physical exercise may reduce the risk by improving muscle strength and balance . However , the effects of physical training on functional abilities have not been studied among frail , very old people recovering from an acute illness . The aim of this study was to determine the effects of a group-based exercise program on their ability to carry out self-care ( ADL ) and instrumental activities ( IADL ) relevant to daily life after discharge from hospital . Methods : This r and omized controlled trial examined 68 community-dwelling women aged 75 years or older ( mean age 83.0 , SD 3.9 ) who were hospitalized due to an acute illness , and were mobility-impaired at admission . Participants were recruited from the geriatric ward of a primary -care health-center hospital , and were r and omized into group-based strength training ( n=34 ) and control ( n=34 ) groups . The 10-week group-based intervention included strength training and functional exercises . The control group received instructions for a home exercise training program , including functional exercises but no further encouragement to exercise . The level of independence in ADL and IADL was evaluated , using a 13-item scale with stepwise grading from fully independent to fully dependent . Measurements took place immediately before and after the intervention , and three and nine months later . Results : The intervention did not have any significant main effect ( p=0.407 ) , nor was there any significant interaction between follow-up time and intervention ( p=0.854 ) . Conclusions : The multi-component outpatient strength training program did not improve autonomy in expert-evaluated ADL/IADL functions", "A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain . Potential trials were located by a computerised search supplemented with citation tracking . The method ological quality of the trials was assessed on 11 criteria and the level of evidence for each intervention was determined , based upon the amount , consistency and quality of evidence from the trials . The review located 13 trials that were generally of moderate quality . The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain", "BACKGROUND / OBJECTIVES To test the effects of Strong for Life ( SFL ) on the physical performance and self-rated health of older adults receiving Home and Community-Based Services ( HCBS ) . DESIGN R and omized , two-group trial with pre-post measures . SETTING In-home exercise program . PARTICIPANTS Clients aged 65 - 95 ( n=42 ) and their Home Care Aide ( HCA ) ( n=32 ) were r and omly assigned to a usual care and SFL intervention or usual care control group . INTERVENTION Clients were instructed in SFL by their HCA and completed SFL 3 times per week for 12-weeks . MEASUREMENTS Outcomes included grip and quadriceps strength , Timed Up and Go , gait speed , Self-Efficacy for Exercise , pain , and PROMIS-global health measured at baseline and immediately following the intervention . Clients completed opened ended survey items on SFL program evaluation . RESULTS Effect sizes were moderate for grip strength ( d= .38 ) , pain ( d= .34 ) , and PROMIS-global health ( d= .27 ) . Small effect sizes were found for all other measures . Median quadriceps and TUG scores differentially improved among intervention participants versus controls . No adverse health events and high program satisfaction were reported . Frailty prevalence in the control group increased between baseline and post-test while frailty prevalence in the intervention group decreased during the same time period . CONCLUSION Strong for Life has the potential to improve the strength , mobility , health , and frailty of older adults receiving HCBS . This study provides initial evidence of the impact of SFL for older adults receiving HCBS , as well as the safety of the intervention evidence d by the lack of reported adverse events", "BACKGROUND AND PURPOSE The majority of patients after a hip fracture do not return to prefracture functional status . Depression has been shown to affect recovery . Although exercise can reduce impairments , access issues limit elderly people from participating in facility-based programs . The primary purpose of this study was to determine the effects and feasibility of a home exercise program of moderate- or high-intensity exercise . A secondary purpose was to explore the relationship of depression and physical recovery . SUBJECTS Thirty-three elderly people ( 24 women , 9 men ; mean = 78.6 years of age , SD = 6.8 , range = 64 - 89 ) who had completed a regimen of physical therapy following hip fracture participated in the study . Subjects were r and omly assigned to a resistance training group , an aerobic training group , or a control group . METHODS Subjects were tested before and upon completion of the exercise trial . Isometric lower-extremity force , 6-minute-walk distance , free gait speed , mental status , and physical function were measured . Each exercise session was supervised by a physical therapist , and subjects received 20 visits over 12 weeks . The control group received biweekly mailings . The resistance training group performed 3 sets of 8 repetitions at the 8-repetition maximum intensity using a portable progressive resistance exercise machine . The aerobic training group performed activities that increased heart rate 65 % to 75 % of their age-predicted maximum for 20 continuous minutes . RESULTS Resistance and aerobic training were performed without apparent adverse effects , and adherence was 98 % . All groups improved in distance walked , force produced , gait speed , and physical function . Isometric force improved to a greater extent in the intervention groups than in the control group . Depressive symptoms interacted with treatment group in explaining the outcomes of 6-minute-walk distance and gait speed . DISCUSSION AND CONCLUSION High-intensity exercise performed in the home is feasible for people with hip fracture . Larger sample sizes may be necessary to determine whether the exercise regimen is effective in reducing impairments and improving function . Depression may play a role in the level of improvement attained", "OBJECTIVES To evaluate the short-term effects of three different resistance training programs , conducted at low intensity , on physical performance , muscle cross-sectional area ( CSA ) and the capacity to perform daily tasks in older adults living in a geriatric nursing home . DESIGN R and omized controlled trial , with a 4-month intervention period . SETTING A geriatric nursing home in Valencia , Spain . PARTICIPANTS Eighty-nine adults aged 75 to 96 who were independent in their daily activities . INTERVENTION After a baseline assessment , the participants were r and omly assigned to the control group or one of the three intervention groups : volitional contraction ( VC ; n=22 ) , neuromuscular electrical stimulation ( NMES ; n=22 ) , or neuromuscular electrical stimulation superimposed onto voluntary contractions ( NMES+ ; n=22 ) . The intervention focused on knee extension exercises and its intensity was set at 40 % of one-repetition maximum ( 1RM ) . MEASUREMENTS The primary outcome measure was mobility . Secondary outcomes were rectus femoris CSA , balance , aerobic endurance , upper-body strength and the capacity to perform daily tasks . All data were collected at baseline and after the 4-month intervention period . RESULTS The two-way ANOVA analysis showed a significant group × time interaction effect for the mobility ( P=.022 ) , rectus femoris CSA ( P=.001 ) , and the capacity to perform daily tasks ( P=.05 ) . The within-group analysis found a more prominent effect in the NMES+ group . Significant improvements were seen in rectus femoris CSA and the capacity to perform daily tasks in all intervention groups . Mobility only improved in the NMES+ group ( P=.026 ) . CONCLUSION From a short-term perspective , NMES+ exercise training , performed at low intensity , can improve physical performance , muscle CSA , and the capacity to perform daily activities , and to partially mitigate age-related consequences in older adults", "BACKGROUND Strength loss is strongly associated with functional decline and is reversible with exercise . The effect of increased strength on function has not been clearly established . The purpose of this study was to determine whether strength gain is associated with improvement in physical performance and disability . METHODS One hundred functionally impaired community-dwelling men and women ( 77.6 + /- 7.6 yrs ) were tested at baseline and outcome for lower extremity strength , physical performance , and disability . After r and om group assignment , exercise participants received strengthening exercises in their homes three times a week for 10 weeks while control subjects continued their normal activities . Using multiple regression techniques , the relationship between strength gain and improvement in physical performance and disability was assessed , controlling for age , depression , and baseline strength . RESULTS A significant impact of strength gain on mobility skills ( p = .0009 ) was found . The impact of strength gain on chair rise performance was significant in participants who were more impaired ( p = .04 ) . Strength gain was associated with gain in gait speed ( p = .02 ) and in falls efficacy ( p = .05 ) , but not with other balance , endurance , or disability measures . CONCLUSIONS Lower extremity strength gain is associated with gains in chair rise performance , gait speed , and in mobility tasks such as gait , transfers , stooping , and stair climbing , but not with improved endurance , balance , or disability . Strength gain is also associated with improvement in confidence in mobility . Factors that may influence the ability of strength gain to affect function are initial level of frailty and specificity of exercise . These results support the idea that strength training is an intervention that can potentially improve physical health status in many frail elders", "OBJECTIVE To evaluate the effectiveness of three different training protocol s on physical function of older adults living in long-term care facilities . Emphasis was placed on feasibility in real-life situations . METHODS Subjects ( N=224 ) were r and omised to 6 months of twice weekly ( 1 ) resistance training ; ( 2 ) all-round functional-skills training ; ( 3 ) a combination of both ; or ( 4 ) a control program . Fitness and performance measures and self-reported disability were measured at baseline and after 24 weeks intervention . RESULTS Attendance to the strength training was 76 % , to the functional-skills training 70 % and to the combined training 73 % . In those who attended at least 75 % of all classes ( n=97 ) the functional-skills and combined training program improved several fitness and performance measures compared to the control group . CONCLUSION Twice weekly functional-skills training , or a combination of resistance and functional-skills training can improve several fitness and performance measures of institutionalised older people . PRACTICE IMPLICATION S An important finding from our study was that less than twice a week exercise training is not enough for functional improvement , while it proved difficult for the elderly subjects to exercise twice weekly . Education on the health benefits of regular exercise , and a larger availability of classes in long-term care facilities may improve attendance" ]	4118441a-06ff-11f0-808a-c43d1ab1c353
Abstract Purpose As accurate and reproducible measurements of spinal curvature are crucial in the examination of patients with adolescent idiopathic scoliosis ( AIS ) , this systematic review aims to report on the reliability and validity of a range of inexpensive and easily administered anthropometric methods of postural asymmetry measurement in an AIS population , to inform practice in a clinical setting . Methods A systematic search of health research data bases located studies assessing reliability and validity of inexpensive and easily administered anthropometric measures . Results Fourteen studies satisfied eligibility criteria . The method ological quality of included studies ranged from low to high . Validity studies were of moderate to high quality . In total , nine clinical ly applicable , inexpensive and easily administered anthropometric methods were identified , for assessing AIS curvature . All methods demonstrated high to very high inter-observer and intra-observer reliability . Reported criterion validity of the scoliometer and 2D photographs , when compared to Cobb angle assessed from radiographs , ranged from low to very high . iPhone measurements correlated well with scoliometer measurements . 2D photography results had a moderate to high correlation with 3D topography results . Conclusions Overall , strong levels of evidence exist for iPhone and scoliometer measurements , with a high to very high reliability and moderate to very high validity . Moderate levels of evidence exist for scoliometer with mathematical formula and clinical examination with moderate and low validity , respectively . Limited evidence exists for aesthetic tools TRACE and AI and 2D photography . These results indicate there are accurate and reproducible anthropometric measures that are inexpensive and applicable in therapy setting s to assess postural asymmetry ; however , these only exist for measurement in the transverse plane , despite 3D characteristics of AIS . Further research is required into an inexpensive and easily administered method that can assess postural asymmetry in all anatomical planes	[ "OBJECTIVE To determine overall , test-retest and inter-rater reliability of posture indices among persons with idiopathic scoliosis . DESIGN A reliability study using two raters and two test sessions . SETTING Tertiary care paediatric centre . PARTICIPANTS Seventy participants aged between 10 and 20 years with different types of idiopathic scoliosis ( Cobb angle 15 to 60 ° ) were recruited from the scoliosis clinic . MAIN OUTCOME MEASURES Based on the XY co-ordinates of natural reference points ( e.g. , eyes ) as well as markers placed on several anatomical l and marks , 32 angular and linear posture indices taken from digital photographs in the st and ing position were calculated from a specially developed software program . Generalisability theory served to estimate the reliability and st and ard error of measurement ( SEM ) for the overall , test-retest and inter-rater design s. Bl and and Altman 's method was also used to document agreement between sessions and raters . RESULTS In the r and om design , dependability coefficients demonstrated a moderate level of reliability for six posture indices ( ϕ=0.51 to 0.72 ) and a good level of reliability for 26 posture indices out of 32 ( ϕ≥0.79 ) . Error attributable to marker placement was negligible for most indices . Limits of agreement and SEM values were larger for shoulder protraction , trunk list , Q angle , cervical lordosis and scoliosis angles . The most reproducible indices were waist angles and knee valgus and varus . CONCLUSIONS Posture can be assessed in a global fashion from photographs in persons with idiopathic scoliosis . Despite the good reliability of marker placement , other studies are needed to minimise measurement errors in order to provide a suitable tool for monitoring change in posture over time", "CONTEXT Previous long-term studies of idiopathic scoliosis have included patients with other etiologies , leading to the erroneous conclusion that all types of idiopathic scoliosis inevitably end in disability . Late-onset idiopathic scoliosis ( LIS ) is a distinct entity with a unique natural history . OBJECTIVE To present the outcomes related to health and function in untreated patients with LIS . DESIGN , SETTING , AND PATIENTS Prospect i ve natural history study performed at a midwestern university with outpatient evaluation of patients who presented between 1932 and 1948 . At 50-year follow-up , which began in 1992 , 117 untreated patients were compared with 62 age- and sex-matched volunteers . The patients ' mean age was 66 years ( range , 54 - 80 years ) . MAIN OUTCOME MEASURES Mortality , back pain , pulmonary symptoms , general function , depression , and body image . RESULTS The estimated probability of survival was approximately 0.55 ( 95 % confidence interval [ CI ] , 0.47 - 0.63 ) compared with 0.57 expected for the general population . There was no significant difference in the demographic characteristics of the 2 groups . Twenty-two ( 22 % ) of 98 patients complained of shortness of breath during everyday activities compared with 8 ( 15 % ) of 53 controls . An increased risk of shortness of breath was also associated with the combination of a Cobb angle greater than 80 degrees and a thoracic apex ( adjusted odds ratio , 9.75 ; 95 % CI , 1.15 - 82.98 ) . Sixty-six ( 61 % ) of 109 patients reported chronic back pain compared with 22 ( 35 % ) of 62 controls ( P = .003 ) . However , of those with pain , 48 ( 68 % ) of 71 patients and 12 ( 71 % ) of 17 controls reported only little or moderate back pain . CONCLUSIONS Untreated adults with LIS are productive and functional at a high level at 50-year follow-up . Untreated LIS causes little physical impairment other than back pain and cosmetic concerns", "Study Design : This was a prospect i ve blinded validity and reliability analysis . Objective : The aim of this study was validation and reliability evaluation of the Scoligauge iPhone app . Background : The scoliometer is used to clinical ly measure the rib hump in scoliosis as a means to evaluate the axial trunk rotation . The increasing availability of smartphone with built-in accelerometer led to the development of a vast number of applications to measure angles . Of these , the Scoligauge mimics a scoliometer . The aim of this study was to compare the validity of the Scoligauge iPhone application without an associated adapter with the traditional scoliometer and to test the reliability of the application in a clinical setting . Methods : Two observers measured the rib hump deformity on 34 consecutive patients with idiopathic scoliosis with an average Cobb angle of 24.2±13.5 degrees ( range , 4 to 65 degrees ) . Measurements were made with an iPhone without the adapter and with a scoliometer . The validity as well as the interobserver and intraobserver reliability were calculated using the intraclass coefficient ( ICC ) and the Bl and -Altman test . Results : The mean difference between the scoliometer and the Scoligauge application was 0.4 degrees [ 95 % confidence interval ( CI ) of ±3.1 degrees ] with an ICC of 0.947 ( P The intraobserver and interobserver ICC were 0.961 ( P The mean intraobserver difference was 0.0 degrees ( 95 % CI of ±2.7 degrees ) and the mean interobserver difference was 0.1 degrees ( 95 % CI of ±4.4 degrees ) . Conclusions : The intraobserver and interobserver reliability of the Scoligauge iPhone app , as well as its validity compared with the scoliometer , are excellent . The mean differences between measurements are small and clinical ly not significant . Thus , the Scoligauge application is valid for clinical evaluation even without special adapter . Level of Evidence : Level I ( Diagnostic Study )", "Background Screening tests play a significant role in rapid and reliable assessment of normal individual development in the entire population of children and adolescents . Body posture screening tests carried out at schools reveal that 50 - 60 % of children and adolescents demonstrate body posture abnormalities , with 10 % of this group at risk for progressive spinal deformities . This necessitates the search for effective and economically feasible forms of screening diagnosis . The aim of this study was to assess the reliability of clinical evaluation of body posture compared to objective assessment with the Zebris CMS-10 system ( Zebris Medical GmbH ) . Methods The study enrolled 13 - 15-year-old pupils attending a junior secondary school ( mean age 14.2 years ) . The study group consisted of 138 participants , including 71 girls and 67 boys , who underwent a clinical evaluation of the body posture and an examination with the Zebris CMS 10 system . Results Statistically significant discrepancies between the clinical and objective evaluation were noted with regard to lumbar lordosis in boys ( n = 67 ) and thoracic kyphosis in girls ( n = 71 ) . No statistically significant differences in both groups were noted for pelvic rotation and trunk position in the frontal plane . Conclusions 1 . The finding of significant discrepancies between the results of assessment in the sagittal plane obtained in the clinical examination and Zebris CMS-10-based assessment suggests that clinical evaluation should be used to provide a general estimation of accentuation or reduction of spinal curvatures in the sagittal plane.2 . The clinical evaluation of posture is reliable with regard to assessment in the frontal plane.3 . The Zebris CMS-10 system makes the clinical examination significantly more objective with regard to assessment of the physiological curvatures and may be used to make screening tests more objective with regard to detecting postural defects", "We did a prospect i ve study of 291 children and adolescents with idiopathic scoliosis to identify possible correlations between clinical ( scoliometer value , age , height ) and radiographic ( Cobb angle , Nash-Moe rotation , Risser iliac apophysis classification ) parameters to predict the curve angle . There was a statistically significant correlation between thoracic , thoracolumbar , and lumbar scoliometer values and the thoracic , thoracolumbar , and lumbar Cobb angles , respectively ( Pearson ’s r-0.685 , 0.572 , and 0.677 , respectively ) . There was a statistically significant correlation between Cobb angle in the thoracic , thoracolumbar , and lumbar spine and the patients ’ age and height . Mathematical formulas that predict the Cobb angle of thoracic , thoracolumbar , and lumbar scoliosis using the scoliometer measurements are reported", "Study Design A prospect i ve study was conducted in a young homogenous adolescent population , with the use of the scoliometer . Objectives To create a mathematic formula that provides the accurate Cobb angle of idiopathic scoliosis with the use of the scoliometer only . Summary of Background Data The scoliometer is an accepted method for detection and evaluation of scoliosis during screening programs . To the authors ' knowledge , there are no previous methods and formulas to estimate the approximate Cobb angle using only the scoliometer . Methods Several clinical ( scoliometer value , age , and sex ) and radiographic ( Cobb angle , Perdriolle of the apical vertebra , Risser iliac apophysis classification ) parameters from 442 ( 4.37 % ) of 10,109 screened adolescents who had a scoliometer value of at least 7 ° were taken and correlated using the simple and multiple linear regression analysis . Results Cobb angle and scoliometer value were statistically significantly correlated to each other . Two mathematic formulas were created to predict the Cobb angle of the thoracic and lumbar scoliosis , with similar sensitivity and accuracy . The thoracic and lumbar scoliometer values were statistic significantly correlated with the thoracic and lumbar Cobb angle ( P = 0.0254 and P = 0.0015 , respectively ) . The lumbar scoliometer value was significantly correlated with lumbar apical vertebra Perdriolle value . Also , the thoracic and lumbar Cobb angles were significantly correlated with thoracic and lumbar apical vertebra ( P = 0.0001 and P = 0.0015 , respectively ) . Conclusions In the present study , the authors have constructed two mathematic formulas , which provide accurately the scoliotic Cobb angle in young adolescents using only the scoliometer with a deviation of 5.63 ° for thoracic curves and 5.79 ° for lumbar curves . The authors recommend that all physicians engaged in scoliosis screening programs use the scoliometer based on the mathematic formulas that the authors developed . They believe that this method will reduce the cost of school screening programs , the overdiagnosis , and the unnecessary exposure to irradiation of this young population in the future", "BACKGROUND The complex skeletal deformations that accompany Idioapthic Scoliosis pose a challenge to the clinician to non-invasively discriminate Idiopathic Scoliosis patients from children with no pathology . Therefore , the focus of this study is to non-invasively evaluate the position and amplitude of displacement of the pelvis , shoulders and thorax during quiet st and ing of Idiopathic Scoliosis patients and control subjects . METHODS The quiet st and ing posture of 18 healthy adolescent females and 22 Idiopathic Scoliosis subjects was evaluated using an Optotrak 3020 position sensor over a period of 120 s , with 4 repeat trials . Outcome measures included the mean position , root mean square amplitude and range over the duration of 120 s trials for both linear and angular measures of the pelvis , thorax and shoulders . Appropriate sample times were chosen and evaluated for stability over the 120 s period , and between trial reliability was evaluated . FINDINGS There was a significant difference between groups for the mean position of the shoulder blade rotation in reference to the base of support and to the pelvis . The Idiopathic Scoliosis patients had a significantly larger root mean square amplitude of anterior-posterior displacement of the T1 and S1 spinous processes in reference to the base of support . There was no difference between the sample duration s to estimate the mean position of the body segments , however the root mean square increased significantly . INTERPRETATION This study demonstrates that postural abnormalities are evident during quiet st and ing in Idiopathic Scoliosis patients", "BACKGROUND CONTEXT Three-dimensional ( 3D ) deformations of the spine are predominantly characterized by two-dimensional ( 2D ) angulation measurements in coronal and sagittal planes , using anteroposterior and lateral X-ray images . For coronal curves , a method originally described by Cobb and for sagittal curves a modified Cobb method are most widely used in practice , and these methods have been shown to exhibit good-to-excellent reliability and reproducibility , carried out either manually or by computer-based tools . Recently , an ultralow radiation dose-integrated radioimaging solution was introduced with special software for realistic 3D visualization and parametric characterization of the spinal column . PURPOSE Comparison of accuracy , correlation of measurement values , intraobserver and interrater reliability of methods by conventional manual 2D and sterEOS 3D measurements in a routine clinical setting . STUDY DESIGN / SETTING Retrospective nonr and omized study of diagnostic X-ray images created as part of a routine clinical protocol of eligible patients examined at our clinic during a 30-month period between July 2007 and December 2009 . PATIENT SAMPLE In total , 201 individuals ( 170 females , 31 males ; mean age , 19.88 years ) including 10 healthy athletes with normal spine and patients with adolescent idiopathic scoliosis ( 175 cases ) , adult degenerative scoliosis ( 11 cases ) , and Scheuermann hyperkyphosis ( 5 cases ) . Overall range of coronal curves was between 2.4 ° and 117.5 ° . Analysis of accuracy and reliability of measurements were carried out on a group of all patients and in subgroups based on coronal plane deviation : 0 ° to 10 ° ( Group 1 , n=36 ) , 10 ° to 25 ° ( Group 2 , n=25 ) , 25 ° to 50 ° ( Group 3 , n=69 ) , 50 ° to 75 ° ( Group 4 , n=49 ) , and more than 75 ° ( Group 5 , n=22 ) . METHODS Coronal and sagittal curvature measurements were determined by three experienced examiners , using either traditional 2D methods or automatic measurements based on sterEOS 3D reconstructions . Manual measurements were performed three times , and sterEOS 3D reconstructions and automatic measurements were performed two times by each examiner . Means comparison t test , Pearson bivariate correlation analysis , reliability analysis by intraclass correlation coefficients for intraobserver reproducibility and interrater reliability were performed using SPSS v16.0 software ( IBM Corp. , Armonk , NY , USA ) . No funds were received in support of this work . No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this article . RESULTS In comparison with manual 2D methods , only small and nonsignificant differences were detectable in sterEOS 3D-based curvature data . Intraobserver reliability was excellent for both methods , and interrater reproducibility was consistently higher for sterEOS 3D methods that was found to be unaffected by the magnitude of coronal curves or sagittal plane deviations . CONCLUSIONS This is the first clinical report on EOS 2D/3D system ( EOS Imaging , Paris , France ) and its sterEOS 3D software , documenting an excellent capability for accurate , reliable , and reproducible spinal curvature measurements" ]	41184492-06ff-11f0-808a-c43d1ab1c353
Background Cash transfers and vouchers are forms of ‘ dem and -side financing ’ that have been widely used to promote maternal and newborn health in low- and middle-income countries during the last 15 years . Methods This systematic review consoli date s evidence from seven published systematic review s on the effects of different types of cash transfers and vouchers on the use and quality of maternity care services , and up date s the systematic search es to June 2015 using the Joanna Briggs Institute approach for systematic review ing . The review protocol for this up date was registered with PROSPERO ( CRD42015020637 ) . Results Data from 51 studies ( 15 more than previous review s ) and 22 cash transfer and voucher programmes suggest that approaches tied to service use ( either via payment conditionalities or vouchers for selected services ) can increase use of antenatal care , use of a skilled attendant at birth and in the case of vouchers , postnatal care too . The strongest evidence of positive effect was for conditional cash transfers and uptake of antenatal care , and for vouchers for maternity care services and birth with a skilled birth attendant . However , effects appear to be shaped by a complex set of social and healthcare system barriers and facilitators . Studies have typically focused on an initial programme period , usually two or three years after initiation , and many lack a counterfactual comparison with supply-side investment . There are few studies to indicate that programmes have led to improvements in quality of maternity care or maternal and newborn health outcomes . Conclusion Future research should use multiple intervention arms to compare cost-effectiveness with similar investment in public services , and should look beyond short- to medium-term service utilisation by examining programme costs , longer-term effects on service utilisation and health outcomes , and the equity of those effects	[ "OBJECTIVES To evaluate the impact of Oportunidades , a large-scale , conditional cash transfer programme in Mexico , on birthweight . The programme provides cash transfers to low-income , rural households in Mexico , conditional on accepting nutritional supplements health education , and health care . METHODS The primary analyses used retrospective reports from 840 women in poor rural communities participating in an effectiveness study and r and omly assigned to incorporation into the programme in 1998 or 1999 across seven Mexican states . Pregnant women in participating households received nutrition supplements and health care , and accepted cash transfers . Using multivariate and instrumental variable analyses , we estimated the impact of the programme on birthweight in grams and low birthweight ( 2500 g ) , receipt of any pre-natal care , and number of pre-natal visits . RESULTS Oportunidades beneficiary status was associated with 127.3 g higher birthweight among participating women and a 4.6 percentage point reduction in low birthweight . CONCLUSION The Oportunidades conditional cash transfer programme improved birthweight outcomes . This finding is relevant to countries implementing conditional cash transfer programmes ", "The maternal mortality ratio ( MMR ) in Ug and a has declined significantly during the last 20 years , but Ug and a is not on track to reach the millennium development goal of reducing MMR by 75 % by 2015 . More evidence on the cost-effectiveness of supply- and dem and -side financing programs to reduce maternal mortality could inform future strategies . This study analyses the cost-effectiveness of a voucher scheme ( VS ) combined with health system strengthening in rural Ug and a against the status quo . The VS , implemented in 2010 , provided vouchers for delivery services at public and private health facilities ( HF ) , as well as round-trip transportation provided by private sector workers ( bicycles or motorcycles generally ) . The VS was part of a quasi-experimental non-r and omized control trial . Improvements in institutional delivery coverage ( IDC ) rates can be estimated using a difference-in-difference impact evaluation method and the number of maternal lives saved is modelled using the evidence -based Lives Saved Tool . Costs were estimated from primary and secondary data . Results show that the dem and for births at HFs enrolled in the VS increased by 52.3 percentage points . Out of this value , conservative estimates indicate that at least 9.4 percentage points are new HF users . This 9.4 % bump in IDC implies 20 deaths averted , which is equivalent to 1356 disability-adjusted-life years ( DALYs ) averted . Cost-effectiveness analysis comparing the status quo and VS 's most conservative effectiveness estimates shows that the VS had an incremental cost-effectiveness ratio per DALY averted of US$ 302 and per death averted of US$ 20 756 . Although there are limitations in the data measures , a favourable cost-effectiveness ratio persists even under extreme assumptions . Dem and -side vouchers combined with supply-side financing programs can increase attended deliveries and reduce maternal mortality at a cost that is acceptable", "OBJECTIVES To evaluate the impact of Mexico 's conditional cash transfer programme on the quality of health care received by poor women . Quality is measured by maternal reports of prenatal care procedures received that correspond with clinical guidelines . METHODS The data describe retrospective reports of care received from 892 women in poor rural communities in seven Mexican states . The women were participating in an effectiveness study and r and omly assigned to incorporation into the programme in 1998 or 1999 . Eligible women accepted cash transfers conditional on obtaining health care and nutritional supplements , and participated in health education sessions . RESULTS Oportunidades beneficiaries received 12.2 % more prenatal procedures compared with non-beneficiaries ( adjusted mean 78.9 , 95 % Confidence Interval ( CI ) : 77.5 - 80.3 ; P Oportunidades conditional cash transfer programme is associated with better quality of prenatal care for low-income , rural women in Mexico . This result is probably a manifestation of the programme 's empowerment goal , by encouraging beneficiaries to be informed and active health consumers", "Objective To measure whether there was an association between the introduction of an output-based voucher programme and the odds of a facility-based delivery in two Nairobi informal settlements . Data sources Nairobi Urban Health and Demographic Surveillance System ( NUHDSS ) and two cross-sectional household surveys in Korogocho and Viw and ani informal settlements in 2004–05 and 2006–08 . Methods Odds of facility-based delivery were estimated before and after introduction of an output-based voucher . Supporting NUHDSS data were used to determine whether any trend in maternal health care was coincident with immunizations , a non-voucher outpatient service . As part of NUHDSS , households in Korogocho and Viw and ani reported place of delivery and the presence of a skilled birth attendant ( 2003–10 ) and vaccination coverage ( 2003–09 ) . A detailed maternal and child health ( MCH ) tool was added to NUHDSS ( September 2006–10 ) . Prospect i ve enrolment in NUHDSS-MCH was conditional on having a newborn after September 2006 . In addition to recording mother ’s place of delivery , NUHDSS-MCH recorded the use of the voucher . Findings There were significantly greater odds of a facility-based delivery among respondents during the voucher programme compared with similar respondents prior to voucher launch . Testing whether unrelated outpatient care also increased , a falsification exercise found no significant increase in immunizations for children 12–23 months of age in the same period . Although the proportion completing any antenatal care ( ANC ) visit remained above 95 % of all reported pregnancies and there was a significant increase in facility-based deliveries , the proportion of women completing 4 + ANC visits was significantly lower during the voucher programme . Conclusions A positive association was observed between vouchers and facility-based deliveries in Nairobi . Although there is a need for higher quality evidence and validation in future studies , this statistically significant and policy relevant finding suggests that increases in facility-based deliveries can be achieved through output-based finance models that target subsidies to underserved population", "Background Only 39 % of deliveries in Pakistan are attended by skilled birth attendants , while Pakistan 's target for skilled birth attendance by 2015 is > 90 % . Methods A 12-month maternal health voucher intervention was implemented in Dera Ghazi Khan City , located in Southern Punjab , Pakistan in 2009 . A pre-test/post-test non-experimental study was conducted to assess the impact of the intervention . Household interviews were conducted with r and omly selected women who delivered in 2008 ( the year prior to the voucher intervention ) , and with r and omly selected women who delivered in 2009 . A strong outreach model was used and voucher booklets valued at $ 50 , containing redeemable coupons for three antenatal care ( ANC ) visits , a postnatal care ( PNC ) visit and institutional delivery , were sold for $ 1.25 to low-income women targeted by project workers . Regression analysis was conducted to determine the impact of the voucher scheme on ANC , PNC , and institutional delivery . Marginal effects estimated from logistic regression analyses were used to assess the magnitude of the impact of the intervention . Results The women targeted by voucher outreach workers were poorer , less educated , and at higher parity . After adjusting for these differences , women who delivered in 2009 and were sold voucher booklets were significantly more likely than women who delivered in 2008 to make at least three ANC visits , deliver in a health facility , and make a postnatal visit . Purchase of a voucher booklet was associated with a 22 percentage point increase in ANC use , a 22 percentage point increase in institutional delivery , and a 35 percentage point increase in PNC use . Conclusions A voucher intervention implemented for 12 months was associated with a substantial increase in institutional delivery . A substantial scale-up of maternal health vouchers that focus on institutional delivery is likely to bring Pakistan closer to achieving its 2015 target for institutional delivery", "Background Dem and -side financing projects are now being implemented in many developing countries , yet evidence showing that they reach the poor is scanty . Methods A maternal health voucher scheme provided voucher-paid services in Jhang , a predominantly rural district of Pakistan , during 2010 . A pre-test/post-test quasi-experimental design was used to assess the changes in the proportion of facility-based deliveries and related maternal health services among the poor . Household interviews were conducted with r and omly selected women in the intervention and control union councils , before and after the intervention . A strong outreach model was used . Voucher promoters were given basic training in identification of poor women using the Poverty Scorecard for Pakistan , in the types of problems women could face during delivery , and in the promotion of antenatal care ( ANC ) , institutional delivery and postnatal care ( PNC ) . Voucher booklets valued at Rs . 4,000 ( $ 48 ) , including three ANC visits , a PNC visit , an institutional delivery , and a postnatal family planning visit , were sold for Rs . 100 ( $ 1.2 ) to low-income women targeted by project outreach workers . Women suffering from complications were referred to emergency obstetric care services . Analysis was conducted at the bivariate and the multivariate levels . At the multivariate level , logistic regression analysis was conducted to determine whether the increase in institutional delivery was greater among poor women ( defined for this study as women in the fourth or fifth quintiles ) relative to non-poor women ( defined for this study as women in the first quintile ) in the intervention union councils compared to the control union councils . Results Bivariate analysis showed significant increases in the institutional delivery rate among women in the fourth or fifth wealth quintiles in the intervention union councils but no significant changes in this indicator among women in the same wealth quintiles in the control union councils . Multivariate analysis showed that the increase in institutional delivery among poor women relative to non-poor women was significantly greater in the intervention compared to the control union councils . Conclusions Dem and -side financing projects using vouchers can be an effective way of reducing inequities in institutional delivery", "To report on the design and basic outcomes of three interventions aim ed at improving the use and quality of maternity care in rural China : financial interventions , training in clinical skills , and training in health education . Community-based cluster r and omized trials were carried out in one central and two western provinces between 2007 and 2009 : ( 1 ) financial interventions covered part of women ’s costs for prenatal and postnatal care , ( 2 ) training of midwives in clinical skills was given by local maternity care experts in two- or three-group training courses , ( 3 ) health education training for midwives and village doctors were given by local experts in health education in two- or three-group training courses . A survey was conducted in a stratified r and om sample of women who had been pregnant in the study period . 73 % of women ( n = 3,673 ) were interviewed within 1–10 months of giving birth . Outcomes were compared by the different intervention and control groups . Adjusted odds ratios were calculated by logistic regression to adjust for varying maternal characteristics . Most of the differences found between the groups were small and some varied between provinces . The financial intervention did not influence the number of visits , but was associated with increased caesarean sections and a decrease in many ultrasound tests . The clinical intervention influenced some indicators of care content . There was no consistent finding for the health education intervention . Financial and training interventions have the potential to improve maternity care , but better implementation is required . Unintended consequences , including overuse of technology , are possible", "There is promising recent evidence that poverty-targeted social cash transfers have potential to improve maternal health outcomes ; however , questions remain surrounding design features responsible for impacts . In addition , virtually no evidence exists from the African region . This study explores the impact of Zambia 's Child Grant Program on a range of maternal health utilization outcomes using a r and omized design and difference-in-differences multivariate regression from data collected over 24 months from 2010 to 2012 . Results indicate that while there are no measurable program impacts among the main sample , there are heterogeneous impacts on skilled attendance at birth among a sample of women residing in households having better access to maternal health services . The latter result is particularly interesting because of the overall low level of health care availability in program areas suggesting that dedicated program design or matching supply-side interventions may be necessary to leverage unconditional cash transfers in similar setting s to impact maternal health", "Although available evidence indicates that vouchers improve service utilization among the target population s , we do not know whether increased utilization results from improved access ( new clients who would not have used services without the voucher ) or from shifting clients from non-accredited to contracted service providers . This paper examines whether the safe motherhood voucher program in Kenya is associated with improved access to health facility delivery using information on births within two years preceding the survey in voucher and comparison sites . Data were collected in 2010 - 2011 and in 2012 among 2933 and 3094 women aged 15 - 49 years reporting 962 and 1494 births within two years before the respective surveys . Analysis entails cross-tabulations and estimation of multilevel r and om-intercept logit models . The results show that the proportion of births occurring at home declined by more than 10 percentage points while the proportion of births delivered in health facilities increased by a similar margin over time in voucher sites . The increase in facility-based births occurred in both public and private health facilities . There was also a significant increase in the likelihood of facility-based delivery ( odds ratios [ OR ] : 2.04 ; 95 % confidence interval [ CI ] : 1.40 - 2.98 in the 2006 voucher arm ; OR : 1.72 ; 95 % CI : 1.22 - 2.43 in the 2010 - 2011 voucher arm ) in voucher sites over time . In contrast , there were no significant changes in the likelihood of facility-based delivery in the comparison arm over time . These findings suggest that the voucher program contributed to improved access to institutional delivery by shifting births from home to health facilities . However , available evidence from qualitative data shows that some women who purchased the vouchers did not use them because of high transportation costs to accredited facilities . The implication is that substantial improvements in service uptake could be achieved if the program subsidized transportation costs as well", "BACKGROUND Scaling-up of effective preventive interventions in child and maternal health is constrained in many developing countries by lack of dem and . In Latin America , some governments have been trying to increase dem and for health interventions by making direct payments to poor households contingent on them keeping up-to- date with preventive health services . We undertook a public health programme effectiveness trial in Honduras to assess this approach , contrasting it with a direct transfer of re sources to local health teams . METHODS 70 municipalities were selected because they had the country 's highest prevalence of malnutrition . They were allocated at r and om to four groups : money to households ; re sources to local health teams combined with a community-based nutrition intervention ; both packages ; and neither . Evaluation surveys of about 5600 households were undertaken at baseline and roughly 2 years later . Pregnant women and mothers of children younger than 3 years old were asked about use of health services ( primary outcome ) and coverage of interventions such as immunisation and growth monitoring ( secondary outcome ) . Reports were supplemented with data from children 's health cards and government service utilisation data . Analysis was by mixed effects regression , accounting for the municipality-level r and omisation . FINDINGS The household-level intervention had a large impact ( 15 - 20 percentage points ; p coverage of antenatal care and well-child check-ups . Childhood immunisation series could thus be started more opportunely , and the coverage of growth monitoring was markedly increased ( 15 - 21 percentage points ; p Measles and tetanus toxoid immunisation were not affected . The transfer of re sources to local health teams could not be implemented properly because of legal complications . INTERPRETATION Conditional payments to households increase the use and coverage of preventive health care interventions", "BACKGROUND Caesarean section rates are increasing in Mexico and Latin America . This study evaluates the impact of a large-scale , conditional cash transfer programme in Mexico on caesarean section rates . The programme provides cash transfers to participating low income , rural households in Mexico conditional on accepting health care and nutrition supplements . METHODS The primary analyses uses retrospective reports from 979 women in poor rural communities participating in an effectiveness study and r and omly assigned to incorporation into the programme in 1998 or 1999 across seven Mexican states . Using multivariate and instrumental variable analyses , we estimate the impact of the programme on caesarean sections and predict the adjusted mean rates by clinical setting . Programme participation is measured by beneficiary status , programme months and cash transfers . RESULTS More than two-thirds of poor rural women delivered in a health facility . Beneficiary status is associated with a 5.1 percentage point increase in caesarean rates ; this impact increases to 7.5 percentage points for beneficiaries enrolled in the programme for > or=6 months before delivery . Beneficiaries had significantly higher caesarean delivery rates in social security facilities ( 24.0 compared with 5.6 % among non-beneficiaries ) and in other government facilities ( 19.3 compared with 9.5 % ) . CONCLUSION The Oportunidades conditional cash transfer programme is associated with higher caesarean section rates in social security and government health facilities . This effect appears to be driven by the increases in disposable income from the cash transfer . These findings are relevant to other countries implementing conditional cash transfer programmes and health care requirements", "Substantial healthcare expenses can impoverish households or push them further into poverty . In this paper , we examine the cost of obstetric care and the social and economic consequences associated with exposure to economic shocks up to a year following the end of pregnancy in Burkina Faso . Burkina Faso is a low-income country with poor health outcomes and a poorly functioning health system . We present an inter-disciplinary analysis of an ethnographic study of 82 women nested in a prospect i ve cohort study of 1013 women . We compare the experiences of women who survived life-threatening obstetric complications ( ' near-miss ' events ) with women who delivered without complications in hospitals . The cost of emergency obstetric care was significantly higher than the cost of care for uncomplicated delivery . Compared with women who had uncomplicated deliveries , women who survived near-miss events experienced substantial difficulties meeting the costs of care , reflecting the high cost of emergency obstetric care and the low socioeconomic status of their households . They reported more frequent sale of assets , borrowing and slower repayment of debt in the year following the expenditure . Healthcare costs consumed a large part of households ' re sources and women who survived near-miss events continued to spend significantly more on healthcare in the year following the event , while at the same time experiencing continued cost barriers to accessing healthcare . In-depth interviews confirm that the economic burden of emergency obstetric care contributed to severe and long-lasting consequences for women and their households . The necessity of meeting unexpectedly high costs challenged social expectations and patterns of reciprocity between husb and s , wives and wider social networks , placed enormous strain on everyday survival and shaped physical , social and economic well-being in the year that followed the event . In conclusion , we consider the implication s of our findings for financing mechanisms for maternity care in low-income setting" ]	4118450a-06ff-11f0-808a-c43d1ab1c353
Aims /hypothesisInsulin resistance , which manifests itself as endogenous glucose overproduction and reduced insulin-mediated glucose uptake , is a core defect in type 2 diabetes . Metformin and the peroxisome proliferator-activated receptor-γ agonists , the thiazolidinediones ( TZDs ) , both lower glucose , although their mechanism of action is still subject to debate . This review analyses the evidence relevant to these mechanisms in vivo . Material s and methods A systematic search of MEDLINE identified a total of 42 clinical studies that investigated the effects of TZDs ( n=23 ) and /or metformin ( n=19 ) on endogenous glucose production ( using tracer glucose techniques ) and peripheral glucose disposal ( using the euglycaemic – hyperinsulinaemic clamp ) in patients with type 2 diabetes ( n=549 ) . The original variables assessed were converted into st and ardised units and their mean group values were listed separately for open and placebo-controlled studies . Statistical analysis was scarried out , treating mean group values as individual values and comparing results ( both as absolute values and percentage changes from baseline ) across study categories ( open vs placebo-controlled , TZDs vs metformin ) . Results Both TZDs and metformin enhance insulin suppression of endogenous glucose production and fasting plasma glucose clearance . TZDs , but not metformin , also improve insulin-mediated glucose uptake at all insulin levels . Conclusions /interpretationIn patients with type 2 diabetes , metformin improves fasting hepatic insulin sensitivity and glucose clearance ; TZDs improve fasting hepatic insulin sensitivity and glucose clearance , and potentiate glucose disposal under insulinised conditions	[ "OBJECTIVE Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes . We therefore treated young , glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity , glucose metabolism , and glycogen synthase activity . RESEARCH DESIGN AND METHODS Relatives were r and omized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo . Before and after treatment , an oral glucose tolerance test ( OGTT ) and a euglycemic-hyperinsulinemic clamp ( 40 mU. m(-2 ) . min(-1 ) ) were performed , including 3-(3)H glucose infusion , glycolytic flux calculations , indirect calorimetry , and muscle biopsies . RESULTS Twelve relatives received troglitazone and 12 placebo ( aged 30.8 + /- 2.0 vs. 30.3 + /- 1.6 years , BMI 29.6 + /- 0.8 vs. 30.5 + /- 1.3 kg/m(2 ) ; means + /- SE ) . Area under the curve ( AUC ) for plasma glucose at the second OGTT was unchanged after troglitazone . In contrast , troglitazone reduced fasting ( from 70.3 + /- 6.9 to 52.2 + /- 5.8 vs. 73.6 + /- 11.0 to 73.3 + /- 6.5 pmol/l , P AUC plasma insulin ( mean [ CI ] from 335.7 [ 230.9 - 488.1 ] to 277.4 [ 179.4 - 428.8 ] vs. 313.8 [ 218.2 - 451.2 ] to 353.9 [ 208.3 - 601.3 ] pmol/l , P fasting plasma triglycerides were reduced by troglitazone ( from 1.86 + /- 0.33 to 1.38 + /- 0.27 vs. 2.22 + /- 0.44 to 2.35 + /- 0.46 mmol/l , P Insulin-stimulated glucose disposal increased in the troglitazone group ( from 208.3 + /- 23.7 to 263.5 + /- 30.4 vs. 197.1 + /- 20.0 to 200.8 + /- 20.8 mg . m(-2 ) . min(-1 ) , P glucose storage ( from 99.9 + /- 17.9 to 146.0 + /- 25.3 vs. 87.1 + /- 16.7 to 87.9 + /- 15.7 mg . m(-2 ) . min(-1 ) , P glucose-tolerant first-degree relatives , treatment with troglitazone improved insulin sensitivity almost 50 % , primarily due to increased glucose storage . It is suggested that the use of insulin action enhancers can be especially valuable in this group of subjects with a known high risk for developing type 2 diabetes", "Rosiglitazone , a thiazolidinedione , enhances peripheral insulin sensitivity in patients with type 2 diabetes . Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance , the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes . Therefore , 45 patients with newly diagnosed or diet-treated type 2 diabetes were r and omized for treatment with rosiglitazone ( 4 mg b.i.d . ) , metformin ( 1 g b.i.d . ) , or placebo in a 26-week double-blind trial . Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography ( PET ) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period . Rosiglitazone ( P metformin ( P mean glycosylated hemoglobin . The skeletal muscle glucose uptake was increased by 38 % ( P whole-body glucose uptake by 44 % in the rosiglitazone group . Furthermore , the exercise-induced increment during insulin stimulation was enhanced by 99 % ( P skeletal muscle or whole-body insulin sensitivity in the metformin group . In conclusion , rosiglitazone but not metformin 1 ) improves insulin responsiveness in resting skeletal muscle and 2 ) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes . Our results suggest that rosiglitazone improves synergic action of insulin and exercise", "OBJECTIVE To examine the effect of rosiglitazone on insulin resistance and blood pressure in patients with essential hypertension , classified based on abnormalities of their renin-angiotensin system . RESEARCH DESIGN AND METHODS A total of 24 hypertensive nondiabetic patients ( age 58 + /- 6 years , BMI 30 + /- 5 kg/m2 ) were studied before and after rosiglitazone treatment . After 2 weeks off antihypertensive medication , subjects received a euglycemic-hyperinsulinemic clamp ( 40 mU. m(-2 ) . min(-1 ) ) with 6,6-[2H2]glucose infusion , ambulatory blood pressure monitoring , and blood tests for cardiovascular risk factors . Subjects were then placed on rosiglitazone ( 4 mg orally b.i.d . ) and their usual antihypertensive medications ( but not ACE inhibitors ) for 16 weeks , and baseline tests were repeated . RESULTS There was no change in fasting plasma glucose ( 83 + /- 2 vs. 82 + /- 2 mg/dl , P = 0.60 ) , but fasting insulin decreased ( 16.1 + /- 1.4 vs. 12.5 + /- 0.9 micro U/ml , P Total glucose disposal during the clamp increased ( 5.0 + /- 0.4 vs. 5.9 + /- 0.5 mg . kg(-1 ) . min(-1 ) , P hepatic glucose output . There were significant decreases in mean 24-h systolic ( 138 + /- 2 vs. 134 + /- 2 mmHg , P diastolic ( 85 + /- 2 vs. 80 + /- 2 mmHg , P blood pressure , and the decline in systolic blood pressure was correlated with the improvement in insulin sensitivity ( r = 0.59 , P Triglycerides ( 135 + /- 16 vs. 89 + /- 8 mg/dl , P LDL cholesterol ( 129 + /- 6 vs. 122 + /- 8 mg/dl , P = 0.18 ) , and HDL cholesterol ( 51 + /- 3 vs. 46 + /- 3 mg/dl , P LDL-to-HDL ratio . Plasminogen activator inhibitor-1 and C-reactive protein also declined significantly . CONCLUSIONS Rosiglitazone treatment of nondiabetic hypertensive patients improves insulin sensitivity , reduces systolic and diastolic blood pressure , and induces favorable changes in markers of cardiovascular risk . Insulin sensitizers may provide cardiovascular benefits when used in the treatment of patients with hypertension", "Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels . We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type 2 diabetic patients . To avoid the confounding effect of improved glycemic control on insulin action and secretion , patients were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion ( CSII ) before r and omization to CSII plus troglitazone ( n = 10 ) or CSII plus metformin ( n = 10 ) ; euglycemia was maintained for another 6 - 7 weeks . Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1 ) at baseline , 2 ) after 4 weeks of CSII , and 3 ) after CSII plus either troglitazone or metformin . The 24-h glucose , insulin , and C-peptide profiles were performed on the day before the second and third glucose clamps . Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent ( mean 24-h glucose : troglitazone , 6.2+/-0.6 mmol/l ; metformin , 6.2 + /-0.3 mmol/l ) . Insulin requirements decreased 53 % with troglitazone compared with CSII alone ( 48+/-4 vs. 102+/-13 U/day , P metformin ( 76+/-13 vs. 110+/-18 U/day , P 24-h C-peptide profiles were similar . Normal fasting hepatic glucose output was maintained with both agents despite lower insulin levels than on CSII alone . Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin , but improved 29 % with CSII plus troglitazone ( P metformin patients ( P metformin has no effect on insulin-stimulated glucose disposal independent of glycemic control in type 2 diabetes . Troglitazone ( 600 mg/day ) has greater insulin-sparing effects than metformin ( 1,700 mg/day ) in CSII-treated euglycemic patients . This is probably explained by the peripheral tissue insulin-sensitizing effects of troglitazone", "UNLABELLED Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study . Metformin 0.5 g trice daily or placebo were given for 4 weeks . At the end of each period fasting and day-time postpr and ial values of plasma glucose , insulin , C-peptide and lactate were determined , and in vivo insulin action was assessed using the euglycemic clamp in combination with [3 - 3H]glucose tracer technique . Metformin treatment significantly reduced mean day-time plasma glucose levels ( 10.2 + /- 1.2 vs 11.4 + /- 1.2 mmol/l , P less than 0.01 ) without enhancing mean day-time plasma insulin ( 43 + /- 4 vs 50 + /- 7 mU/l , NS ) or C-peptide levels ( 1.26 + /- 0.12 vs 1.38 + /- 0.18 nmol/l , NS ) . Fasting plasma lactate was unchanged ( 1.57 + /- 0.16 vs 1.44 + /- 0.11 mmol/l , NS ) , whereas mean day-time plasma lactate concentrations were slightly increased ( 1.78 + /- 0.11 vs 1.38 + /- 0.11 mmol/l , P less than 0.01 ) . The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization ( 370 + /- 38 vs 313 + /- 33 mg.m-2.min-1 , P less than 0.01 ) , whereas insulin-mediated suppression of hepatic glucose production was unchanged . Also basal glucose clearance was improved ( 61.0 + /- 5.8 vs 50.6 + /- 2.8 ml.m-2.min-1 , P less than 0.05 ) , whereas basal hepatic glucose production was unchanged ( 81 + /- 6 vs 77 + /- 4 mg.m-2.min-1 , NS ) . CONCLUSIONS 1 ) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion . ( ABSTRACT TRUNCATED AT 250 WORDS", "The effect of metformin or rosiglitazone monotherapy versus placebo on insulin signaling and gene expression in skeletal muscle of patients with newly diagnosed type 2 diabetes was determined . A euglycemic-hyperinsulinemic clamp , combined with skeletal muscle biopsies and glucose uptake measurements over rested and exercised muscle , was performed before and after 26 weeks of metformin ( n = 9 ) , rosiglitazone ( n = 10 ) , or placebo ( n = 11 ) treatment . Insulin-mediated whole-body and leg muscle glucose uptake was enhanced 36 and 32 % , respectively , after rosiglitazone ( P metformin or placebo treatment . Insulin increased insulin receptor substrate 1 ( IRS-1 ) tyrosine phosphorylation , IRS-1-associated phosphatidylinositol ( PI ) 3-kinase activity , and phosphorylation of Akt Ser473 and AS160 , a newly described Akt substrate that plays a role in GLUT4 exocytosis , approximately 2.3 fold before treatment . These insulin signaling parameters were unaltered after metformin , rosiglitazone , or placebo treatment . Expression of selected genes involved in glucose and fatty acid metabolism in skeletal muscle was unchanged between the treatment groups . Low-intensity acute exercise increased insulin-mediated glucose uptake but was without effect on insulin signaling . In conclusion , the insulin-sensitizing effects of rosiglitazone are independent of enhanced signaling of IRS-1/PI 3-kinase/Akt/AS160 in patients with newly diagnosed type 2 diabetes", "Pioglitazone increases the insulin sensitivity of peripheral tissues and may provide an alternative first-line treatment for type 2 diabetes . This study compared metabolic control in drug-naive type 2 diabetes patients given either pioglitazone or metformin . Eleven hundred and ninety-nine patients with poorly controlled type 2 diabetes mellitus [ glycosylated hemoglobin ( HbA1c ) , 7.5 - 11 % ; normal , 4.3 - 6.1 % ] were r and omized to receive either pioglitazone ( or metformin ( HbA1c , fasting plasma glucose ( FPG ) , insulin levels , total cholesterol ( TC ) , high density lipoprotein cholesterol ( HDL-C ) , low density lipoprotein cholesterol , triglycerides , free fatty acids , and urinary albumin/creatinine ratio were measured . Mean HbA1c decreased in both treatment groups from baseline to wk 52 ( -1.4 % and -1.5 % ) . Significantly greater mean reductions in FPG were observed in the pioglitazone group ( -45.0 mg/dl ; -2.5 mmol/liter ) than in the metformin ( -39.6 mg/dl ; -2.2 mmol/liter ) group ( P = 0.016 ) . Favorable changes in triglycerides and HDL-C were more pronounced with pioglitazone . Although low density lipoprotein cholesterol and TC levels increased with pioglitazone , TC/HDL-C ratios decreased similarly with both treatments . The urinary albumin/creatinine ratio was reduced by 19 % with pioglitazone treatment , but remained unchanged with metformin therapy ( -1 % ; P = 0.002 ) . There was an increase in body weight of 1.9 kg in the pioglitazone group and a decrease of 2.5 kg in the metformin group . The overall frequency of adverse events was similar between treatment groups , but adverse event profiles were different between treatment groups . HbA1c reduction is similar after pioglitazone and metformin monotherapies , but differences in FPG , plasma lipids , and adverse effects between the two compounds may influence decision-making in individual prescribers", "We investigated whether the effect of troglitazone on glucose disposal is associated with altered insulin signaling . Nondiabetic first-degree relatives of type 2 diabetic patients ( age 30 + /- 2 years , BMI 30 + /- 1 kg/m(2 ) ; n = 20 ) were r and omized in a double-blind manner to 3 months of troglitazone ( 200 mg/day ) or placebo treatment . Before and after treatment , 3-h euglycemic-hyperinsulinemic glucose clamps ( 40 mU. m(-2 ) . min(-1 ) ) were performed , and muscle biopsies were obtained immediately before and after the clamps . In the biopsies , insulin receptor kinase ( IRK ) activity , insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase ( PI3 K ) activity , Ser(473 ) and Thr(308 ) phosphorylation of protein kinase B ( PKB ) , and protein expression of IRS-1 , IRS-2 , phosphoinositol-dependent kinase-1 ( PDK-1 ) , PKB , and GLUT-4 were determined . After troglitazone treatment , insulin-stimulated glucose disposal was increased compared with pretreatment and placebo ( 279 + /- 37 vs. 211 + /- 26 and 200 + /- 25 mg . m(-2 ) . min(-1 ) ; both P IRK and PI3 K activities were not altered by troglitazone , but PKB Ser(473 ) phosphorylation was enhanced compared with pretreatment and placebo at the clamp insulin level ( 138 + /- 36 vs. 77 + /- 16 and 55 + /- 13 internal st and ard units ; both P PKB Thr(308 ) phosphorylation also tended to be higher , but this was not statistically significant . Troglitazone did not alter insulin receptor number or IRS-1 , IRS-2 , PKB , PDK-1 , or GLUT-4 protein expression . We conclude that increased PKB phosphorylation may contribute to the insulin-sensitizing effects of thiazolidinediones in human skeletal muscle", "To establish the antihyperglycemic mechanisms of metformin in non-insulin-dependent diabetes mellitus ( NIDDM ) independently of the long-term , aspecific effects of removal of glucotoxicity , 21 NIDDM subjects ( 14 obese , 7 nonobese ) were studied on two separate occasions , with an isoglycemic ( plasma glucose ∼9 mM ) hyperinsulinemic ( two-step insulin infusion , 2 h each , at the rate of 4 and 40 mU · m−2 · min−1 ) clamp combined with [3−3H]glucose infusion and indirect calorimetry , after administration of either metformin ( 500 mg per os , at –5 and –1 h before the clamp ) or placebo . Compared with placebo , hepatic glucose production ( HGP ) decreased ∼30 % more after metformin ( from 469 ± 50 to 330 ± 54 μmol/min ) , but glucose uptake did not increase . Metformin suppressed free fatty acids ( FFAs ) by ∼17 % ( from 0.42 ± 0.04 to 0.35 ± 0.04 mM ) and lipid oxidation by ∼25 % ( from 4.5 ± 0.4 to 3.4 ± 0.4 μmol · kg−1 · min−1 ) and increased glucose oxidation by ∼ 16 % ( from 16.2 ± 1.4 to 19.3 ± 1.3 μmol.kg−1 · min−1 ) compared with placebo ( P affect nonoxidative glucose metabolism , protein oxidation , or total energy expenditure . Suppression of FFA and lipid oxidation after metformin correlated with suppression of HGP ( r = 0.70 and r = 0.51 , P of metformin in obese and nonobese subjects were no different . We conclude that the specific , antihyperglycemic effects of metformin in the clinical condition of hyperglycemia in NIDDM are primarily due to suppression of HGP , not stimulation of glucose uptake , and are mediated , at least in part , by suppression of FFA and lipid oxidation", "The effect of metformin therapy on glucose metabolism was examined in eight overweight newly presenting untreated type II diabetic patients ( five males , three females ) . Patients were treated for 12 weeks with either metformin ( 850 mg x 3 ) or matching placebo using a double-blind crossover study design ; patients were studied at presentation and at the end of each treatment period . Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase ( GS ) before and during a 4-hour hyperinsulinemic euglycemic clamp ( 100 mU.kg-1 x h-1 ) . Metformin therapy was associated with a significant decrease in fasting blood glucose ( 6.8 + /- 0.6 v 8.3 + /- 0.9 mmol . L-1 , P glycosylated hemoglobin ( [ HbA1 ] 7.7 % + /- 0.4 % v 8.5 % + /- 0.5 % , P Fasting hepatic glucose production ( HGP ) was also significantly decreased following metformin therapy ( 1.98 + /- 0.13 v 2.41 + /- 0.20 mg.kg-1 x min-1 , P fasting insulin and C-peptide concentrations remained unaltered . The decrease in basal HGP correlated closely with the decrease in fasting blood glucose concentration ( r = .92 , P Insulin-stimulated glucose uptake was assessed using the hyperinsulinemic euglycemic clamp technique and was increased post-metformin ( 3.8 + /- 0.6 v 3.1 + /- 0.7 mg.kg-1 x min-1 , P nonoxidative glucose metabolism ( 1.1 + /- 0.6 v 0.4 + /- 0.6 mg.kg-1 x min-1 , P oxidative glucose metabolism did not change . Metformin had no measurable effect on insulin activation of skeletal muscle GS , the rate-limiting enzyme controlling muscle glucose storage . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND Troglitazone decreases insulin resistance and hyperglycemia in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) , but its effects on subjects without diabetes are not known . METHODS We performed oral and intravenous glucose-tolerance tests , studies with the euglycemic-hyperinsulinemic clamp , meal-tolerance tests , and 24-hour blood-pressure measurements at base line and after the administration of troglitazone , 200 mg orally twice daily , or placebo for 12 weeks in 18 nondiabetic obese subjects , 9 of whom had impaired glucose tolerance . RESULTS The mean ( + /- SD ) rates of glucose disposal increased from 4.7 + /- 1.7 to 6.0 + /- 1.7 mg per kilogram of body weight per minute ( P = 0.004 ) and from 9.0 + /- 1.8 to 9.9 + /- 1.3 mg per kilogram per minute ( P = 0.02 ) during insulin infusions of 40 and 300 mU per square meter of body-surface area per minute , respectively , in the troglitazone group . The insulin-sensitivity index , calculated from the results of intravenous glucose-tolerance tests , increased from 0.7 + /- 0.6 x 10(-4 ) to 1.6 + /- 0.9 x 10(-4 ) in subjects given troglitazone , and their glycemic response to oral glucose and to mixed meals decreased . The mean fasting plasma insulin concentration decreased by 48 percent ( P = 0.002 ) , and the plasma insulin response to oral glucose and mixed meals decreased by 40 and 41 percent , respectively . The changes were similar in the subjects with normal glucose tolerance and those with impaired glucose tolerance . Systolic and diastolic blood pressure decreased by 5 + /- 2 mm Hg ( P = 0.05 ) and 4 + /- 2 mm Hg ( P = 0.04 ) , respectively , after treatment with troglitazone . There were virtually no changes in the placebo group . CONCLUSIONS Troglitazone decreases insulin resistance and improves glucose tolerance in obese subjects with either impaired or normal glucose tolerance . The ability of troglitazone to reduce insulin resistance could be useful in preventing NIDDM", "Pioglitazone , a thiazolidinedione , improves glycemic control primarily by increasing peripheral insulin sensitivity in patients with type 2 diabetes , whereas metformin , a biguanide , exerts its effect primarily by decreasing hepatic glucose output . In the first head-to-head , double-blind clinical trial comparing these two oral antihyperglycemic medications ( OAMs ) , we studied the effect of 32-wk monotherapy on glycemic control and insulin sensitivity in 205 patients with recently diagnosed type 2 diabetes who were naive to OAM therapy . Subjects were r and omized to either 30 mg pioglitazone or 850 mg metformin daily with titrations upward to 45 mg ( 77 % of pioglitazone patients ) and 2550 mg ( 73 % of metformin patients ) , as indicated , to achieve fasting plasma glucose levels of less than 7.0 mmol/liter ( 126 mg/dl ) . Pioglitazone was comparable to metformin in improving glycemic control as measured by hemoglobin A1C and fasting plasma glucose . At endpoint , pioglitazone was significantly more effective than metformin in improving indicators of insulin sensitivity , as determined by reduction of fasting serum insulin ( P = 0.003 ) and by analysis of homeostasis model assessment for insulin sensitivity ( HOMA-S ; P = 0.002 ) . Both OAM therapies were well tolerated . Therefore , pioglitazone and metformin are equally efficacious in regard to glycemic control , but they exert significantly different effects on insulin sensitivity due to differing mechanisms of action . The more pronounced improvement in indicators of insulin sensitivity by pioglitazone , as compared with metformin monotherapy in patients recently diagnosed with type 2 diabetes who are OAM-naive , may be of interest for further clinical evaluation", "The effects of metformin on glycaemia , insulin and c-peptide levels , hepatic glucose production and insulin sensitivity ( using the euglycaemic , hyperinsulinaemic clamp ) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol : Stage 1 - -no metformin for four weeks ; stage 2 - -metformin 500 mg mane ; stage 3 - -metformin 500 mg thrice daily ; stage 4 - -metformin 1000 mg thrice daily . Results are expressed as Mean + /- SEM . Fasting blood glucose decreased from basal values ( 9.7 + /- 1.0 mmol/L ) by 13 % at stage 2 , 34 % at stage 3 and 41 % at stage 4 ( p less than 0.02 vs basal for all stages ; p less than 0.02 stage 2 vs stage 3 ) . Post-pr and ial glycaemia was significantly improved only with metformin 3000mg/day ( p less than 0.05 ) . Fasting , meal-stimulated and total insulin and c-peptide levels showed no change . Hepatic glucose output did not change significantly with metformin . Insulin sensitivity , measured as total glucose utilisation during hyperinsulinaemia , increased from stage 1 ( 10.3 + /- 2.1 mumoL/kg/min ) by 23 % at stage 3 ( p less than 0.05 ) and by 29 % at stage 4 ( p less than 0.02 ) . Basal metabolic clearance of glucose increased compared to stage 1 ( 1.69 + /- 0.16 mL/kg/min ) by 30 % at stage 2 , 53 % at stage 3 and 44 % at stage 4 ( all p less than 0.02 ) . This study demonstrates that improved efficiency of glucose utilisation , both basally and under conditions of euglycaemic hyperinsulinaemia , is the basis of metformin 's antihyperglycaemic action", "Whereas thiazolidinediones ( TZDs ) are known to rapidly improve insulin action in animals , short duration s of TZD therapy have never been studied in humans . Among the many known actions of TZDs , increased circulating levels of the high molecular weight ( HMW ) multimer of adiponectin may be an important insulin-sensitizing mechanism . We examined the effects of only 21 days of 45 mg of pioglitazone ( P+ ) versus placebo ( P- ) in nine subjects with type 2 diabetes ( HbA(1c ) , 10.9 + /- 0.6 % ; BMI , 31.9 + /- 1.5 kg/m(2 ) ) . Total adiponectin levels increased by approximately twofold in P+ in association with increased adipose tissue gene expression . However , plasma free fatty acid and glucose levels were unchanged , and there were only minimal changes in other \" adipokines . \" Glucose fluxes ( [3-(3)H]glucose infusion ) were measured during 6-h euglycemic ( 5 mmol/l ) \" pancreatic clamp \" studies ( somatostatin/glucagon/growth hormone ) with stepped insulin levels . Pioglitazone induced marked decreases in endogenous glucose production ( P+ = 0.9 + /- 0.1 vs. P- = 1.7 + /- 0.3 mg . kg(-1 ) . min(-1 ) ; P ratio of HMW adiponectin/total levels ( r(2 ) = 0.90 ) . Maximal insulin stimulation ( approximately 400 microU/ml ) revealed pioglitazone-associated increases in glucose uptake ( P+ = 10.5 + /- 0.9 vs. P- = 8.9 + /- 0.8 mg . kg(-1 ) . min(-1 ) ; P HMW or total adiponectin levels . Thus , only 21 days of pioglitazone therapy improved insulin action in humans with type 2 diabetes . Increased abundance of the HMW adiponectin multimer may contribute to the hepatic insulin-sensitizing effects of these agents" ]	41184582-06ff-11f0-808a-c43d1ab1c353
Objectives The high prevalence of cardiovascular disease ( CVD ) and the increased cost of treatment have prompted strategies for the primary prevention of CVD in the UK to move towards the use of vali date d CVD risk scores to identify individuals at the highest risk . There are no review s evaluating the effectiveness of this strategy as a means of reducing CVD risk or mortality . This review summarizes current evidence for and against the use of vali date d CVD risk scores for the primary prevention of CVD . Design We utilized an in depth search strategy to search MEDLINE , EMBASE and the Cochrane data base of clinical trials , expert opinions were sought and reference lists of identified studies and relevant review s were checked . Due to a lack of homogeneity in outcomes and risk scores used it was not possible to conduct a meta- analysis of the identified studies . Setting The majority of included trials were carried out in a primary care setting . 2 trials were carried out in North America , 2 in Sc and inavia and 1 in the UK . Participants 31,651 participants in total were recruited predominantly from a primary care setting . Participants were aged 18 - 65 years old and were free from CVD at baseline . Main outcome measures Outcome measures used in the included studies were change in vali date d CVD risk score and CVD/All-cause mortality . Results We identified 16 papers which matched the inclusion criteria reporting 5 unique trials . Due to a lack of homogeneity in outcomes and risk scores used it was not possible to conduct a meta- analysis of the identified studies . Only one study reported a significant difference in risk score at follow up and one study reported a significant difference in total mortality , however significant differences in individual risk factors were reported by the majority of identified studies . Conclusions This review demonstrates the potential for multifactorial interventions aim ed at individuals selected by CVD risk scores for lowering CVD risk and mortality . However , the majority of studies in this area do not provide an intensity of intervention which is sufficient in significantly reducing CVD mortality or vali date d CVD risk	[ "BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD", "BACKGROUND The multiprofessional teams in Finnish health centres are well placed to carry out interventions aim ed at the prevention of cardiovascular diseases . AIM To evaluate the effectiveness of an individually tailored multifactorial lifestyle intervention in primary care for individuals at high risk for cardiovascular disease . DESIGN OF STUDY A r and omised controlled trial was conducted over 24 months with interim assessment s at six and 12 months . SETTING A health centre in Finl and with a patient population of 11,000 . METHOD One hundred and fifty adults aged 18 to 65 years old with existing cardiovascular disease or multiple risk factors were r and omised to active multiprofessional risk factor intervention or to st and ard care . The main outcome measure was a change in cardiovascular risk-factor score . Secondary outcomes were changes in blood pressure , weight , body-mass index , serum cholesterol , blood glucose , smoking cessation , and exercise habits . RESULTS The cardiovascular risk score decreased by 28 % in the intervention group ( 23 % in the control group ) , body weight decreased by 3.7 % ( 2 % ) and total cholesterol decreased by 10.8 % ( 6.5 % ) , while time engaged in exercise increased by 39 % ( 43 % ) . Differences were not significant . CONCLUSIONS Cardiovascular risk levels of high-risk individuals decreased in both intervention and control groups . Primary care prevention should be targeted to high-risk persons . Long-term follow-up studies are needed", "Objective To develop and vali date a new diabetes risk algorithm ( the QDScore ) for estimating 10 year risk of acquiring diagnosed type 2 diabetes over a 10 year time period in an ethnically and socioeconomically diverse population . Design Prospect i ve open cohort study using routinely collected data from 355 general practice s in Engl and and Wales to develop the score and from 176 separate practice s to vali date the score . Participants 2 540 753 patients aged 25 - 79 in the derivation cohort , who contributed 16 436 135 person years of observation and of whom 78 081 had an incident diagnosis of type 2 diabetes ; 1 232 832 patients ( 7 643 037 person years ) in the validation cohort , with 37 535 incident cases of type 2 diabetes . Outcome measures A Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort and to derive a risk equation in men and women . The predictive variables examined and included in the final model were self assigned ethnicity , age , sex , body mass index , smoking status , family history of diabetes , Townsend deprivation score , treated hypertension , cardiovascular disease , and current use of corticosteroids ; the outcome of interest was incident diabetes recorded in general practice records . Measures of calibration and discrimination were calculated in the validation cohort . Results A fourfold to fivefold variation in risk of type 2 diabetes existed between different ethnic groups . Compared with the white reference group , the adjusted hazard ratio was 4.07 ( 95 % confidence interval 3.24 to 5.11 ) for Bangladeshi women , 4.53 ( 3.67 to 5.59 ) for Bangladeshi men , 2.15 ( 1.84 to 2.52 ) for Pakistani women , and 2.54 ( 2.20 to 2.93 ) for Pakistani men . Pakistani and Bangladeshi men had significantly higher hazard ratios than Indian men . Black African men and Chinese women had an increased risk compared with the corresponding white reference group . In the validation data set , the model explained 51.53 % ( 95 % confidence interval 50.90 to 52.16 ) of the variation in women and 48.16 % ( 47.52 to 48.80 ) of that in men . The risk score showed good discrimination , with a D statistic of 2.11 ( 95 % confidence interval 2.08 to 2.14 ) in women and 1.97 ( 1.95 to 2.00 ) in men . The model was well calibrated . Conclusions The QDScore is the first risk prediction algorithm to estimate the 10 year risk of diabetes on the basis of a prospect i ve cohort study and including both social deprivation and ethnicity . The algorithm does not need laboratory tests and can be used in clinical setting s and also by the public through a simple web calculator ( www.qdscore.org )", "Objective To evaluate the impact of telling patients their estimated spirometric lung age as an incentive to quit smoking . Design R and omised controlled trial . Setting Five general practice s in Hertfordshire , Engl and . Participants 561 current smokers aged over 35 . Intervention All participants were offered spirometric assessment of lung function . Participants in intervention group received their results in terms of “ lung age ” ( the age of the average healthy individual who would perform similar to them on spirometry ) . Those in the control group received a raw figure for forced expiratory volume at one second ( FEV1 ) . Both groups were advised to quit and offered referral to local NHS smoking cessation services . Main outcome measures The primary outcome measure was verified cessation of smoking by salivary cotinine testing 12 months after recruitment . Secondary outcomes were reported changes in daily consumption of cigarettes and identification of new diagnoses of chronic obstructive lung disease . Results Follow-up was 89 % . Independently verified quit rates at 12 months in the intervention and control groups , respectively , were 13.6 % and 6.4 % ( difference 7.2 % , P=0.005 , 95 % confidence interval 2.2 % to 12.1 % ; number needed to treat 14 ) . People with worse spirometric lung age were no more likely to have quit than those with normal lung age in either group . Cost per successful quitter was estimated at £ 280 ( € 366 , $ 556 ) . A new diagnosis of obstructive lung disease was made in 17 % in the intervention group and 14 % in the control group ; a total of 16 % ( 89/561 ) of participants . Conclusion Telling smokers their lung age significantly improves the likelihood of them quitting smoking , but the mechanism by which this intervention achieves its effect is unclear . Trial registration National Research Register N0096173751", "Background : In this study , we tested the efficacy of a low-intensity lifestyle intervention aim ed at reducing the risk of cardiovascular disease among mid-life individuals . Methods : We conducted a r and omized controlled trial in which participants were r and omly assigned either to receive a health report card with counselling ( from a Telehealth nurse ) on smoking , exercise , nutrition and stress or to receive usual care . The patients were divided into 2 groups on the basis of risk : the primary prevention group , with a Framingham risk score of 10 % or higher ( intervention , n = 157 ; control , n = 158 ) , and the secondary prevention group , who had a diagnosis of coronary artery disease ( intervention , n = 153 ; control , n = 143 ) . The primary outcome was a change in the Framingham global risk score between baseline and 1-year follow-up . Data were analyzed separately for the 2 prevention groups using an intention-to-treat analysis controlling for covariates . Results : Within the primary prevention group , there were statistically significant changes for the treatment group relative to the controls , from baseline to year 1 , in Framingham score ( intervention , –3.10 [ 95 % confidence interval ( CI ) –3.98 to –2.22 ] ; control , –1.30 [ 95 % CI –2.18 to –0.42 ] ; p 0.01 ) and scores for total cholesterol ( intervention , –0.41 [ 95 % CI –0.59 to –0.23 ] ; control , –0.14 [ 95 % CI –0.32 to 0.04 ] ; p ( intervention , –7.49 [ 95 % CI –9.97 to –5.01 ] ; control , –3.58 [ 95 % CI –6.08 to –1.08 ] ; p level ( intervention , 0.30 [ 95 % CI 0.13 to 0.47 ] ; control , –0.05 [ 95 % CI –0.22 to 0.12 ] ; p confidence ( intervention , 0.20 [ 95 % CI 0.09 to 0.31 ] ; control , 0.04 [ 95 % CI –0.07 to 0.15 ] ; p intervention addressing multiple risk factors for primary prevention at 1 year using Framingham risk score report cards and telephone counselling . ( Requirement for clinical trial registration waived [ enrolment completed before requirement became applicable ] .", "The Multiple Risk Factor Intervention Trial was a r and omized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease ( CHD ) in 12,866 high-risk men aged 35 to 57 years . Men were r and omly assigned either to a special intervention ( SI ) program consisting of stepped-care treatment for hypertension , counseling for cigarette smoking , and dietary advice for lowering blood cholesterol levels , or to their usual sources of health care in the community ( UC ) . Over an average follow-up period of seven years , risk factor levels declined in both groups , but to a greater degree for the SI men . Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group , a statistically nonsignificant difference of 7.1 % ( 90 % confidence interval , -15 % to 25 ) . Total mortality rates were 41.2 per 1,000 ( SI ) and 40.4 per 1,000 ( UC ) . Three possible explanations for these findings are considered : ( 1 ) the overall intervention program , under these circumstances , does not affect CHD mortality ; ( 2 ) the intervention used does affect CHD mortality , but the benefit was not observed in this trial of seven years ' average duration , with lower-than-expected mortality and with considerable risk factor change in the UC group ; and ( 3 ) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort , with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects . This last possibility was considered most likely , needs further investigation , and lends support to some preventive measures while requiring re assessment of others" ]	41184604-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Consideration of the biologic width in restorative dentistry seems to be important for maintaining periodontal health . OBJECTIVE To evaluate the dimensions of the biologic width in humans . MATERIAL S AND METHODS A systematic literature search was performed for publications published by 28 September 2012 using five different electronic data bases ; this search was complemented by a manual search . Two review ers conducted the study selection , data collection , and validity assessment . The PRISMA criteria were applied . From 615 titles identified by the search strategy , 14 publications were included and six were suitable for meta-analyses . RESULTS Included studies were published from the years 1924 to 2012 . They differed with regard to measurements of the biologic width . Mean values of the biologic width obtained from two meta-analyses ranged from 2.15 to 2.30 mm , but large intra- and inter-individual variances ( subject sample range : 0.2 - 6.73 mm ) were observed . The tooth type and site , the presence of a restoration and periodontal diseases/surgery affected the dimensions of the biologic width . Pronounced heterogeneity among studies regarding methods and outcome measures exists . CONCLUSIONS No universal dimension of the biologic width appears to exist . Establishment of periodontal health is suggested prior to the assessment of the biologic width within reconstructive dentistry	[ "BACKGROUND Despite the broad use of crown-lengthening surgery ( CLS ) , there is no complete agreement as to the desired amount of exposed sound tooth structure needed to accommo date both the restorative needs and the reformation of the supraosseous gingiva ( SOG ) . Classically , it has been proposed that approximately 3 mm of SOG , the amount considered by most to be present before surgery , will be reformed after CLS . The purpose of this study was to test the viability of transsulcular probing ( TSP ) and to determine whether the SOG that forms after CLS is the same as that measured preoperatively . METHODS Nineteen patients underwent CLS with the surgical tooth acting both as the control and the test site . The SOG dimension was measured by TSP before and 6 months after surgery . Stents were used as fixed reference points . Intraclass correlations were calculated to test for the reliability of TSP measurements versus direct-bone-level ( DBL ) measurements . A Wilcoxon signed-rank test was used to compare the means for the mean buccal , mean lingual , and overall mean SOG dimensions at baseline to corresponding measurements at 6 months . RESULTS Intraclass correlation coefficients for TSP measures of SOG to DBL measures of SOG ranged from 83.4 % agreement to 91.9 % agreement , with all correlations being highly significant ( P agreement between TSP and DBL . The differences in SOG dimensions , 6 months after surgery compared to baseline , were as follows : mean buccal , 0.51 mm ; mean lingual/palatal , 0.61 mm ; overall mean , 0.56 mm . These differences were significant for all three comparisons ( P TSP is an accurate alternative method to DBL in clinical ly determining SOG dimensions . Six months after CLS , the SOG dimension was reduced by 0.51 to 0.61 mm compared to the presurgical measurement , with these mean differences being statistically significant", "STATEMENT OF PROBLEM The clinical impact of posterior crown margin placement on gingival health has not been thoroughly quantified . PURPOSE This study evaluated the effect of posterior crown margin placement with multivariate analysis . MATERIAL AND METHODS Ten general dentists review ed 240 patients with 480 metal-ceramic crowns in a prospect i ve clinical trial . The alloy was r and omly selected from 2 high gold , 1 low gold , and 1 palladium alloy . Variables were the alloy used , oral hygiene index score before treatment , location of crown margins at baseline , and plaque index and sulcus bleeding index scores recorded for restored and control teeth after 1 year . The effect of crown margin placement on sulcular bleeding and plaque accumulation was analyzed with regression models ( P probability of plaque at 1 year increased with increasing oral hygiene index score before treatment . The lingual surfaces demonstrated the highest probability of plaque . The risk of bleeding at intrasulcular posterior crown margins was approximately twice that at supragingival margins . Poor oral hygiene before treatment and plaque also were associated with sulcular bleeding . Facial sites exhibited a lower probability of sulcular bleeding than lingual surfaces . Type of alloy did not influence sulcular bleeding . CONCLUSION In this study , placement of crown margins was one of several parameters that affected gingival health", "BACKGROUND Previous surgical crown lengthening studies have investigated positional changes of the free gingival margin but not the biological width . Histological studies utilizing animal models have shown that postoperative crestal resorption allowed reestablishment of the biological width . However , very little work has been done in humans . Therefore , the purpose of this study was to evaluate the positional changes of the periodontal tissues , particularly the biological width , following surgical crown lengthening in human subjects . METHODS Twenty-three ( 23 ) patients who needed surgical crown lengthening to gain retention necessary for prosthetic treatment and /or to access caries , tooth fracture , or previous prosthetic margins entered the study . The following parameters were obtained from line angles of treated teeth ( teeth requiring surgical crown lengthening ) and adjacent teeth with adjacent and non-adjacent sites : plaque and gingival indexes , free gingival margin , probing depth , attachment level , bone level , direct bone level , and biological width . During surgery , the bone level was reduced based on the future prosthetic margin and predetermined biological width ; flaps were placed at the bony crest . Patients were examined at baseline and at 3 and 6 months postoperatively . RESULTS Eighteen patients completed the study . Overall , the amount of bone resected was 1 to 5 mm . At 90 % of treated sites , > or = 3 mm of bone was removed . At 3 months , the apical displacement of the free gingival margin at non-adjacent , adjacent , and treated sites was 2.46 + /- 0.25 mm , 2.68 + /- 0.20 mm , and 3.07 + /- 0.16 mm , respectively . There was no significant change in the position of the free gingival margin from 3 to 6 months . The biological width at all sites was smaller at 3 and 6 months compared to baseline ( P surgical crown lengthening , the bone level was lowered for placement of the prosthetic margin and reestablishment of the biological width . The biological width , at treated sites , was reestablished to its original vertical dimension by 6 months . In addition , a consistent 3 mm gain of coronal tooth structure was observed at the 3- and 6-month examinations", "The aim of this prospect i ve clinical 2-year study was to determine whether the placement of the proximal margins of crowns within the zone of the biologic width results in periodontal alterations . In 41 patients , 116 prepared teeth as well as 82 unrestored , healthy contralateral teeth were examined . The following indices were determined before as well as 3 , 6 , 12 , and 24 months after preparation : hygiene index , papillary bleeding index ( PBI ) , and probing depth . After preparation , the distance between the restoration margins and the alveolar crest was measured with a modified periodontal probe on both proximal aspects of each tooth . These values were classified into 3 groups : I = 2 mm . In addition , radiographs were taken directly after cementation of each restoration and after 12 and 24 months . The hygiene index did not significantly vary during the investigation , but PBI increased in all groups . The highest PBI increase was found in group I ; in this group , the most significant increase was found between 3 and 6 months after preparation . The mean probing depth only increased in group I during the first 3 months after preparation on the mesial aspects . Only minor changes were found on the distal aspects of the teeth in group I and on all aspects in groups II and III . No alterations of the bone levels were diagnosed on the radiographs . These results indicate that the location of the restoration margins within the zone of the biologic width may impair the periodontal health of restored teeth" ]	4118467c-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Falls are the main cause of accidental death in persons aged 65 years or older . METHODS Using MEDLINE and previous review s , we search ed for prospect i ve studies investigating risk factors for falls among community-dwelling older people . For risk factors investigated by at least 5 studies in a comparable way , we computed pooled odds ratios ( ORs ) using r and om-effects models , with a test for heterogeneity . RESULTS A total of 74 studies met the inclusion criteria and 31 risk factors were considered , including sociodemographic , mobility , sensory , psychologic , and medical factors and medication use . The strongest associations were found for history of falls ( OR = 2.8 for all fallers ; OR = 3.5 for recurrent fallers ) , gait problems ( OR = 2.1 ; 2.2 ) , walking aids use ( OR = 2.2 ; 3.1 ) , vertigo ( OR = 1.8 ; 2.3 ) , Parkinson disease ( OR = 2.7 ; 2.8 ) , and antiepileptic drug use ( OR = 1.9 ; 2.7 ) . For most other factors , the ORs were moderately above 1 . ORs were generally higher for recurrent fallers than for all fallers . For some factors , there was substantial heterogeneity among studies . For some important factors ( eg , balance and muscle weakness ) , we did not compute a summary estimate because the measures used in various studies were not comparable . CONCLUSIONS This meta- analysis provides comprehensive evidence -based assessment of risk factors for falls in older people , confirming their multifactorial etiology . Some nonspecific indicators of high baseline risk were also strong predictors of the risk of falling	[ "BACKGROUND A st and ard phenotype of frailty was associated with an increased risk of adverse outcomes including mortality in a recent study of older adults . However , the predictive validity of this phenotype for fracture outcomes and across risk subgroups is uncertain . METHODS To determine whether a st and ard frailty phenotype was independently associated with risk of adverse health outcomes in older women and to evaluate the consistency of associations across risk subgroups defined by age and body mass index ( BMI ) , we ascertained frailty status in a cohort of 6724 women > or=69 years and followed them prospect ively for incident falls , fractures , and mortality . Frailty was defined by the presence of three or more of the following criteria : unintentional weight loss , weakness , self-reported poor energy , slow walking speed , and low physical activity . Incident recurrent falls were defined as at least two falls during the subsequent year . Incident fractures ( confirmed with x-ray reports ) , including hip fractures , and deaths were ascertained during an average of 9 years of follow-up . RESULTS After controlling for multiple confounders such as age , health status , medical conditions , functional status , depressive symptoms , cognitive function , and bone mineral density , frail women were subsequently at increased risk of recurrent falls ( multivariate odds ratio=1.38 , 95 % confidence interval [ CI ] , 1.02 - 1.88 ) , hip fracture ( multivariate hazards ratio [MHR]=1.40 , 95 % CI , 1.03 - 1.90 ) , any nonspine fracture ( MHR=1.25 , 95 % CI , 1.05 - 1.49 ) , and death ( MHR=1.82 , 95 % CI , 1.56 - 2.13 ) . The associations between frailty and these outcomes persisted among women > or=80 years . In addition , associations between frailty and an increased risk of falls , fracture , and mortality were consistently observed across categories of BMI , including BMI > or=30 kg/m2 . CONCLUSION Frailty is an independent predictor of adverse health outcomes in older women , including very elderly women and older obese women", "Osteoporosis is responsible for about 1.3 million fractures in the United States each year [ 1 ] . Further , recent research has shown that the risk for most types of fracture in elderly women is related to low bone mass ; thus , the public health impact of osteoporosis may , in fact , be much greater [ 2 ] and is projected to increase over the next several decades [ 3 ] . Postmenopausal estrogen replacement is the current recommended therapy for the prevention of osteoporosis [ 4 ] . However , the use of estrogen is not widespread among elderly women [ 5 ] . Clearly , more options for the prevention of osteoporosis and fracture need to be developed and explored . One option is the use of thiazide diuretics . Thiazide diuretics are known to reduce urinary excretion of calcium [ 6 , 7 ] and may also decrease bone resorption [ 6 ] and bone turnover [ 8 ] . The use of thiazide diuretics has been associated with a reduced risk for fracture , with risk ratios ranging from 0.3 to 0.8 [ 9 - 18 ] . For example , in a casecontrol study that excluded patients taking other drugs thought to affect bone mass , Ray and colleagues [ 15 ] found a 50 % reduction in the risk for hip fracture among patients who had used thiazide diuretics for 6 years . In addition , LaCroix and colleagues [ 16 ] reported a 30 % lower risk for hip fracture in current users compared with nonusers . The Framingham Study also showed a lower risk for hip fracture among users of pure thiazide drugs when compared with those using agents that combined thiazide diuretics with other antihypertensive drugs [ 17 ] . However , all of these studies have been observational , which allows the possibility that users of thiazide diuretics have a lower risk for hip fracture because of other confounding factors . In addition , the more recent data of Heidrich and colleagues [ 19 ] conflict with these results . These investigators found a crude odds ratio for thiazide use and hip fracture of 1.1 , which is not statistically significant . However , when they adjusted for the potentially confounding effects of nursing-home residence ; previous hospitalizations ; history of stroke , alcoholism or organic brain syndrome ; body weight ; leg paralysis ; and use of phenobarbital , corticosteroids , or other diuretics , a significantly increased risk for hip fracture was found among women who reported current use of thiazide diuretics [ 19 ] . No study has prospect ively evaluated the relation between thiazide diuretics and other types of fracture . The mechanism by which thiazide diuretics might protect against hip fracture is not known . Thiazide diuretics may decrease fracture risk by preserving bone mass [ 10 , 11 , 20 - 23 ] . Cross-sectional studies have shown that users of thiazide diuretics have slightly higher cortical and trabecular bone mass than nonusers . Two r and omized clinical studies of the effect of thiazide diuretics on bone loss had conflicting results [ 24 , 25 ] . If thiazide diuretics reduce the risk for hip fracture by slowing bone loss , then these agents should also protect against other types of fracture that are associated with reduced bone mass [ 2 ] . On the other h and , thiazide diuretics could increase the risk for fractures by increasing the risk for falls [ 26 ] . Thiazide diuretics might do this by causing dizziness or postural hypotension [ 27 ] , although the association of diuretic use with falling is not consistent [ 28 ] . More than 90 % of hip fractures are related to falls [ 29 ] . No previous study has included a comprehensive analysis of the effects of thiazide diuretics on bone mass , the risk for falls , and the risk for all fractures in a single population . In our prospect i ve study of 9704 women who were 65 years or older ( the Study of Osteoporotic Fractures ) , we assessed thiazide diuretic use and bone mass at baseline and conducted follow-up examinations every 4 months for the occurrence of fractures and falls . Methods Study Sample From September 1986 through October 1988 , women who were at least 65 years old were recruited for the Study of Osteoporotic Fractures in four areas of the United States : Portl and , Oregon ; Minneapolis , Minnesota ; Baltimore County , Maryl and ; and the Monongahela Valley region near Pittsburgh , Pennsylvania . Age-eligible women were recruited through several sources : health maintenance organizations ; lists of residents that had been compiled for other epidemiologic studies ; jury- selection lists ; voter- registration lists ; and lists of driver 's license holders [ 30 ] . We excluded black women because of their lower incidence of fractures , women who were unable to walk without the assistance of another person , and women who had bilateral hip replacements . Measurement of Bone Mass Bone mineral content ( g/cm ) and density ( g/cm2 ) were measured using single-photon absorptiometry ( OsteoAnalyzer , Siemens-Osteon , Wahiawa , Hawaii ) . Details of these methods have been reported elsewhere [ 30 ] . We scanned three sites : the distal radius , the proximal radius , and the calcaneus . The distal radius is composed of about 60 % cortical bone and 40 % trabecular bone , the proximal radius is about 99 % cortical bone [ 31 ] , and the calcaneus is about 97 % trabecular bone [ 32 ] . The reproducibility of the bone mass measurements , expressed as coefficients of variation , ranged from 1.3 % to 2.0 % among individuals and from 0.4 % to 1.2 % among scanners [ 30 ] . Diuretic Use Information on diuretic use was obtained at the baseline clinic interview . Participants were asked to bring all current medications to the clinic for verification . In addition , pictures of tablets were presented to participants to assist them in the re collection of previously prescribed diuretics . Diuretics , including combination drugs , were classified as thiazide diuretics according to the American Medical Association drug evaluations [ 33 ] . Separate histories were obtained from participants for use of thiazide and nonthiazide diuretics . Chlorthalidone was classified as a thiazide diuretic because its effects on calcium excretion are similar to those of thiazide diuretics . Analyses in which chlorthalidone was not considered as a thiazide diuretic yielded similar results . Women were asked whether they had ever taken diuretics ; at what age they had started taking diuretics ; whether they were currently using diuretics and , if not , when they had stopped ; whether they took diuretics the entire time or stopped for a few years ; and the name of the medication they were currently using . Duration of diuretic use was calculated as the total number of years that they reported using diuretics . No information was collected on dose at the baseline visit , but dose-related data were recorded at the first annual telephone interview . Information on duration of thiazide diuretic use was missing in 15 women . These women were excluded from all analyses . Other Measurements Reported health status , type of menopause , alcohol consumption , and cigarette smoking were assessed using a question naire that was review ed with the participant by a trained interviewer . Women were considered to have had a surgical menopause if they reported having had a bilateral oophorectomy at the age at which they stopped menstruating . Regarding alcohol consumption , participants were asked how much they had consumed during the past 30 days and how many times they had consumed three or more drinks per day and five or more drinks per day during the past 30 days . The measure of alcohol consumption used in our study was drinks per week , which was adjusted for atypical drinking , particularly heavy drinking over the last 30 days . Dietary calcium was assessed by a food frequency question naire and an interview using st and ardized food models to estimate portion sizes [ 34 ] . In our study , total calcium intake included dietary and supplemental calcium . Women were also asked if they had ever taken the following medications : thyroid hormones , medicine for seizures , vitamin D or multivitamins containing vitamin D , TUMS , calcium supplements , antacids , prednisone , cortisone , other steroid pills , birth control pills , estrogen pills , estrogen skin patches , estrogen vaginal cream or suppositories , estrogen injections , and progestins . Information was obtained on current use , duration of use , and specific drug and dosage used for the longest period . Functional status was measured by a respondent 's answers to questions about her ability to perform six instrumental activities of daily living by herself and without using special aids or equipment . These activities were as follows : walking two or three blocks outside on level ground ; climbing up 10 steps without stopping ; walking down 10 steps ; preparing one 's own meals ; doing heavy housework ; and doing one 's own shopping for groceries or clothes . The measure used in these analyses is the total number of activities ( ranging from 0 to 6 ) that a woman reported she was unable to do or had difficulty doing . Additionally , women were asked to rate their health status as very good , good , fair , poor , or very poor . During the clinic examination , body weight was measured ( after removal of shoes and heavy outer clothing ) using a balance beam scale . Height was measured ( after removal of shoes ) using a Harpenden stadiometer ( Holtain , Ltd. , Dyved , United Kingdom ) . Height and weight were used to calculate the body mass index ( kg/m2 ) . Ascertainment of Prevalent Vertebral Deformities The prevalence of vertebral deformities as shown by lateral thoracic and lumbar spine films was obtained on 2992 women ( 31 % of the cohort ) who were between 65 and 70 years old . The methods used to identify vertebral deformities have been described previously [ 35 ] . In summary , six points for each vertebral body , T4 through L4 , were marked with a translucent digitizer . We calculated three heights ( anterior , posterior , and middle ) and three ratios : anterior-to-posterior height ( wedge ) ; mid-to-posterior height ( endplate ) ; and the posterior height of each vertebra to the posterior height of the adjacent vertebrae ( crush ) . We classified a vertebral body", "Background and Purpose — The association between cerebral white matter lesions ( WMLs ) and the risk of falls in older people is uncertain , with no supporting prospect i ve evidence . We aim ed to determine the risk of incident falls associated with WML volume , and the interactions between WML volume , gait , and other sensorimotor factors leading to falls . Methods — We conducted a prospect i ve , population -based study ( n=294 , mean age 72.3 years , independently mobile ) . Volumetric MRI , computerized gait measures , and sensorimotor measures of falls risk were obtained at baseline . Incident falls were recorded prospect ively over a 12-month period . Using regression modeling , we estimated the risk of incident falls associated with baseline WML volume . Results — Increasing baseline WML volume was independently associated with any incident fall ( P=0.01 ) and multiple incident falls ( P=0.02 ) . The risk of incident falls was doubled in people with lesion volumes in the highest quintile of its distribution compared with the lowest ( adjusted relative risk , 2.32 ; 95 % CI , 1.28–4.14 ) . Greater lesion volume was also associated with poorer gait and greater gait variability ( both P of WML volume on the risk of falls was magnified in people with poorer quadriceps muscle strength ( P=0.03 ) and greater gait variability ( P=0.001 ) . Conclusions — These data provide the first prospect i ve evidence to our knowledge demonstrating that WMLs are strong risk factors for falls in the general older population . WMLs present potential therapeutic targets for interventional trials in falls prevention", "CONTEXT Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population . OBJECTIVE The objective of the study was to examine the association between creatinine clearance ( CrCl ) and the incidence of falls and fallers in groups treated with placebo , calcitriol , estrogen therapy (ET)/estrogen + progestin therapy ( HT ) , and calcitriol + ET/HT . DESIGN This was a 3-yr , double-blind , placebo-controlled study design ed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc . SETTING The study was conducted at an academic outpatient center . PARTICIPANTS Four hundred eighty-nine normal elderly women aged 65 - 77 yr ; 415 women completed the study . INTERVENTION Subjects were r and omized to placebo , calcitriol 0.25 mug twice a day , ET daily ( conjugated equine estrogens 0.625 mg ) , HT ( conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg ) and calcitriol + ET/HT . MAIN OUTCOME MEASURES Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater . RESULTS Calcitriol treatment decreased the number of fallers and falls . Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group ( P = 0.007 ) . In the low CrCl group ( rate of falls decreased on calcitriol by 53 % [ 95 % confidence interval ( CI ) -71 % to -22 % ; P = 0.003 ] , calcitriol + ET/HT by 61 % ( 95 % CI -76 % to -37 % ; P = 0.001 ) , and ET/HT by 25 % ( 95 % CI : -55 % to + 24 % ; not significant ) . Calcitriol reduced the rate of falls by 30 % ( 95 % CI -49 % to -4 % ; P = 0.027 ) in the CrCl 60 ml/min or greater group . CONCLUSION Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function ( < 60 ml/min ) and frequent fallers", "It is not clear which specific cognitive function is strongest related to falls . To investigate this , not only \" general cognitive functioning , \" but also \" nonverbal and abstract reasoning , \" \" information processing speed , \" and \" immediate memory \" were related to falls . Furthermore , relevant effect modifiers , confounders , and mediators were identified . This study was performed within the Longitudinal Aging Study Amsterdam ( LASA ) , a multidisciplinary , prospect i ve cohort study . In this study ( n = 1437 ) , an interaction between \" immediate memory \" and age was found . In persons aged 75 years and over , \" immediate memory , \" as measured by the 15 Words Test , showed to be an independent risk factor for falls . Part of this relationship was explained by the mediating effects of activity , mobility , and grip strength . The association between the other cognitive functions and falls was only statistically significant in univariate analysis . We conclude that \" immediate memory \" is an independent risk factor for recurrent falls in persons aged 75 years and older", "BACKGROUND AND OBJECTIVES To evaluate the incidence of falls according to socio-demographic and health factors , and to determine their physical , psychological and social consequences . SUBJETS AND METHOD : Population -based prospect i ve study , which included a representative cohort of 448 elderly community-dwellers , aged 65 or more living in the city of Mataró ( Spain ) . We made a baseline evaluation , which was repeated after a one-year follow up , consisting of a st and ardized question naire on socio-demographic characteristics , physical activity , tests of physical and cognitive function , history of falls during the previous year , the Falls Efficacy Scale , and associated chronic conditions . Follow-up interviews at intervals of one month over 12 months , consisting of a st and ardized question naire aim ed at detecting and describing any fall occurred during the previous month . RESULTS 25.1 % ( 95 % CI , 18.8 - 31.4 ) of males and 37.0 % ( 95 % CI , 31.2 - 42.8 ) of females fell . Multiple falls were observed in 3.8 % of men and 10.9 % of women . 203 falls were reported , providing a crude incidence rate of 30.9 falls per 100 men-years ( 95 % CI , 23.3 - 41.0 ) and 56.5 falls per 100 women-years ( 95 % CI , 46.5 - 68.8 ) . A positive association with falls was found with age , reduced physical and cognitive function , associated chronic conditions and previous falls . 71.1 % of falls had physical consequences , with 7.7 % of fractures , and 21.7 % needed medical aid . 64.4 % of fallers feared of falling again . CONCLUSIONS Our study shows a pattern of high incidence of falls among the elderly living in the Spanish non-institutionalized community . Our data confirm that adverse consequences derived from the falls are frequent and often severe , which makes falls one of the major problems of elderly people", "Introduction The aim of the prospect i ve study reported here was to develop a risk profile that can be used to identify community-dwelling elderly at a high risk of recurrent falling . Material s and methods The study was design ed as a 3-year prospect i ve cohort study . A total of 1365 community-dwelling persons , aged 65 years and older , of the population -based Longitudinal Aging Study Amsterdam participated in the study . During an interview in 1995/1996 , physical , cognitive , emotional and social aspects of functioning were assessed . A follow-up on the number of falls and fractures was conducted during a 3-year period using fall calendars that participants filled out weekly . Recurrent fallers were identified as those who fell at least twice within a 6-month period during the 3-year follow-up . Results The incidence of recurrent falls at the 3-year follow-up point was 24.9 % in women and 24.4 % in men . Of the respondents , 5.5 % reported a total of 87 fractures that result ed from a fall , including 20 hip fractures , 21 wrist fractures and seven humerus fractures . Recurrent fallers were more prone to have a fall-related fracture than those who were not defined as recurrent fallers ( 11.9 % vs. 3.4 % ; OR : 3.8 ; 95 % CI : 2.3–6.1 ) . Backward logistic regression analysis identified the following predictors in the risk profile for recurrent falling : two or more previous falls , dizziness , functional limitations , weak grip strength , low body weight , fear of falling , the presence of dogs/cats in the household , a high educational level , drinking 18 or more alcoholic consumptions per week and two interaction terms ( high education × 18 or more alcohol consumptions per week and two or more previous falls × fear of falling ) ( AUC=0.71 ) . Discussion At a cut-off point of 5 on the total risk score ( range 0–30 ) , the model predicted recurrent falling with a sensitivity of 59 % and a specificity of 71 % . At a cut-off point of 10 , the sensitivity and specificity were 31 % and 92 % , respectively . A risk profile including nine predictors that can easily be assessed seems to be a useful tool for the identification of community-dwelling elderly with a high risk of recurrent falling ", "Methods of prevention of falls in the home may differ for healthy and frail individuals . We therefore sought to determine whether measures of health and functioning in older persons are more useful in predicting falls at home not involving home hazards ( non-environmental falls ) than falls at home related to home hazards ( environmental falls ) , and whether these relationships differ among those who fell once and those who fell multiple times during follow-up . Data for this analysis are from a 1-year prospect i ve cohort study of 325 community-dwelling volunteers aged 60–93 years who had fallen during the year before baseline . In general , associations were stronger between poor functional ability and non-environmental falls than between poor functional ability and environmental falls . Independent predictors of non-environmental first falls during follow-up included Parkinson 's disease ( adjusted odds ratio ( AOR ) 7.66 , 95 % confidence interval ( 95 % CI ) 1.15–51.1 ) and being home alone 10 or more hours per day ( AOR 2.36 , 95 % CI 1.20–4.61 ) ; independent predictors of environmental first falls during follow-up included arthritis ( AOR 2.60 , 95 % CI 1.32–5.09 ) and poor depth perception ( AOR 0.73 , 95 % CI 0.59–0.89 , for each unit increase in depth perception score ) . Also , associations between poor function and falls were generally stronger among participants who fell repeatedly than among individuals who fell only once during the follow-up year . In conclusion , poor function predisposes to non-environmental falls at home in older persons and , to a lesser extent , environmental falls in those who fall repeatedly . Certain functional characteristics such as poor depth perception may predispose to environmental falls to a greater extent than do other disabilities", "OBJECTIVES we studied visual acuity ( VA ) and co-existing hearing impairment and poor st and ing balance as predictors of falls . DESIGN prospect i ve study with 1-year follow-up . SETTING research laboratory and residential environment . PARTICIPANTS 428 women aged 63 - 76 years from the Finnish Twin Study on Aging . MEASUREMENTS participants were followed up for incidence of falls over 1 year . VA , hearing ability and st and ing balance were assessed at the baseline . The incidence rate ratios ( IRR ) for falls were computed using the negative binomial regression model . RESULTS during the follow-up , 47 % of participants experienced a fall . After adjusting for age and interdependence of twin sisters , participants with vision impairment ( VA of higher , but non-significant , risk for falls compared to persons with normal vision ( IRR 1.5 , 95 % CI 0.6 - 4.2 ) . Co-existing vision impairment and impaired balance increased the risk ( IRR 2.7 , 95 % CI 0.9 - 8.0 ) , as also did co-existing vision and hearing impairment ( IRR 4.2 , 95 % CI 1.5 - 11.3 ) , compared to those with normal vision . Among persons with all three impairments , the IRR for falls increased to 29.4 ( 95 % CI 5.8 - 148.3 ) compared to participants with good vision . CONCLUSION the impact of vision impairment on fall risk was higher when accompanied with other sensory and balance impairments , probably because the presence of other impairments prevented the reception of compensatory information about body posture and environment being received from other sensory sources . When aim ing to prevent falls and their consequences in older people , it is important to check whether poor vision is accompanied with other impairments", "BACKGROUND Gonadal steroid levels decline with age in men . Whether low testosterone levels affect the development of common age-related disorders , including physical functioning and falling , is unclear . METHODS This longitudinal , observational follow-up study sought to determine whether low testosterone levels are associated with physical performance and fall risk in older men . A total of 2587 community-based men aged 65 to 99 years were selected using a stratified r and om sampling scheme from a study cohort of 5995 volunteers . Bioavailable testosterone and estradiol levels and physical performance measures were determined from baseline . Incident falls were ascertained every 4 months during 4 years of follow-up . Generalized estimating equations were used to estimate risk ratios for the relation of sex steroids to falls . RESULTS Fifty-six percent of the men reported at least 1 fall ; many fell frequently . Lower bioavailable testosterone levels were associated with increased fall risk . Men with testosterone levels in the lowest quartile had a 40 % higher fall risk than those in the highest quartile . The effect of low testosterone levels was most apparent in younger men ( 65 - 69 years ) ( relative risk , 1.8 ; 95 % confidence interval , 1.2 - 2.7 ) ; testosterone level was not associated with falls in the oldest men ( > /=80 years ) . Lower testosterone concentrations were associated with reduced physical performance . However , the association between low testosterone levels and fall risk persisted despite adjustment for performance . CONCLUSIONS Falls were common among older men . Fall risk was higher in men with lower bioavailable testosterone levels . The effect of testosterone level was independent of poorer physical performance , suggesting that the effect of testosterone on fall risk may be mediated by other and rogen actions", "OBJECTIVE To determine the association between changes in visual acuity ( VA ) and frequent falls in older women . DESIGN Prospect i ve cohort study . PARTICIPANTS Two thous and two elderly community-residing women participating in the Study of Osteoporotic Fractures with measurements of VA at baseline and a follow-up examination 4 to 6 years later ( mean of 5.6 years ) . METHODS Binocular VA with habitual correction was measured under st and ard illumination using Bailey-Lovie charts at baseline and fourth examinations . Change in VA was stratified into 5 categories : no change or VA gain , loss of 1 to 5 letters , loss of 6 to 10 letters , loss of 11 to 15 letters , and loss of > 15 letters . A separate analysis considered decline in VA as the loss of > or=10 letters ( > or=2 lines ) on the Bailey-Lovie acuity measure between baseline and follow-up examinations . MAIN OUTCOME MEASURES Data on falls were obtained from postcards sent every 4 months after the follow-up examination . Frequent falling was defined as > or=2 falls during a 1-year period after the follow-up examination . RESULTS Compared with women with stable or improved VA , women with declining acuity had significantly greater odds of experiencing frequent falling during the subsequent year . Odds ratios after adjustment for baseline acuity and other confounders were 2.08 ( 95 % confidence interval [ CI ] : 1.39 - 3.12 ) for loss of 1 to 5 letters , 1.85 ( 95 % CI : 1.16 - 2.95 ) for loss of 6 to 10 letters , 2.51 ( 95 % CI : 1.39 - 4.52 ) for loss of 11 to 15 letters , and 2.08 ( 95 % CI : 1.01 - 4.30 ) for loss of > 15 letters . In the analysis of visual decline defined as a loss of > or=10 letters , heightened risk of frequent falling was evident in each of 2 subgroups defined by splitting the sample on baseline VA , with borderline significant evidence of a more pronounced effect in those women with baseline VA of 20/40 or worse ( P value for interaction , 0.083 ) . CONCLUSIONS Loss of vision among elderly women increases the risk of frequent falls . Prevention or correction of visual loss may help reduce the number of future falls", "OBJECTIVE To determine the prevalence of impaired vision , peripheral sensation , lower limb muscle strength , reaction time , and balance in a large community-dwelling population of women aged 65 years and over , and to determine whether impaired performances in these tests are associated with falls . DESIGN One-year prospect i ve study . SETTING Conducted as part of the R and wick Falls and Fractures Study , in Sydney , Australia . PARTICIPANTS Four hundred fourteen women aged 65 to 99 years ( mean age 73.7 years , SD = 6.3 ) were r and omly selected from the community ; 341 of these women were included in the 1-year prospect i ve study . MAIN RESULTS The prevalence of impairment in all tests increased with age . In the year following assessment , 207 subjects ( 60.7 % ) experienced no falls , 63 subjects ( 18.5 % ) fell one time only , and 71 subjects ( 20.8 % ) fell on two or more occasions . After controlling for age , multiple falling was associated with low contrast visual acuity and contrast sensitivity , poor vibration sense and proprioception , reduced lower limb strength , slow reaction time , and impaired balance , as indicated by four sway tests and two clinical stability measures . Discriminant function analysis identified visual contrast sensitivity , proprioception in the lower limbs , quadriceps strength , reaction time , and sway on a compliant ( foam rubber ) surface with the eyes open as the variables that significantly discriminated between subjects who experienced multiple falls and subjects who experienced no falls or one fall only ( Wilks ' lambda = 0.73 ( P and institutional setting and indicate that the test procedure aids in the identification of older community-dwelling women at risk of falls", "OBJECTIVE To determine whether older women with diabetes have an increased risk of falls and whether known risk factors for falls account for any increased risk . RESEARCH DESIGN AND METHODS This prospect i ve cohort study included 9,249 women > or = 67 years of age enrolled in the Study of Osteoporotic Fractures . Diabetes was determined by question naire at baseline . Physical performance was measured at the second examination . Subsequently , falls were ascertained every 4 months by postcard . RESULTS A total of 629 ( 6.8 % ) women had diabetes , including 99 who used insulin . During an average of 7.2 years , 1,640 women ( 18 % ) fell more than once a year . Diabetes , stratified by insulin use , was associated with an increased risk of falling more than once a year ( age-adjusted odds ratio [ OR ] 1.68 [ 95 % CI 1.37 - 2.07 ] for non-insulin-treated diabetes ; age-adjusted OR 2.78 [ 1.82 - 4.24 ] for insulin-treated diabetes ) . In the first 2 years of follow-up , women with diabetes were not more likely to fall than women without diabetes ( 44 vs. 42 % ; P = 0.26 ) , but they had more falls ( 3.1 vs. 2.4 ; P risk factors for falls , which appeared to account for the increased risk of falls associated with non-insulin-treated diabetes ( adjusted OR 1.18 [ 0.87 - 1.60 ] ) but not insulin-treated diabetes ( adjusted OR 2.76 [ 1.52 - 5.01 ] ) . CONCLUSIONS Older women with diabetes have an increased risk of falling , partly because of the increased rates of known fall risk factors , and may benefit from interventions to prevent falls . Further research is needed to determine whether diabetes treatment reduces fall risk", "BACKGROUND Little is known about the prevalence of falls and the related risk factors in the general population of community-living older people in Germany . OBJECTIVES To assess the prevalence and related predictors of different types of falls in a sample of community-dwelling 65 years and older people in Germany living in a metropolitan area . Study design and setting prospect i ve cohort study in 622 community dwelling people aged > or = 65 years . RESULTS A total of 107 persons ( 17.2 % ) reported falling at least once ( occasional fallers ) , while 36 ( 5.7 % ) experienced two or more falls ( recurrent fallers ) in the last 6 months . Main predictors for all fallers were age ( OR 1.8 ; 95 % CI 1.1 - 3.0 ) , being female ( OR 1.7 ; 95 % CI 1.1 - 2.2 ) , living alone ( OR 1.9 ; 95 % CI 1.2 - 2.9 ) , poor health status ( OR 3.3 ; 95 % CI 2.1 - 5.3 ) , varifocals ( OR 1.7 ; 95 % CI 1.0 - 3.1 ) , disturbance of memory ( OR 1.7 ; 95 % CI 1.0 - 3.0 ) , depression ( OR 4.8 ; 95 % CI 2.5 - 9.2 ) , sleep disturbances ( OR 2.7 ; 95 % CI 1.7 - 4.3 ) , incontinence ( OR 2.1 ; 95 % CI 1.3 - 4.9 ) , dizziness ( OR 3.0 ; 95 % CI 1.9 - 5.0 ) , 3 medical conditions or more ( OR 3.3 ; 95 % CI 2.1 - 5.1 ) , lower physical functioning and mobility . Two of the strongest predictors were reported falls ( OR 4.9 ; 95 % CI 3.1 - 7.7 ) and recurrent falls ( OR 10.0 ; 95 % CI 5.0 - 20.0 ) in the last 6 months . CONCLUSION Older adults living at home should be screened for falls in history and problems in gait and mobility in any anamnesis to identify those who are at risk for falls", "OBJECTIVES To develop a classification tree for predicting the risk of recurrent falling in community-dwelling older persons using tree-structured survival analysis ( TSSA ) . DESIGN A prospect i ve cohort study . SETTING A community in the Netherl and s. PARTICIPANTS One thous and three hundred sixty-five community-dwelling older persons ( > /=65 ) from the Longitudinal Aging Study Amsterdam ( LASA ) . MEASUREMENTS In 1995 , physical , cognitive , emotional , and social aspects of functioning were assessed . Subsequently , a prospect i ve fall follow-up , specifically on recurrent falls ( two falls within 6 months ) was conducted for 3 years . RESULTS The classification tree included 11 end groups differing in risk of recurrent falling based on a minimum of two and a maximum of six predictors . The first split in the tree involved two or more falls versus fewer than two falls in the year preceding the interview . Respondents with two or more falls in the year preceding the interview ( n=193 ) and with at least two functional limitations ( n=98 ) had a 75 % risk of becoming a recurrent faller , whereas respondents with fewer than two functional limitations were further divided into a group with regular dizziness ( n=11 , risk of 68 % ) and a group with no regular dizziness ( n=84 , risk of 30 % ) . In respondents with fewer than two falls in the year preceding the interview ( n=1,172 ) , the risk of becoming a recurrent faller varied between 9 % and 70 % . Predictors in this branch of the tree were low performance , low h and grip strength , alcohol use , pain , high level of education , and high level of physical activity . CONCLUSION This classification tree included 11 end groups differing in the risk of recurrent falling based on specific combinations of a maximum of six easily measurable predictors . The classification tree can identify subjects who are eligible for preventive measures in public health strategies", "Background The European and American guidelines state the need for echocardiography in patients with syncope . 50 % of older adults with syncope present with a fall . Nonetheless , up to now no data have been published addressing echocardiographic abnormalities in older fallers . Method and Findings In order to determine the association between echocardiographic abnormalities and falls in older adults , we performed a prospect i ve cohort study , in which 215 new consecutive referrals ( age 77.4 , SD 6.0 ) of a geriatric outpatient clinic of a Dutch university hospital were included . During the previous year , 139 had experienced a fall . At baseline , all patients underwent routine two-dimensional and Doppler echocardiography . Falls were recorded during a three-month follow-up . Multivariate adjustment for confounders was performed with a Cox proportional hazards model . 55 patients ( 26 % ) fell at least once during follow-up . The adjusted hazard ratio of a fall during follow-up was 1.35 ( 95 % CI , 1.08–1.71 ) for pulmonary hypertension , 1.66 ( 95 % CI , 1.01 to 2.89 ) for mitral regurgitation , 2.41 ( 95 % CI , 1.32 to 4.37 ) for tricuspid regurgitation and 1.76 ( 95 % CI , 1.03 to 3.01 ) for pulmonary regurgitation . For aortic regurgitation the risk of a fall was also increased , but non-significantly ( hazard ratio , 1.57 [ 95 % CI , 0.85 to 2.92 ] ) . Trend analysis of the severity of the different regurgitations showed a significant relationship for mitral , tricuspid and pulmonary valve regurgitation and pulmonary hypertension . Conclusions Echo(Doppler)cardiography can be useful in order to identify risk indicators for falling . Presence of pulmonary hypertension or regurgitation of mitral , tricuspid or pulmonary valves was associated with a higher fall risk . Our study indicates that the diagnostic work-up for falls in older adults might be improved by adding an echo(Doppler)cardiogram in selected groups", "OBJECTIVES To examine whether anemia is associated with a higher incidence of recurrent falls . DESIGN Prospect i ve cohort study . SETTING Community-dwelling sample in The Netherl and s. PARTICIPANTS Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam . MEASUREMENTS Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men . Falls were prospect ively determined using fall calendars that participants filled out weekly for 3 years . Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up . RESULTS Of the 394 persons , 11.9 % ( 18 women and 29 men ) had anemia . The incidence of recurrent falls was 38.3 % of anemic persons versus 19.6 % of nonanemic persons ( P=.004 ) . After adjustment for sex , age , body mass index , and diseases , anemia was significantly associated with a 1.91 times greater risk for recurrent falls ( 95 % confidence interval=1.09 - 3.36 ) . Poor physical function ( indicated by muscle strength , physical performance , and limitations ) partly mediated the association between anemia and incidence of recurrent falls . CONCLUSION Late-life anemia is common and associated with twice the risk of recurrent falls . Muscle weakness and poor physical performance appear to partly mediate this association", "The objective of this study was to identify easily measurable predictors for falls , recurrent falls , and fractures using a population -based prospect i ve cohort study of 1469 elderly , born before 1931 , in three regions of the Netherl and s. The baseline at-home interview was in 1992 . In 1995 , falls experienced in the preceding year and fractures over the preceding 38-month period were registered . In a period of 1 year , 32 % of the participants fell at least once , and 15 % fell two or more times . The rate of recurrent falls was similar in men and women up until the age of 75 years . The total number of fractures was 85 , including 23 wrist fractures , 12 hip fractures , and 9 humerus fractures . The incidence density per 1000 person-years for any fracture was 25.1 ( 95 % confidence interval [ CI ] , 18.9 - 31.4 ) for women and 8.2 ( 95 % CI , 4.5 - 12.0 ) for men , respectively . Multiple logistic regression identified urinary incontinence , impaired mobility , use of analgetics , and use of antiepileptic drugs as the predictors most strongly associated with recurrent falls . Female gender , living alone , past fractures , inactivity , body height , and use of analgetics proved to be the predictors most strongly associated with fractures . The probabilities of recurrent falls were 4.7 % ( 95 % CI , 2.9 - 7.5 % ) to 59 . 2 % ( 95 % CI , 24.1 - 86.9 % ) with zero to four predictors , respectively . The probability of fractures ranged from 0.0 % ( 95 % CI , 0.0 - 0.4 % ) without any of the identified predictors to 12.9 % ( 95 % CI , 4.4 - 32 . 2 % ) with all six predictors present . Our study shows that the risk of recurrent falls and of fractures can be predicted using up to , respectively , four and six easily measurable predictors . This study emphasizes the importance of impaired mobility and inactivity as predictors for falls and fractures", "Background .Identifying and eliminating environmental hazards in the home has high face validity but little empirical support for fall prevention . Objective .The objective of this study was to determine whether environmental hazards increase the risk of nonsyncopal falls in the homes of community-living older persons . Research Design .This was a prospect i ve cohort study . Participants .The study included 1,088 men and women from a probability sample of 1,103 persons ≥72 years of age . Measures .A room-by-room assessment for 13 potential trip or slip hazards was completed at baseline and 1 year later by a trained research nurse using a st and ard instrument . Falls were ascertained monthly for 3 years using a fall calendar and follow-up phone calls . Results .The numbers of participants with a nonsyncopal fall ( by room ) were as follows : 88 ( kitchen ) , 144 ( living room ) , 41 ( hallway ) , 136 ( bedroom ) , and 59 ( bathroom ) . The risk of a nonsyncopal fall was significantly elevated for only 1 of the 13 trip or slip hazards . For exposure to ≥1 hazards per room , the relative risks adjusted for age , gender , and housing type were 0.91 ( 95 % CI , 0.58–1.43 ) for the kitchen , 1.30 ( 95 % CI , 0.92–1.83 ) for the living room , 1.73 ( 95 % CI , 0.93–3.22 ) for the hallway , 1.29 ( 95 % CI , 0.90–1.84 ) for the bedroom , and 0.57 ( 95 % CI , 0.32–1.00 ) for the bathroom . No consistent association was found between the 13 trip or slip hazards and nonsyncopal falls , even after participants were categorized by impairments in vision , balance/gait , and cognition . Conclusions .Our findings do not support an association between environmental hazards and nonsyncopal falls", "INTRODUCTION This is the first prospect i ve longitudinal study carried out in a Chinese elderly population with the objective of identifying the incidence and predictors of falls . MATERIAL S AND METHODS This is a population -based cohort study in Hong Kong with 1517 ambulatory elderly Chinese recruited using a multi-stage sampling method . Baseline data on demographic , comorbid diseases , drugs , Activities of Daily Living ( ADL ) [ Barthel Index and Lawton 's Instrumental Activities of Daily Living ( IADL ) ] , Geriatric Depression Scale ( GDS-15 ) , cognitive assessment by the Abbreviated Mental Test ( AMT ) , fear of falling , self-perceived mobility problem , h and grip strength , lower limb power , balance and gait tests were performed . Every subject was followed up for 1 year . RESULTS Four hundred and one falls occurred in 294 fallers ( 19.3 % ) over 1 year of follow-up . The prevalence of falls and recurrent falls were 19.3 % and 4.75 % , respectively . The incidences of falls ( i.e. , the fall events ) were 220 , 324 and 270 per 1000 person-years for men , women and both gender , respectively . The independent predictors of falls were previous history of falls , advancing age , Parkinson 's disease , knee extension power and gait speed . The independent predictors of recurrent falls were previous history of falls , self-perceived mobility problem , the knee extension strength and the Total Mobility Score of the Tinetti Balance and Gait Evaluation . CONCLUSIONS The incidence of falls in the Chinese elderly was 270 per 1000 person-years . History of falls , old age , Parkinson 's disease , decreased lower limb power and impairment in balance and gait function were important independent predictors of falls or recurrent falls in the Chinese elderly . Effective fall prevention programmes targeted at improving these risk factors for falls should be developed for the Chinese elderly in Hong Kong and Asia", "In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement", "BACKGROUND Falls are common in community-dwelling elderly persons and are a frequent source of morbidity . Simple indices to prospect ively stratify people into categories at different fall-risk would be useful to health care practitioners . Our goal was to develop a fall-risk index that discriminated between people at high and low risk of falling . METHODS We evaluated the risk of falling over a one-year period in 557 elderly persons ( mean age 81.6 ) living in a retirement community . On the baseline interview , we asked subjects if they had fallen in the previous year and evaluated risk factors in six additional conceptual categories . On the follow-up interview one year later , we again asked subjects if they had fallen in the prior year . We evaluated risk factors in the different conceptual categories and used logistic regression to determine the independent predictors of falling over a one-year period . We used these independent predictors to create a fall-risk index . We compared the ability of a prior falls history with other risk factors and with the combination of a falls history and other risk factors to discriminate fallers from nonfallers . RESULTS A fall in the previous year ( OR = 2.42 , 95 % CI = 1.49 - 3.93 ) , a symptom of either balance difficulty or dizziness ( OR = 1.83 , 95 % CI = 1.16 - 2.89 ) , or an abnormal mobility exam ( OR = 2.64 , 95 % CI = 1.64 - 4.26 ) were independent predictors of falling over the subsequent year . These three risk factors together ( c statistic = .71 ) discriminated fallers from nonfallers better than previous history of falls alone ( c statistic = .61 ) or the symptomatic and exam risk factors alone ( c statistic = .68 ) . When combined into a risk index , the three independent risk factors stratify people into groups whose risk for falling over the subsequent year ranges from 10 % to 51 % . CONCLUSION A history of falling over the prior year , a risk factor that can be obtained from a clinical history ( balance difficulty or dizziness ) , and a risk factor that can be obtained from a physical exam ( mobility difficulty ) stratify people into groups at low and high risk of falling over the subsequent year . This risk index may provide a simple method of assessing fall risk in community-dwelling elderly persons . However , it requires validation in other subjects before it can be recommended for widespread use", "OBJECTIVES To examine the relationship between binocular visual field loss and the risk of incident frequent falls in older white women . DESIGN A multicenter , prospect i ve cohort study . SETTING Four clinic centers within the United States in Baltimore , Maryl and ; Minneapolis , Minnesota ; Portl and , Oregon ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS Four thous and seventy-one community-dwelling white women aged 70 and older participating in the Study of Osteoporotic Fractures . MEASUREMENTS Primary outcome was incident frequent falls , defined as two or more falls within 1 year . Primary risk factors were binocular visual field loss , distance visual acuity in the better eye , and contrast sensitivity at low spatial frequency in the better eye . RESULTS Of 4,071 women , 409 ( 10 % ) had severe binocular visual field loss at the eye examination , and 643 ( 16 % ) experienced frequent falls within 1 year after their eye examination . Severe binocular visual field loss was significantly associated with frequent falls when adjusting for age , study site , and cognitive function ( odds ratio=1.50 , 95 % confidence interval=1.11 - 2.02 ) . The data showed a trend for increasing odds of two or more falls with greater binocular visual field loss ( P older white women with severe binocular visual field loss , 33.3 % of frequent falls were attributable to visual field loss . CONCLUSION Women with binocular visual field loss are at greater risk of future frequent falls . Screening for binocular visual field loss may identify individuals at high risk of falling", "OBJECTIVES To test the association between self-reported sleep and nap habits and risk of falls and fractures in a large cohort of older women . DESIGN Study of Osteoporotic Fractures prospect i ve cohort study . SETTING Clinical centers in Baltimore , Maryl and ; Minneapolis , Minnesota ; Portl and , Oregon ; and the Monongahela Valley , near Pittsburgh , Pennsylvania . PARTICIPANTS Eight thous and one hundred one community-dwelling Caucasian women aged 69 and older ( mean 77.0 ) . MEASUREMENTS Sleep and nap habits were assessed using a question naire at the fourth clinic visit ( 1993/94 ) . Fall frequency during the subsequent year was ascertained using tri-annual question naire . Incident hip and nonspinal fractures during 6 years of follow-up were confirmed using radiographic reports . RESULTS Five hundred fifty-three women suffered hip fractures , and 1,938 suffered nonspinal fractures . In multivariate models , women who reported napping daily had significantly higher odds of suffering two or more falls during the subsequent year ( odds ratio=1.32 , 95 % confidence interval (CI)=1.03 - 1.69 ) and were more likely to suffer a hip fracture ( hazard ratio (HR)=1.33 , 95 % CI=0.99 - 1.78 ) than women who did not nap daily . Those sleeping at least 10 hours per 24 hours had a higher risk of nonspinal fracture than ( HR=1.26 , 95 % CI=1.00 - 1.58 ) and a similar but nonsignificant increased risk of hip fracture to ( HR=1.43 , 95 % CI=0.95 - 2.15 ) those who reported sleeping between 8 and 9 hours . CONCLUSION Self-reported long sleep and daily napping are associated with greater risk of falls and fractures in older women . Interventions to improve sleep may reduce their risk of falls and fractures . Future research is needed to determine whether specific sleep disorders contribute to these relationships", "OBJECTIVES To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults . DESIGN Cross-sectional and longitudinal analyses . SETTING Four U.S. communities . PARTICIPANTS A total of 5,841 older adults enrolled in the Cardiovascular Health Study , an ongoing , population -based , prospect i ve cohort study , participated . MEASUREMENTS Self-reported alcohol consumption at baseline , self-reported frequent falls at baseline , and the 4-year risk of falls of participants who denied frequent falls at baseline . RESULTS Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls ( adjusted odds ratio in consumers of 14 or more drinks per week=0.41 ; 95 % confidence interval (CI)=0.14 - 1.17 ; P for trend=.06 ) , but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25 % higher risk in consumers of 14 or more drinks per week ( 95 % CI=3 - 52 % ; P for trend=.07 ) . Similar results were found in analyses stratified by age , sex , race , and physical activity . CONCLUSION Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults . Cross-sectional studies may fail to identify this risk of heavier drinking , perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies . However , because this study relied upon annual reporting of falls , further prospect i ve studies should be conducted to confirm these findings", "OBJECTIVES To determine whether musculoskeletal pain increased risk for falls in older women with disabilities . DESIGN Prospect i ve population -based cohort study . SETTING The city and county of the eastern area of Baltimore . PARTICIPANTS One thous and two women aged 65 and older , participants in the Women 's Health and Aging Study , representing the one-third of older women who were living at home with disabilities , followed semiannually for 3 years beginning in 1991 . MEASUREMENTS Pain was categorized into four groups according to severity and location . Widespread pain was defined as pain in the upper and lower extremities and in the axial skeletal region , with moderate to severe pain in at least one region ( > or = 4 on a 10-point numeric rating scale , 10 = excruciating pain ) . Moderate to severe lower extremity pain that did not meet criteria for widespread pain was the next category . The reference category was no pain or mild pain in one site . The additional category of \" other pain \" was pain that did not fit into the other three groups . The occurrence of falls and fall-related injuries were assessed at each interview . RESULTS Of the 940 women who participated in at least one follow-up examination , 39 % fell in first year ; of the survivors , 36 % fell in Year 2 , and 39 % in Year 3 . After adjusting for several major risk factors for falls , women with widespread pain had an increased likelihood of falling during follow-up ( adjusted odds ratio ( AOR ) = 1.66 , 95 % confidence interval ( CI ) = 1.25 - 2.21 ) compared with those with no or mild pain in only one musculoskeletal site . Women who had other musculoskeletal pain but not widespread pain or lower extremity pain also had an increased risk of falls ( AOR = 1.36 , 95 % CI = 1.02 - 1.82 ) . Among women with musculoskeletal pain , risk for falls was lower in those who used daily analgesic medication . Risk for recurrent falls and self-reported fractures due to falls was also elevated in women with musculoskeletal pain , most consistently in women with widespread pain . CONCLUSIONS Musculoskeletal pain , particularly widespread pain , is a substantial risk factor for falls in older women with disabilities . These findings add an important dimension to our underst and ing of the multifactorial processes leading to falls in older persons", "OBJECTIVES Previous cross-sectional studies have shown a correlation between falls and fear of falling , but it is unclear which comes first . Our objectives were to determine the temporal relationship between falls and fear of falling , and to see whether these two outcomes share predictors . DESIGN A 20-month , population -based , prospect i ve , observational study . SETTING Salisbury , Maryl and . Each evaluation consisted of a home-administered question naire , followed by a 4- to 5-hour clinic evaluation . PARTICIPANTS The 2,212 participants in the Salisbury Eye Evaluation project who had baseline and 20-month follow-up clinic evaluations . At baseline , subjects were aged 65 to 84 and community dwelling and had a Mini-Mental State Examination score of 18 or higher . MEASUREMENTS Demographics , visual function , comorbidities , neuropsychiatric status , medication use , and physical performance-based measures were assessed . Stepwise logistic regression analyses were performed to evaluate independent predictors of falls and fear of falling at the follow-up evaluation , first predicting incident outcomes and then predicting fall or fear-of-falling status at 20 months with baseline falling and fear of falling as predictors . RESULTS Falls at baseline were an independent predictor of developing fear of falling 20 months later ( odds ratio ( OR ) = 1.75 ; P fear of falling at baseline was a predictor of falling at 20 months ( OR = 1.79 ; P Women with a history of stroke were at risk of falls and fear of falling at follow-up . In addition , Parkinson 's disease , comorbidity , and white race predicted falls , whereas General Health Question naire score , age , and taking four or more medications predicted fear of falling . CONCLUSION Individuals who develop one of these outcomes are at risk for developing the other , with a result ing spiraling risk of falls , fear of falling , and functional decline . Because falls and fear of falling share predictors , individuals who are at a high risk of developing these endpoints can be identified", "This large prospect i ve cohort study was undertaken to construct a fall-risk model for elderly . The emphasis of the study rests on easily measurable predictors for any falls and recurrent falls . The occurrence of falls among 1285 community-dwelling elderly aged 65 years and over was followed during 1 year by means of a \" fall calendar . \" Physical , cognitive , emotional and social functioning preceding the registration of falls were studied as potential predictors of fall-risk . Previous falls , visual impairment , urinary incontinence and use of benzodiazepines were the strongest predictors identified in the risk profile model for any falls ( area under the curve [ AUC ] = 0.65 ) , whereas previous falls , visual impairment , urinary incontinence and functional limitations proved to be the strongest predictors in the model for recurrent falls ( AUC = 0.71 ) . The probability of recurrent falls for subsequent scores of the screening test ranged from 4.7 % ( 95 % Confidence Interval [ CI ] : 4.0 - 5.4 % ) to 46.8 % ( 95 % CI : 43.0 - 50.6 % ) . Our study provides a fall-risk screening test based on four easily measurable predictors that can be used for fall-risk stratification in community-dwelling elderly", "Objective : To construct a risk model in order to identify elderly individuals at risk of frequent falling . Design : Prospect i ve community-based cohort study over 12 months . Setting : Baseline measures were performed at a local community centre . Subjects : Two hundred and sixty-three community-dwelling elderly people ( mean age 72 years ) . Measurements : A variety of variables were evaluated , including medical , psychological , sensory , physical and postural control measurements . Fall incidence was monitored retrospectively and during one-year follow-up . Results : Logistic regression analysis showed that polypharmacia was the most prominent medical fall predictor with an odds ratio ( OR ) of 1.29 ( P = 0.005 ) , poor visual acuity the best sensory predictor ( OR=0.84 ; P = 0.009 ) and general fear of falling the most crucial psychological predictor ( OR=3.25 ; P B=0.001 ) . Increased postural sway in near-t and em stance with eyes open was selected as the best balance predictor for falls ( OR=5.60 ; P = 0.010 ) , followed by delayed anteroposterior movement velocity during rhythmic weight shifts ( OR=0.42 ; P = 0.004 ) . The best physical predictor was a low score on the Physical Performance Test ( OR=4.16 ; P maximal h and grip strength ( OR=0.87 ; P timed chair-st and s ( OR=1.13 ; P falls , as a combination of the Physical Performance Test and maximal h and grip strength . Conclusion : This study confirms the multicausality of falls , since medical , psychological , sensory , postural control as well as physical variables provides a predictive value . The composed fall risk model was mainly physically oriented", "OBJECTIVES To examine the association between alcohol intake and problem drinking history and bone mineral density ( BMD ) , falls and fracture risk . DESIGN Cross-sectional and prospect i ve cohort study . SETTING Six U.S. clinical centers . PARTICIPANTS Five thous and nine hundred seventy-four men aged 65 and older . MEASUREMENTS Alcohol intake and problem drinking histories were ascertained at baseline . Follow-up time was 1 year for falls and a mean of 3.65 years for fractures . RESULTS Two thous and one hundred twenty-one participants ( 35.5 % ) reported limited alcohol intake ( or = 14 drinks/wk ) in the year before baseline . One thous and one men ( 16.8 % ) had ever had problem drinking . In multivariate models , as alcohol intake increased , so did hip and spine BMD ( P for trend nonspine or hip fractures . Men with light intake , but not moderate to heavy intake , had a lower risk of two or more incident falls ( light intake : relative risk ( RR ) = 0.77 , 95 % confidence interval ( CI ) = 0.65 - 0.92 ; moderate to heavy intake : RR = 0.83 , 95 % CI = 0.63 - 1.10 ) than abstainers . Men with problem drinking had higher femoral neck ( + 1.3 % ) and spine BMD ( + 1.4 % ) , and a higher risk of two or more falls ( RR = 1.59 ; 95 % CI = 1.30 - 1.94 ) than those without a history of problem drinking and similar total hip BMD and risk of fracture . CONCLUSION In older men , recent alcohol intake is associated with higher BMD . Alcohol intake and fracture risk is unclear . Light alcohol intake may decrease the risk of falling , but a history of problem drinking increased fall risk", "BACKGROUND Falls are a common occurrence in elderly persons , including relatively healthy , community-dwelling men and women . A significant percentage of falls result in soft-tissue injuries . Although some risk factors for falls have been identified , more research is needed on risk factors for injurious falls . In addition , there is little information from prospect i ve studies on the long-term consequences of falls other than injury . METHODS Risk factors and consequences of falls were analyzed in a 24-month prospect i ve study of 482 elderly ( mean age 74 + /- 6.7 years ) men and women living independently.in the community . Falls and injurious falls were ascertained by telephone and by a bimonthly postcard follow-up . Predictor variables were obtained from a baseline assessment and follow-up question naire . Outcomes were defined as rates of falls and injurious falls , circumstances surrounding the fall , and the long-term correlates of falls . RESULTS Sixty-one percent of the participants ( 53.7 % of men and 65.7 % of women ) reported one or more falls during the 2-year follow-up . The crude rates of injurious falls were 11.17 per 1000 person-months in women and 7.23 per 1000 person-months in men . Age , history of fracture , low physical health , and low or high mobility level were risk factors for injurious falls in both sexes . The inability to balance unsupported on one leg was associated with injurious falls in women ( rate ratio [ RR ] = 3.0 ; 95 % confidence interval 1.9 - 4.7 ) . Self-reported cognitive , physical health , and mobility impairments were greater in female fallers compared to the nonfallers . CONCLUSIONS Falls and injurious falls without fracture are frequent events for healthy elderly people and may be associated with morbid changes in cognitive status , physical health , and mobility", "Objective : To explore associations between physical activity and the risk of falls and fractured bones in community-dwelling older women . Design , setting and participants : A prospect i ve observational survey with three and six-year follow-ups . The sample included 8188 healthy , community-dwelling women , aged 70–75 years in 1996 , who completed surveys as participants in the Australian Longitudinal Study on Women ’s Health . Women who reported a recent serious injury from falling were excluded . Outcomes were reports of a fall to the ground , injury from a fall , and a fractured bone in 1999 and 2002 . The main predictor variable was physical activity level in 1996 , categorised on the basis of weekly frequency as none/very low , low , moderate , high and very high . Covariates were demographic and health-related variables . Logistic regression models were computed separately for each outcome in 1999 and 2002 . Main results : In multivariable models , very high physical activity was associated with a decreased risk of reporting a fall in 1999 ( odds ratio ( OR ) 0.67 ; 95 % CI 0.47 to 0.95 ) and in 2002 ( OR 0.64 ; 95 % CI 0.43 to 0.96 ) . High/very high physical activity was associated with a decreased risk of a fractured bone in 2002 ( OR 0.53 ; 95 % CI 0.34 to 0.83 ) . No significant association was found between physical activity and injury from a fall . Conclusions : The results suggest that at least daily moderate to vigorous-intensity physical activity is required for the primary prevention of falls to the ground and fractured bones in women aged 70–75 years", "OBJECTIVES To determine whether current use of central nervous system (CNS)-active medications , including benzodiazepines , antidepressants , anticonvulsants , and narcotics , increases the risk for subsequent falls . DESIGN Prospect i ve cohort study . SETTING Four clinical centers in Baltimore , Maryl and ; Portl and , Oregon ; Minneapolis , Minnesota ; and the Monongahela Valley , Pennsylvania . PARTICIPANTS Eight thous and one hundred twenty-seven women aged 65 and older participating in the fourth examination of the Study of Osteoporotic Fractures between 1992 and 1994 . MEASUREMENTS Current use of CNS-active medications was assessed with an interviewer-administered question naire with verification of use from medication containers . A computerized dictionary was used to categorize type of medication from product br and and generic names . Incident falls were reported every 4 months for 1 year after the fourth examination . RESULTS During an average follow-up of 12 months , 2,241 women ( 28 % ) reported falling at least once , including 917 women ( 11 % ) who experienced two or more ( frequent ) falls . Compared with nonusers , women using benzodiazepines ( multivariate odds ratio ( MOR ) = 1.51 , 95 % confidence interval ( CI ) = 1.14 - 2.01 ) , those taking antidepressants ( MOR = 1.54 , 95 % CI = 1.14 - 2.07 ) , and those using anticonvulsants ( MOR = 2.56 , 95 % CI = 1.49 - 4.41 ) were at increased risk of experiencing frequent falls during the subsequent year . We found no evidence of an independent association between narcotic use and falls ( MOR = 0.99 for frequent falling , 95 % CI = 0.68 - 1.43 ) . Among benzodiazepine users , both women using short-acting benzodiazepines ( MOR = 1.42 , 95 % CI = 0.98 - 2.04 ) and those using long-acting benzodiazepines ( MOR = 1.56 , 95 % CI = 1.00 - 2.43 ) appeared to be at greater risk of frequent falls than nonusers , although the CIs overlapped 1.0 . We found no evidence to suggest that women using selective serotonin-reuptake inhibitors ( MOR = 3.45 , 95 % CI = 1.89 - 6.30 ) had a lower risk of frequent falls than those using tricyclic antidepressants ( MOR 1.28 , 95 % CI = 0.90 - 1.84 ) . CONCLUSIONS Community-dwelling older women taking CNS-active medications , including those taking benzodiazepines , antidepressants , and anticonvulsants , are at increased risk of frequent falls . Minimizing use of these CNS-active medications may decrease risk of future falls . Our results suggest that fall risk in women taking benzodiazepines is at best marginally decreased by use of short-acting preparations . Similarly , our findings indicate that preferential use of selective serotonin-reuptake inhibitors is unlikely to reduce fall risk in older women taking antidepressants", "Objective . The aim of this prospect i ve study was to examine risk factors of falling in a very old home-dwelling population . Design . A prospect i ve study of home-dwelling elderly people . Methods . Baseline data were collected by home-nursing staff through postal question naires and clinical tests . Data on falls were recorded in telephone interviews every other month during a follow-up of 11 months constituting 494 person years ( PY ) . Negative binomial modeling was used to assess fall risk . Setting . General community . Subjects . A population sample of home-dwelling subjects aged 85 years or older ( n = 555 ) . Main outcome measures . Fall rate and risk factors of falls . Results . Altogether 512 falls occurred in 273 ( 49 % ) subjects , incidence rate 1.03/PY . According to a multivariate model , history of recurrent falling , trouble with vision when moving , use of antipsychotic drug , and feelings of anxiety , nervousness , or fear were independent risk factors for subsequent falls . Conclusion . Appropriate care of poor vision and feelings of anxiety , nervousness , or fear , and avoidance of use of antipsychotic drugs might be useful in the prevention of falls among the most elderly home-dwellers ", "OBJECTIVE To define the risk factors for recurrent falls in the home-dwelling elderly . DESIGN A prospect i ve population -based study covering two years . SETTING Five rural municipalities around the city Oulu , northern Finl and . PARTICIPANTS All home-dwelling elderly persons ( N = 1,016 ) aged 70 years or older living in the municipalities . OUTCOME MEASURES The risk factors of recurrent falling by variables related to social status , life changes , housing conditions , health , functional abilities and life style , using cross-tabulations and multivariate analyses . RESULTS The recurrent fallers ( at least two falls within 365 days after the examination day ) consisted of 17 men ( 6 % of the men ) and 71 women ( 14 % ) . Logistic regression analyses showed female sex , urinary urgency , frequent fear of falling , dizziness , a poor pulse rate rise 30 seconds after st and ing up and falling during the previous year to be risk factors for recurrent falls . After the variable representing previous falls had been removed from the analysis , urinary incontinence and a change in housing conditions during the past two years emerged and urinary urgency dropped out of the model . CONCLUSIONS Women particularly are a target group for the prevention of falls among the elderly . Urinary urgency and urinary incontinence , fear of falling , dizziness and changes in the housing conditions should be inquired about to identify the elderly at risk for falling and to take preventive interventions . In addition to testing blood pressure changes after st and ing up , the changes in pulse rate should be determined to identify and treat elderly people who have orthostatic conditions", "OBJECTIVES To examine the association between Parkinson 's disease ( PD ) and bone mineral density ( BMD ) and risk of falls . DESIGN Cross-sectional and prospect i ve cohort study . SETTING Six U.S. clinical centers . PARTICIPANTS Five thous and nine hundred ninety-five community-dwelling , ambulatory men aged 65 and older . MEASUREMENTS History of physician-diagnosed PD was ascertained from participant self-report . BMD was measured at the hip and spine using dual energy x-ray absorptiometry ( DEXA ) and quantitative computed tomography ( QCT ) . Incident falls were ascertained for 1 year using mailed queries . RESULTS Fifty-two participants ( 0.9 % ) reported a history of PD . In multivariate models , PD was associated with significantly lower BMD at the spine ( -4.9 % , P=.04 ) and total hip ( -5.3 % , P=.007 ) using DEXA and at the spine ( -6.7 % , P=.05 ) and total hip ( -8.2 % , P=.03 ) using QCT . PD was associated with a nearly three times greater age-adjusted risk of multiple future falls ( odds ratio (OR)=2.91 , 95 % confidence interval (CI)=1.55 - 5.46 ) . Further adjustment for history of multiple falls in the year before baseline attenuated this risk , but it remained significant ( OR=2.30 , 95 % CI=1.15 - 4.59 ) . CONCLUSION In this cohort of older men , PD was associated with lower BMD at the hip and spine , measured using areal and volumetric BMD , as well as increased falls . Clinicians should consider screening older men with PD for osteoporosis", "Background and aims : In the elderly , balance and walking impairments are assumed to play an important role in causing falls . We have assessed prospect ively the predictive ability of health , function and balance variables regarding falls and their location . Methods : Falls which occurred during one year in a r and om sample of 307 women aged 75 years and over ( mean 80.8 years , response rate 74.5 % ) living in the community were recorded and related to baseline registration s of health , medication and tests of walking and balance . Results : In all , 155 women ( 50.5 % ) reported 308 falls . Outdoor falls were significantly more frequent than indoor falls ( 57.5 vs 42.5 % ) . The variables having had a fall before the start of the study , osteoporosis , hypertension , feeling depressed , unable to climb 40 cm high steps and walking slowly , all independently predicted a higher number of falls overall . Regarding fall location , having experienced a fall before study start was associated with more falls indoors as well as outdoors . Vision impairment , symptoms of depression , a faster comfortable walking speed , and being able to cope with higher steps were all independent predictors of more outdoor falls also after adjustment for outdoor exposure . A slower comfortable walking speed , a higher amplitude of the center of pressure movements in the frontal plane , a poorer score on the Timed Up & Go test , multi-morbidity , poor cognition and hypertension were independent risk factors for indoor falls . Neither number of drugs used nor any specific medication appeared as independent risk factors for falls in this study . Conclusions : The findings of this study suggest that risk factors for indoor and outdoor falls are different . Location of fall may be an important confounder in studies of predictors of falls in the elderly which should encompass this type of information", "To study risk factors for falling , we conducted a one-year prospect i ve investigation , using a sample of 336 persons at least 75 years of age who were living in the community . All subjects underwent detailed clinical evaluation , including st and ardized measures of mental status , strength , reflexes , balance , and gait ; in addition , we inspected their homes for environmental hazards . Falls and their circumstances were identified during bimonthly telephone calls . During one year of follow-up , 108 subjects ( 32 percent ) fell at least once ; 24 percent of those who fell had serious injuries and 6 percent had fractures . Predisposing factors for falls were identified in linear-logistic models . The adjusted odds ratio for sedative use was 28.3 ; for cognitive impairment , 5.0 ; for disability of the lower extremities , 3.8 ; for palmomental reflex , 3.0 ; for abnormalities of balance and gait , 1.9 ; and for foot problems , 1.8 ; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables . The risk of falling increased linearly with the number of risk factors , from 8 percent with none to 78 percent with four or more risk factors ( P less than 0.0001 ) . About 10 percent of the falls occurred during acute illness , 5 percent during hazardous activity , and 44 percent in the presence of environmental hazards . We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling", "Introduction The purpose of this study was to examine the relationships of vitamin D supplementation and serum concentrations of vitamin D metabolites and parathyroid hormone ( PTH ) with neuromuscular function and falls in older community-dwelling women . Methods We examined these relationships using a 4-year prospect i ve multi-center study among 9,526 community-dwelling women enrolled in the Study of Osteoporotic Fractures ( median age : 70 years ; interquartile range : 67–75 ) and a subset of 389 women ( 97 % ) out of 400 who were r and omly selected from the entire cohort for serum measures . Measurements included : vitamin D supplementation , serum 25-hydroxyvitamin D3 [ 25(OH)D3 ] , serum 1,25-dihydroxyvitamin D3 [ 1,25(OH ) 2D3 ] , and serum intact parathyroid hormone ( iPTH ) ; grip and quadriceps strength , chair-st and time , walking speed , reaction time , and balance-walk time ( including changes in grip strength , chair-st and time , walking speed and balance-walk time over approximately 3.7 years ) ; and incident fall rates ( number of falls/woman-years ) . Results In 9,526 women , vitamin D supplementation was not associated with any measures of neuromuscular function , change in neuromuscular function , or fall rates ( p>0.01 for all ) . In a subgroup of 389 women , there was a trend of higher 25(OH)D3 concentration with slightly weaker grip strength ( p=0.007 ) , and women in the fourth quartile of 1,25(OH)2D3 had a faster chair-st and time ( p=0.017 ) than women in the first quartile ; still , in general , concentrations of 25(OH)D3 , 1,25(OH)2D3 , and iPTH were not associated with either neuromuscular function or changes in neuromuscular function ( p>0.05 for all ) . However , higher 1,25(OH)2D3 concentration was associated with lower fall rates ( p=0.039 ) . Conclusions Higher 1,25(OH)2D3 concentration is associated with a lower fall risk in older community-dwelling women , but vitamin D supplementation , and 25(OH)D3 and iPTH concentrations are not associated with either neuromuscular function or falls", "The object of this article was to determine the predictive value of risk factors for recurrent falls and the construction of a fall risk model as a contribution to a mobility assessment for the identification of community-dwelling elderly at risk for recurrent falling in general practice . The design was a prospect i ve cohort study ( n = 311 ) . There were four primary health care centers . A sample stratified on previous falls , age , and gender of community-dwelling elderly persons aged 70 years or over ( n = 311 ) was taken from the respondents to a mail question naire ( n = 1660 ) . They were visited at home to assess physical and mental health , balance and gait , mobility and strength . A 36-week follow-up with telephone calls every 6 weeks was conducted . Falls and fall injuries were measured . During follow-up 197 falls were reported by 33 % of the participants : one fall by 17 % and two or more falls by 16 % . Injury due to a fall was reported by 45 % of the fallers : 2 % hip fractures , 4 % other fractures , and 39 % minor injuries . A fall risk model for the prediction of recurrent falls with an area under the curve ( AUC ) of 0.79 , based on logistic regression analysis , showed that the main determinants for recurrent falls were : an abnormal postural sway ( OR 3.9 ; 95 % Cl 1.3 - 12.1 ) , two or more falls in the previous year ( OR 3.1 ; 95 % Cl 1.5 - 6.7 ) , low scores for h and grip strength ( OR 3.1 ; 95 % Cl 1.5 - 6.6 ) , and a depressive state of mind ( OR 2.2 ; 95 % CI 1.1 - 4.5 ) . To facilitate the use of the model for clinical practice , the model was converted to a \" desk model \" with three risk categories : low risk ( 0 - 1 predictor ) , moderate risk ( two predictors ) , and high risk ( > or =3 predictors ) . A fall risk model converted to a \" desk model , \" consisting of the predictors postural sway , fall history , h and dynamometry , and depression , provides added value in the identification of community-dwelling elderly at risk for recurrent falling and facilitates the prediction of recurrent falls", "OBJECTIVES To determine whether genetic influences account for individual differences in susceptibility to falls in older women . DESIGN Prospect i ve twin cohort study . SETTING Research laboratory and residential environment . PARTICIPANTS Ninety-nine monozygotic ( MZ ) and 114 dizygotic ( DZ ) female twin pairs aged 63 to 76 from the Finnish Twin Cohort study . MEASUREMENTS The participants recorded their falls on a calendar for an average+/-st and ard deviation of 344+/-41 days . Reported falls were verified via telephone interview , and circumstances , causes , and consequences of the fall were asked about . RESULTS The total number of falls was 434 , of which 188 were injurious ; 91 participants had two or more falls . Casewise concordance was 0.61 ( 95 % confidence interval (CI)=0.49 - 0.72 ) for MZ twins and 0.49 ( 95 % CI=0.37 - 0.62 ) for DZ twins for at least one fall , 0.38 ( 95 % CI=0.23 - 0.53 ) for MZ and 0.33 ( 95 % CI=0.17 - 0.50 ) for DZ twins for at least one injurious fall , and 0.43 ( 95 % CI=0.26 - 0.60 ) for MZ and 0.36 ( 95 % CI=0.17 - 0.55 ) for DZ twins for recurrent falls . On average , the proportion of familial influences accounting for the individual differences in susceptibility to at least one fall was 30 % and to recurrent falls was 40 % ; nongenetic familial and nonfamilial factors alone accounted for susceptibility to at least one injurious fall . CONCLUSION In community-dwelling older women , familial factors underlie the risk of falling but not the risk of injurious falls", "To determine how accurately elderly subjects recall recent falls , we studied 304 ambulatory men and women over the age of 60 years who completed a 12-month prospect i ve study of risk factors for falling . We developed a system of weekly follow-up and home visits to record and confirm all falls . During the study , 179 participants suffered at least one fall that was confirmed by home visit . At the end of the study , all subjects were interviewed by telephone about whether they had suffered a fall during the preceding 3 , 6 , or 12 months . Depending on the time period of recall , 13 % to 32 % of those with confirmed falls did not recall falling during the specific period of time . Recall was better for the preceding 12 months than for 3 or 6 months . There were only weak correlations ( r = 0.28 to 0.59 ) between the number of falls that were documented and the number that the subjects recalled during each of these periods . Those with lower scores on the Mini-Mental State Examination were more likely to forget falls . We conclude that elderly subjects often do not recall falls that occurred during specific periods of time over the preceding 3 to 12 months . Research ers and clinicians should consider using methods besides long-term recall for ascertaining and counting falls over specific periods of time", "OBJECTIVES This study was undertaken to determine whether vigorous and frail older people who identify environmental hazards in their homes have an increased risk for falls . METHODS A 1-year prospect i ve study was conducted among 266 female and 59 male community-dwelling volunteers aged 60 to 93 years who had fallen at least once during the previous year . Composite measures of home safety and of frailty were derived using principal components analysis . Participants were divided into vigorous and frail groups , and associations between baseline home safety measures and falls at home over the follow-up year were compared between the two groups . RESULTS Frail individuals were more than twice as likely as vigorous individuals to fall during follow-up ( rate ratio [ RR ] = 2.24 ; 95 % confidence interval [ CI ] = 1.54 , 3.27 ) . In the study group as a whole , falls were not strongly associated with the presence of home hazards . However , when compared with vigorous older persons living with fewer home hazards , vigorous older persons living with more home hazards were more likely to fall . The increased risk for falls among vigorous elderly was limited to falls where home hazards were present . By contrast , living with more home hazards was not associated with increased likelihood of falls among frail older persons . CONCLUSIONS While frail older persons experience higher overall fall rates , vigorous older persons should not be overlooked in fall prevention projects", "OBJECTIVES To compare the value of dual tasking in predicting falling in the general population of oldest old with that of easy-to-administer single tasks . DESIGN Prospect i ve population -based follow-up study . SETTING Municipality of Leiden , the Netherl and s. PARTICIPANTS Representative cohort of 380 individuals , all aged 85 at baseline . MEASUREMENTS During enrollment , walking time over a 12-meter distance was measured , as well as the verbal fluency to recite names of animals or professions during a 30-second period . In the dual task , performance was assessed when participants combined walking with reciting names . Incidence of falls and fractures was assessed by interviewing participants and checking their medical histories . RESULTS After 1 year of follow-up , 42 % of the participants reported one or more falls , and 4 % suffered a fracture . Total walking time , number of steps , and verbal fluency were all strongly related to incident falls ( P for trend for all dual-task performance was not a better predictor for incident falls than single-task performance . CONCLUSION The dual-task test in this study had no predictive value above that of a single-task test to predict falling . Dual tasks with more-sensitive measures of impaired dual-task execution might have better test characteristics . In this study , history of falls and performance on an easy-to-administer single walking task identified old persons at higher risk for falling who could benefit from fall preventive strategies", "OBJECTIVE Fall risk assessment is important because the consequences , such as a fracture , may be devastating . The objective of this study was to find the test or tests that best predicted falls in a population -based sample of elderly women . STUDY DESIGN AND SETTING The fall-predictive ability of a question naire , a subjective estimate of biologic age and objective functional tests ( gait , balance [ Romberg and sway test ] , thigh muscle strength , and visual acuity ) were compared in 984 r and omly selected women , all 75 years of age . RESULTS A recalled fall was the most important predictor for future falls . Only recalled falls and intake of psycho-active drugs independently predicted future falls . Women with at least five of the most important fall predictors ( previous falls , conditions affecting the balance , tendency to fall , intake of psychoactive medication , inability to st and on one leg , high biologic age ) had an odds ratio of 11.27 ( 95 % confidence interval 4.61 - 27.60 ) for a fall ( sensitivity 70 % , specificity 79 % ) . CONCLUSION The more time-consuming objective functional tests were of limited importance for fall prediction . A simple clinical history , the inability to st and on one leg , and a subjective estimate of biologic age were more important as part of the fall risk assessment", "OBJECTIVE Scant attention has been paid to the risk factors for recurrent falls among the home-dwelling elderly , although there are remarkable age and sex differences according to whether or not the falls recur . In this report we describe and analyse the risk factors for recurrent falls by selected clinical variables and the history of falling during the previous year . DESIGN A community-based prospect i ve study covering two years . SETTING All home-dwelling persons ( N = 1016 ) aged 70 years or older living in five municipalities in northern Finl and . OUTCOME MEASURES The risk factors of recurrent falling by selected clinical variables using cross-tabulations and multivariate analyses . RESULTS Previous falls , peripheral neuropathy , use of psychotropic medication and slow walking speed were independent risk factors for recurrent falling . The risk of recurrent falling increased with an increasing number of previous falls . CONCLUSIONS Early preventive measures should be taken among the elderly persons who are prone to falling . In order to reduce the risk of recurrent falls among the elderly , the attending physician should take a critical view of the use of psychotropic medications , and attempts should be made to treat conditions underlying peripheral neuropathies and abnormal gait", "BACKGROUND Falls frequently occur in the elderly and are a major cause of morbidity and mortality . OBJECTIVE The objective of the study was to prospect ively investigate the association between serum 25-hydroxyvitamin D [ 25(OH)D ] levels and risk of recurrent falling in older men and women . DESIGN This was a prospect i ve cohort study . SETTING An age- and sex-stratified r and om sample of the Dutch older population was determined . SUBJECTS Subjects included 1231 men and women ( aged 65 yr and older ) participating in the Longitudinal Aging Study Amsterdam . MEASUREMENTS Baseline serum 25(OH)D was determined by a competitive protein binding assay . During 1 yr , falls were prospect ively recorded by means of a fall calendar . RESULTS Low 25(OH)D ( increased risk of falling . After adjustment for age , sex , education level , region , season , physical activity , smoking , and alcohol intake , the odds ratios ( 95 % confidence interval ) were 1.78 ( 1.06 - 2.99 ) for subjects who experienced two falls or more as compared with those who did not fall or fell once and 2.23 ( 1.17 - 4.25 ) for subjects who fell three or more times as compared with those who fell two times or less . There was a statistically significant effect modification by age , and stratified analyses ( or = 75 yr ) showed that the associations were particularly strong in the younger age group ; the odds ratios ( 95 % confidence interval ) were 5.21 ( 2.03 - 13.40 ) for two falls or more and 4.96 ( 1.52 - 16.23 ) for three falls or more . CONCLUSIONS Poor vitamin D status is independently associated with an increased risk of falling in the elderly , particularly in those aged 65 - 75 yr", "Background : While central nervous system ( CNS ) active medications such as psychotropics and narcotic analgesics have been implicated in contributing to falls in older adults , the combined effect of multiple CNS-active medications has not been investigated . The purpose of this study was to examine the influence , in community-dwelling elderly , of ( 1 ) taking multiple CNS-active medications on fall liability and ( 2 ) individual classes of CNS-active medications ( using discrete drug classification ) on the risk of falls after controlling for important confounders – age , mobility , cognition and depression . Methods : 305 community-dwelling male veterans ( age : 70–104 ) were screened at study entry for mobility , cognition and depression . CNS-active medications were categorized as benzodiazepines , other sedative-hypnotics , neuroleptics , tricyclic antidepressants , and opioid analgesics . Subjects were prospect ively followed for 6 months to monitor falls ; at the end of this time period , subjects were classified as fallers ( at least one fall ) or nonfallers . The relationship between CNS-active drug use and falls was examined using multivariable analyses . Results : The risk of falls was significantly greater in CNS-active medication users as compared with nonusers . Adjusted odds ratio for one CNS-active drug was 1.54 ( 95 % confidence interval 1.07–2.22 ) and for two or more agents 2.37 ( 95 % confidence interval 1.14–4.94 ) . Conclusions : In community-dwelling elderly , the use of multiple CNS-active medications is associated with enhanced falls liability , over and above the use of one CNS-active drug alone . This apparent dose-response relationship provides support for causality" ]	411846fe-06ff-11f0-808a-c43d1ab1c353
Background Sleep undergoes changes from birth to adulthood , while sleep disorders are associated with various cognitive deficiencies in childhood . In parallel , prematurity is known to predispose to poor neurodevelopmental outcomes . Our aim is to provide literature data about factors influencing sleep in the premature infants and sleep outcomes in this population . Methods A systematic review was conducted using a variety of health-related data bases . Original research papers were considered and no year-of-publication restriction was placed . Results In total , 22 articles fulfilled our selection criteria . Available studies present remarkable heterogeneity in terms of method ological design . Compared to full term , premature infants exhibit significant differences in sleep structure , which mainly include differences in electroencephalographic spectral values , in total sleep time and in arousal threshold . Furthermore , prematurity seems to be a risk factor of sleep breathing disorders in childhood and adolescence . Data about the effect of methylxanthines and the environment of neonatal intensive care unit is controversial . With regard to the impact of prematurity-related sleep disorders on future neurodevelopment , available research papers are generally few . Conclusions The alterations in sleep patterns are an outcome of prematurity ( immaturity of nervous system ) as well as of postnatal factors and comorbidities . Sleep problems in this population of infants seems to be a missing piece of the puzzle of impaired neurodevelopment . Future studies should focus on interventions to improve sleep hygiene and limit neurodevelopmental problems	[ "RATIONALE Apnea of prematurity is a common condition that is usually treated with caffeine , an adenosine receptor blocker that has powerful influences on the central nervous system . However , little is known about the long-term effects of caffeine on sleep in the developing brain . OBJECTIVES We hypothesized that neonatal caffeine use result ed in long-term abnormalities in sleep architecture and breathing during sleep . METHODS A total of 201 ex-preterm children aged 5 - 12 years who participated as neonates in a double-blind , r and omized , controlled clinical trial of caffeine versus placebo underwent actigraphy , polysomnography , and parental sleep question naires . Co primary outcomes were total sleep time on actigraphy and apnea-hypopnea index on polysomnography . MEASUREMENTS AND MAIN RESULTS There were no significant differences in primary outcomes between the caffeine group and the placebo ( adjusted mean difference of -6.7 [ 95 % confidence interval ( CI ) = -15.3 to 2.0 min ] ; P = 0.13 for actigraphic total sleep time ; and adjusted rate ratio [ caffeine/placebo ] for apnea-hypopnea index of 0.89 [ 95 % CI = 0.55 - 1.43 ] ; P = 0.63 ) . Polysomnographic total recording time and total sleep time were longer in the caffeine group , but there was no difference in sleep efficiency between groups . The percentage of children with obstructive sleep apnea ( 8.2 % of caffeine group versus 11.0 % of placebo ; P = 0.22 ) or elevated periodic limb movements of sleep ( 17.5 % in caffeine group versus 11 % in placebo group ) was high , but did not differ significantly between groups . CONCLUSIONS Therapeutic neonatal caffeine administration has no long-term effects on sleep duration or sleep apnea during childhood . Ex-preterm infants , regardless of caffeine status , are at risk for obstructive sleep apnea and periodic limb movements in later childhood", "OBJECTIVE : To examine whether cycled lighting ( CL ) conditions during neonatal care in very preterm infants ( decrease crying and fussing behavior , improve the consolidation of sleep , and influence activity behavior at 5 and 11 weeks ’ postterm corrected age ( CA ) compared with preterm infants cared for in dim lighting ( DL ) conditions . METHODS : Thirty-seven preterm infants were r and omly assigned to CL ( 7 am–7 pm lights on , 7 pm–7 am lights off [ n = 17 ; mean GA : 30.6 ± 0.95 weeks ; 9 girls ] ) or DL ( lights off whenever the child is asleep [ n = 20 ; GA : 29.5 ± 2.1 weeks ; 8 girls ] ) conditions . Sleeping , crying , and activity behavior was recorded by using parental diaries and actigraphy at 5 and 11 weeks ’ CA . RESULTS : A significant reduction of fussing ( 59.4 minutes/24 hours [ ±25.8 minutes ] ) and crying ( 31.2 minutes/24 hours [ ±14.4 minutes ] ) behavior and a trend to higher motor activity during daytime was found in CL-exposed infants at 5 and 11 weeks ’ CA compared with infants cared for in DL conditions . No significant difference between groups was observed for sleep behavior at 5 and 11 weeks ’ CA . Infants in CL conditions showed a trend to improved daily weight gain ( average : 3.6 g/d ) during neonatal care compared with DL conditions . CONCLUSIONS : CL conditions in neonatal care have beneficial effects on infant ’s fussing and crying behavior and growth in the first weeks of life . This study supports the introduction of CL care in clinical neonatal practice", "OBJECTIVES To evaluate the extent to which sleep-disordered breathing ( SDB ) varies with putative demographic and medical risk factors and to estimate the prevalence of undiagnosed SDB . STUDY DESIGN Prospect i ve , cross-sectional study in a population -based cohort of 850 children ( 41 % black , 46 % preterm ) , 8 to 11 years of age . Participants ' caretakers completed question naires about health and sleep . Children underwent overnight in-home cardiorespiratory recordings of airflow , respiratory effort , oximetry , and electrocardiography . SDB was identified by respiratory disturbance indices commonly applied in clinical practice . Risk factors were estimated by logistic regression . Prevalence was derived from cohort-specific estimates with birth weights from US live births data . RESULTS Using the most inclusive definition , SDB was detected in 40 ( 4.7 % ) participants , with prevalence varying widely across population subsets . Depending on the definition used , SDB was 4 to 6 times more likely in black children compared with white children and almost 3 to 5 times more likely in former preterm compared with term children . The estimated population prevalence of SDB was 2.2 % ( 95 % CI , 1.2 % , 3.2 % ) . CONCLUSIONS SDB is a relatively common condition in 8- to 11-year-old children . Potentially vulnerable subgroups , black children , and former preterm infants , are at increased risk", "This prospect i ve observational study evaluated the behavioural responses of very preterm infants to spontaneous light variations", "BACKGROUND . Sleep is important to brain organization , but few strategies to promote sleep among premature infants have been tested . Behaviorally based measures of sleep have shown increased quiet sleep ( QS ) and decreased active sleep ( AS ) during skin-to-skin contact ( SSC ) with the mother , but these results have not been confirmed with objective electroencephalographic/polysomnographic measures of sleep organization . Important differences exist between behavioral and electroencephalographic/polysomnographic definitions of sleep state . METHODS . Data for the first 28 relatively healthy , preterm subjects of an ongoing r and omized trial of one 2- to 3-hour session of SSC or incubator care between feedings are reported here . Infants were positioned prone , inclined , and nested in an incubator during the 2- to 3-hour pretest period , were fed , and then went into the test period of SSC or incubator care . Infants were left largely undisturbed throughout testing . A mixed-model regression analysis compared the test-pretest differences in outcome measures within and between groups . RESULTS . Results showed that arousals were significantly lower in the SSC group , compared with the control group , for the entire study period and for test-pretest matched segments of QS and AS . Rapid eye movement was significantly lower for the SSC group for the study period and AS segments . Indeterminate sleep was significantly lower for the SSC group when confounding environmental variables were included in the regression analysis . When 4 subjects who experienced excessive ambient light levels during SSC were removed from analysis , QS increased during SSC . CONCLUSIONS . The patterns demonstrated by the SSC group are analogous to more-mature sleep organization . SSC may be used as an intervention to improve sleep organization in this population of preterm infants", "OBJECTIVES /HYPOTHESIS To report on the prevalence of premature ( PM ) birth in a consecutive series of children treated for snoring and sleep-disordered breathing ( S/SDB ) , the parameters specific to their management and variables predictive of disease severity . STUDY DESIGN A retrospective study was undertaken at a tertiary pediatric hospital . METHODS Children with history of PM and presenting with S/SDB were identified from a prospect ively kept surgical data base . We set out to determine the prevalence of PM among the patients presenting with S/SDB who required airway evaluations and surgery . Pulse oximetry is overnight recordable oxygen saturation and heart rate tracing that provides information about hypoxemia during sleep . This was performed on all children preoperatively . The pulse oximetry findings were used to plan for perioperative monitoring and care . A multivariable analysis was used to identify factors predictive of abnormal pulse oximetry studies . We evaluated the associated diagnoses , surgical procedures required , and response to treatment in these selected children . RESULTS Fifty-seven out of 1,038 patients were PM ( 33 males ; mean age , 62.09 ± 34.91 months ; range , 4 - 190 months ) . The mean gestational age was 30.3 ± 4.0 weeks . The prevalence rate of PM among patients treated surgically for SDB is 5.5 % ( 95 % CI 5.2 - 5.8 ) at our center . Comorbid pulmonary and gastrointestinal disorders were encountered on 23 ( 40 % ) and 17 ( 29.8 % ) occasions , respectively , and were the most commonly encountered comorbid diagnostic categories . Large airway abnormalities were encountered in 11 ( 19.3 % ) children , and the most common were subglottic stenosis ( four ) and laryngeal paralysis ( four ) . Comorbid respiratory disease was negatively predictive of abnormal pulse oximetry ( coefficient -0.35 , P Postoperative respiratory outcomes correlated with abnormal pulse oximetry ( coefficient 0.3 ; P children with PM presenting to pediatric otolaryngology require a comprehensive evaluation for S/SDB . A significant proportion of children with S/SDB and a history of PM frequently had pulmonary and gastrointestinal comorbidities in our cohort . One-half required admission postoperatively , and these were predictable based on preoperative pulse oximetry . Respiratory comorbidity was negatively predictive of severity of SDB . Inversely , children with untreated pulmonary comorbidities are more likely to have postoperative complications ", "Background : In neonatal intensive care unit ( NICU ) , neonatal sleep is disrupted due to different factors . Due to the critical role of sleep in premature infants′ brain development , this study aim ed to investigate the effect of nesting and swaddling on the sleep duration of premature infants hospitalized in NICUs . Material s and Methods : In a crossover clinical trial , 42 preterm infants who met the inclusion criteria were enrolled . They were r and omly assigned to two groups of nest-swaddle and swaddle-nest . Sleep status was evaluated by observation and use of Prechtl′s criteria . Then , duration s of total sleep time ( TST ) and quiet sleep time ( QST ) were recorded . Data were analyzed using repeated measure analysis of variance ( ANOVA ) . Results : Mean values of TST and QST during nesting and also swaddling periods were significantly higher than in the control period in both groups ( P ) . Mean values of TST and QST in the swaddling period were higher than in the nesting period in both groups , However , these differences were not significant ( P = 0.245 ) . Conclusions : Both swaddling and nesting could significantly increase the duration of TST and QST , compared to the control . There were no significant differences between the effects of these interventions on TST and QST . Therefore , using any of these methods is suggested to improve infants′ quality of sleep in NICU , with respect to the ward policies", "STUDY OBJECTIVES The obstructive sleep apnea syndrome ( OSAS ) is more prevalent in ex-preterm children compared to the general pediatric population . However , it is unknown whether OSAS in ex-preterm children is associated with specific perinatal risk factors . This multicenter cohort study aim ed to determine perinatal factors associated with OSAS at school age . METHODS 197 ex-preterm ( 500 - 1,250 g ) children aged 5 - 12 y who participated as neonates in a double-blind , r and omized clinical trial of caffeine versus placebo ( Caffeine for Apnea of Prematurity ) underwent comprehensive ambulatory polysomnography . A negative binomial regression model was used to identify perinatal risk factors associated with OSAS . RESULTS 19 children had OSAS ( 9.6 % ) . Chorioamnionitis and multiple gestation were positively associated with OSAS with P values of 0.014 and 0.03 , respectively . Maternal white race ( P = 0.047 ) and maternal age ( P = 0.002 ) were negatively associated with OSAS . Other risk factors , such as birth weight , Apgar score at 5 min , antenatal corticosteroids , delivery route , and sex were not significant . CONCLUSIONS OSAS is very frequent , and is associated with chorioamnionitis and multiple gestation in ex-preterm children . Those born to older white mothers appear to be protected . We speculate that the former may be due to systemic inflammation and the latter to a higher socio-economic status . COMMENTARY A commentary on this article appears in this issue on page 721", "OBJECTIVE . Prematurely born compared with term born infants are at increased risk of sudden infant death syndrome , particularly if slept prone . The purpose of this work was to test the hypothesis that preterm infants with or without bronchopulmonary dysplasia being prepared for neonatal unit discharge would sleep longer and have less arousals and more central apneas in the prone position . METHODS . This was a prospect i ve observational study in a tertiary NICU . Twenty-four infants ( 14 with bronchopulmonary dysplasia ) with a median gestational age of 27 weeks were studied at a median postconceptional age of 37 weeks . Video polysomnographic recordings of 2-channel electroencephalogram , 2-channel electro-oculogram , nasal airflow , chest and abdominal wall movements , limb movements , electrocardiogram , and oxygen saturation were made in the supine and prone positions , each position maintained for 3 hours . The duration of sleep , sleep efficiency ( total sleep time/total recording time ) , and number and type of apneas , arousals , and awakenings were recorded . RESULTS . Overall , in the prone position , infants slept longer , had greater sleep efficiency ( 89.5 % vs 72.5 % ) , and had more central apneas ( median : 5.6 vs 2.2 ) , but fewer obstructive apneas ( 0.5 vs 0.9 ) . The infants had more awakenings ( 9.7 vs 3.5 ) and arousals per hour ( 13.6 vs 9.0 ) when supine . There were similar findings in the bronchopulmonary dysplasia infants . CONCLUSIONS . Very prematurely born infants studied before neonatal unit discharge sleep more efficiently with fewer arousals and more central apneas in the prone position , emphasizing the importance of recommending supine sleeping after neonatal unit discharge for prematurely born infants", "To evaluate the influence of prematurity and postnatal age on the relationship between motor activity ( MA ) and sleep states , forty clinical ly and neurologically normal infants were recorded polygraphically and grouped according to their gestational ( GA , prematures : 39 - 41 weeks ) ages . Sleep states ( active : AS , and quiet : QS ) were defined by the concordance of EEG and rapid eye movement criteria . Movements of both upper ( UL ) and lower ( LL ) limbs were independently recorded . In all groups the amount of MA in both UL and LL clearly predominated in AS compared with QS ( p longest period without movement and the no-movement 20-sec epochs were significantly higher in QS than in AS ( p modifications and modulation of MA amount throughout the state were similar for PRT and FT groups : a ) in both groups a significant decrease of MA with advancing CA was observed ( p MA throughout the state was r and omly distributed regardless of CA . In QS , however , PRT were distinguishable from FT by the absence of : a ) a significant decrease of MA amount with advancing CA , together with a reduced increase of both the longest period without movements and the no-movement 20-sec epochs ; b ) prevalence of MA in LL compared with UL ; c ) modulation of the distribution of MA throughout the state", "This study investigated the prolonged effects on state behavior of theophylline administered to infants for apnea of prematurity . There were three groups : Four premature infants who had received theophylline in the preterm period , five premature infants who had not received theophylline , and twenty-eight normal fullterm infants . The Theophylline infants had been off the drug for at least one month prior to the beginning of the study . Sleep-wake states were observed in the home for seven-hour periods when all infants were the same corrected ages : two , three , four and five weeks post-term . Data from the portion of the day that the infants were alone were analysed for this study . The state organization of the Theophylline group differed significantly from those of the other groups . They exhibited more non-alert waking activity , more alert , more drowse or transition , and less active sleep than did the Non-Theophylline and Fullterm infants . The state distributions of the latter two groups did not differ . On the basis of similarities between the results of this study and of a previous animal study , it was concluded that theophylline altered the normal development of state organization in premature infants . These effects persisted long after the drug had cleared the body", "Purpose : Sleep and ongoing cycling of sleep states are required for neurosensory processing , learning , and brain plasticity . Many aspects of neonatal intensive care environments such as h and ling for routine and invasive procedures , bright lighting , and noise can create stress , disrupt behavior , and interfere with sleep in prematurely born infants . The study empirically investigated whether a 30-minute observation of infant sleep states and behavior could differentiate an intervention to promote sleep in premature infants with feeding difficulties relative to conventional care ( st and ard positioning , st and ard crib mattress [ SP ] ) . We included an intervention to determine the ability of the method to discriminate treatments and generate a benchmark for future improvements . The intervention , a conformational positioner ( CP ) , is contoured around the infant to provide customized containment and boundaries . To more fully verify the 30-minute observational sleep results , st and ard polysomnography was conducted simultaneously and sleep outcomes for the 2 modalities were compared . Subjects : In a r and omized crossover clinical trial , 25 infants , 31.5 ± 0.6 weeks ' gestational age and 38.4 ± 0.6 weeks at the study , with gastrointestinal conditions or general feeding difficulties used each intervention during an overnight neonatal intensive care unit sleep study . Methods : Infant sleep states and behaviors were observed during two 30-minute periods — that is , on the positioner and mattress — using the naturalistic observation of newborn behavior . Two certified developmental care nurses assessed sleep state , self-regulatory , and stress behaviors during 2-minute intervals and summed over 30 minutes . Sleep characteristics from st and ard polysomnography were measured at the time of behavior observations . Results : Infants on CP spent significantly less time in alert , active awake , or crying states by observation compared with SP . Surgical subjects spent more time awake , active awake , or crying and displayed a higher number of behavior state changes than the nonsurgical infants . The percentage of time in observed deep sleep and quiet sleep was correlated with both percentage sleep efficiency ( r = 0.78 ) and fewer state shifts per hour ( r = −0.65 ) from electroencephalogram ( EEG ) . Sleep efficiency by EEG was greater on CP versus SP . Conclusions : The CP enabled sleep compared with the st and ard mattress ( SP ) over 30-minute observation periods . Sleep status from behavioral observation was verified by st and ard EEG-based sleep techniques . Behavioral observation of sleep states may be a useful strategy for measuring the effectiveness of strategies to facilitate sleep in premature infants . Surgical subjects may benefit from additional interventions to promote sleep", "Aim : To study clinical ly relevant aspects of sleep behaviour in preterm children in comparison to term children . Methods : Longitudinal sleep behaviour data were collected prospect ively by structured interviews in 130 preterm and 75 control term children from birth to age 10 y. Results : No significant differences in sleep duration ( time in bed per 24 h ) , bedsharing , night wakings , bedtime resistance and sleep‐onset difficulties were found between preterm and term children", "Bathing is a routine care procedure that exposes preterm infants to prolonged h and ling , which could cause stress and potentially disrupt infants ' biobehavioral responses . The aim of this double-blind r and omized crossover trial was to compare the preterm infant 's body temperature , heart rate ( HR ) , peripheral capillary oxygen saturation ( SpO2 ) , salivary cortisol levels , and sleep-wake states during and after swaddled and conventional tub baths . Forty-three infants born at 32 to 36 weeks postmenstrual age , weighing 2225 g or less , were enrolled in the study . Infants were videotaped before and after each type of baths . The time interval between baths ranged from 24 to 72 hours to allow a washout period . Physiological , hormonal , and behavioral responses were collected at baseline and during recovery from baths . No significant differences in the mean body temperature , HR , SpO2 , salivary cortisol levels , and sleep-wake states between the bath types were observed in the baseline or recovery responses during the first 20 minutes after bath . Regardless of bath type , salivary cortisol levels showed a nonstatistical significant increase", "AIM To determine whether respiratory support via heated humidified high flow nasal cannulae ( HHHFNC ) results in infants spending a greater proportion of time in sleep compared to those receiving nasal continuous positive airway pressure ( NCPAP ) . METHODS A subgroup of infants enrolled in a r and omized controlled trial to compare HHHFNC or NCPAP post-extubation had sleep and wake activity measured by actigraphy for 72hours post-extubation . Activity diaries were completed contemporaneously to record episodes of infant h and ling . Actigraphy data were downloaded with known periods of h and ling excluded from the analysis . RESULTS 28 infants with mean gestation of 28.3weeks ( SD 2 ) and birth weight 1074 g ( SD 371 ) were studied . Infants receiving HHHFNC spent a lesser proportion of time in sleep 59.8 % ( SD 18.5 ) than those on NCPAP 82.2 % ( SD 23.8 ) p=0.004 . Infants receiving HHHFNC had a lower sleep efficiency and higher mean activity score than those on NCPAP ( p=0.003 , p=0.002 , respectively ) . CONCLUSION Infants receiving HHHFNC had a higher mean activity score and spent less time in sleep than those allocated NCPAP . Further study of sleep wake activity in preterm infants receiving respiratory support is required as this may impact on neurodevelopmental outcomes", "BACKGROUND The use of earmuffs can protect preterm infants against negative effects of high noise levels in the neonatal intensive care unit . This study was aim ed at assessing the effectiveness of the earmuffs on the physiologic and behavioral responses in preterm infants . METHODS A crossed over controlled trial was conducted at Aliasghar Hospital ( Tehran , Iran ) in 2014 . Thirty-six preterm infants cared in closed incubators , 18 cases wore a pair of silicon earmuffs in the first day and the others were worn it at the second day . During 2 consecutive days , all subjects were observed as their own controls ( without earmuffs ) . Physiologic ( body temperature , heart rate , respiratory rate , systolic , diastolic pressures , arterial Oxygen Saturation ) and behavioral responses ( according to the And erson behavioral state scoring system ) were assessed every 2 h for 8 h long during daytime for two consecutive days . RESULTS The application of earmuffs could decrease the rate of the heart and respiratory while could increase the amount of oxygen saturation ( p preterm infants with earmuffs had lower ABSS score and a better light sleep compared to those without earmuffs ( 2.38 ± 0.47 versus 4.8 ± 0.97 , p earmuffs reduces the level of noise in NICUs following by improving the preterm neonates ' physiological stability and behavioral states of ABSS ", "Objective There is a paucity of data relating to neurodevelopmental outcomes in infants born late and moderately preterm ( LMPT ; 32 + 0–36 + 6 weeks ) . This paper present the results of a prospect i ve , population -based study of 2-year outcomes following LMPT birth . Design 1130 LMPT and 1255 term-born children were recruited at birth . At 2 years corrected age , parents completed a question naire to assess neurosensory ( vision , hearing , motor ) impairments and the Parent Report of Children 's Abilities-Revised to identify cognitive impairment . Relative risks for adverse outcomes were adjusted for sex , socio-economic status and small for gestational age , and weighted to account for over-sampling of term-born multiples . Risk factors for cognitive impairment were explored using multivariable analyses . Results Parents of 638 ( 57 % ) LMPT infants and 765 ( 62 % ) controls completed question naires . Among LMPT infants , 1.6 % had neurosensory impairment compared with 0.3 % of controls ( RR 4.89 , 95 % CI 1.07 to 22.25 ) . Cognitive impairments were the most common adverse outcome : LMPT 6.3 % ; controls 2.4 % ( RR 2.09 , 95 % CI 1.19 to 3.64 ) . LMPT infants were at twice the risk for neurodevelopmental disability ( RR 2.19 , 95 % CI 1.27 to 3.75 ) . Independent risk factors for cognitive impairment in LMPT infants were male sex , socio-economic disadvantage , non-white ethnicity , preeclampsia and not receiving breast milk at discharge . Conclusions Compared with term-born peers , LMPT infants are at double the risk for neurodevelopmental disability at 2 years of age , with the majority of impairments observed in the cognitive domain . Male sex , socio-economic disadvantage and preeclampsia are independent predictors of low cognitive scores following LMPT birth", "Objective : Children with sleep disorders tend to experience attention problems , yet little is known about the relationship between sleep and attention in early development . This prospect i ve follow-up study investigated the longitudinal relationships between neonatal sleep , attention , and distraction in infants born preterm . Method : We used actigraphy and sleep-wake diaries in the neonatal intensive care unit ( NICU , N = 65 ) , attention orienting in a visual-recognition-memory task ( VRM ) at age 4 months , and structured observation of attention and distractibility at age 18 months . Results : Infants with poorer neonatal sleep ( n = 31 ) exhibited longer first gaze duration s in the VRM at 4 months and longer distraction episodes at 18 months relative to neonatal controls who slept well ( p neonatal sleep and gaze behavior at 4 months and distractibility at 18 months ; moreover , alterations in orienting attention at 4 months predicted the likelihood of being distracted during the second year of life . Conclusion : Findings underscore the importance of early sleep-wake and attention regulation in the development of distraction in infants born preterm", "Compared to r and omized controlled trials , non-r and omized studies of interventions might be biased in additional domains . As most previous tools for assessing risk of bias are not sufficient , a Cochrane working group has developed a new risk of bias tool called ROBINS-I ( Risk of bias in non-r and omized studies of interventions )" ]	41184776-06ff-11f0-808a-c43d1ab1c353
INTRODUCTION The optimization of enteral nutrition is a priority in preterm neonates worldwide . Probiotics are known to improve gut maturity and function in preterm neonates . To our knowledge , previous systematic review s have not adequately assessed the effects of probiotic supplementation on enteral nutrition in preterm neonates . OBJECTIVE We assessed the evidence on effects of probiotics on enteral nutrition in preterm neonates . DESIGN A systematic review of r and omized controlled trials ( RCTs ) of probiotic supplementation in preterm ( gestation was conducted . With the use of the Cochrane Neonatal Review Group strategy , we search ed the Cochrane Central Register of Controlled Trials , PubMed , EMBASE , and Cumulative Index of Nursing and Allied Health Literature data bases and proceedings of Pediatric Academic Society meetings in April 2014 . RESULTS A total of 25 RCTs ( n = 5895 ) were included in the review . A meta- analysis ( r and om-effects model ) of data from 19 of 25 trials ( n = 4527 ) estimated that the time to full enteral feeds was shorter in the probiotic group ( mean difference : -1.54 d ; 95 % CI : -2.75 , -0.32 d ; P fewer episodes of feed intolerance , better weight gain and growth velocity , decreased transition time from orogastric to breast feeds , and increased postpr and ial mesenteric flow . There were no adverse effects of probiotic supplementation . CONCLUSIONS Probiotics reduced the time to full enteral feeds in preterm neonates . Additional research is necessary to assess the optimal dose , duration , and probiotic strain or strains used specifically for facilitating enteral nutrition in this population	[ "Aim This study aims to compare the efficacy of orally administered Saccharomyces boulardii versus nystatin in prevention of fungal colonization and invasive fungal infections in very low birth weight infants . Method A prospect i ve , r and omized comparative study was conducted in preterm infants with a gestational age of ≤32 weeks and birth weight of ≤1,500 g. They were r and omized into two groups , to receive S. boulardii or nystatin . Skin and stool cultures were performed for colonization and blood cultures for invasive infections , weekly . Results A total of 181 infants were enrolled ( S. boulardii group , n = 91 ; nystatin group , n = 90 ) . Fungal colonization of the skin ( 15.4 vs 18.9 % , p = 0.532 ) and the stool ( 32.2 vs 27 % , p = 0.441 ) were not different between the probiotic and nystatin groups . Two patients had C and ida-positive blood culture in the nystatin group whereas none in the probiotic group . Feeding intolerance , clinical sepsis , and number of sepsis attacks were significantly lower in the probiotics group than in the nystatin group . Conclusion Prophylactic S. boulardii supplementation is as effective as nystatin in reducing fungal colonization and invasive fungal infection , more effective in reducing the incidence of clinical sepsis and number of sepsis attacks and has favorable effect on feeding intolerance", "Background : The increase in invasive fungal infections ( IFIs ) in neonatal intensive care unit ( NICU ) is jeopardizing the survival of preterm neonates . Probiotics modulating the intestinal microflora of preterm neonates may minimize enteral fungal colonization . Aims : This study was to examine whether probiotic supplementation in neonates reduced fungal septicemia . Material s and Methods : This prospect i ve , r and omized , double blind trial investigating the supplementation of preterm infants with a probiotic was done from May 2012 to April 2013 , with 112 subjects r and omized into two groups . Primary outcome : Decreased fungal colonization in gastrointestinal tract . Others : Incidence of late onset septicemia ; duration of the primary hospital admission ; number of days until full enteral feeds established . Results : Full feed establishment was earlier in probiotics group compared to placebo group ( P = 0.016 ) . The duration of hospitalization was less in the probiotic group ( P = 0.002 ) . Stool fungal colonization , an important outcome parameter was 3.03 ± 2.33 × 105 colony formation units ( CFU ) in the probiotics group compared to 3 ± 1.5 × 105 CFU in the placebo group ( P = 0.03 ) . Fungal infection is less in the study group ( P = 0.001 ) . Conclusion : The key features of our study were reduced enteral fungal colonization , reduce invasive fungal sepsis , earlier establishment of full enteral feeds , and reduced duration of hospital stay in the probiotics group", "BACKGROUND Probiotics are used for the prevention of necrotizing enterocolitis ( NEC ) because of their positive effects on intestinal motor function , modulation of inflammatory response , and mucosal barrier function . OBJECTIVE The objective was to assess whether the combined use of Lactobacillus casei and Bifidobacterium breve may prevent the occurrence of NEC stage ≥ 2 by the criteria of Bell in very-low-birth-weight preterm infants . DESIGN A double-blind , r and omized , controlled clinical trial was conducted in 231 preterm infants weighing from 750 to 1499 g at birth . The intervention group was composed of 119 infants who received human milk with probiotic supplementation ( B. breve and L. casei ) and a control group of 112 infants who received human milk containing no probiotics . The primary outcome was the occurrence of NEC stage ≥ 2 as defined by Bell 's modified criteria . RESULTS Four confirmed cases of NEC stage ≥ 2 by Bell 's criteria occurred only in the control group . CONCLUSIONS Oral supplementation of B. breve and L. casei reduced the occurrence of NEC ( Bell 's stage ≥ 2 ) . It was considered that an improvement in intestinal motility might have contributed to this result . This trial was registered at www.is rct in.org as number 67165178 ( International St and ard R and omized Controlled Trial )", "BACKGROUND Formula feeding or overweight in infancy may increase the later risk of obesity , but the mechanisms involved are uncertain . Because obesity is associated with high leptin concentrations relative to fat mass , programming of leptin concentrations may be one mechanism by which early nutrition influences later obesity . OBJECTIVE We tested the hypothesis that high nutrient intake or formula feeding in infancy programs greater leptin concentrations relative to fat mass in later life . DESIGN Serum leptin concentrations were measured by radioimmunoassay in 197 adolescents aged 13 - 16 y who were born preterm and r and omly assigned at birth to receive either a nutrient-enriched preterm formula or banked donated breast milk ( trial 1 ) or a preterm formula or a st and ard formula ( trial 2 ) . Fat mass was estimated with the use of bioelectrical impedance analysis . RESULTS After combining the results of trials 1 and 2 as planned , the ratio of leptin to fat mass was significantly greater in the children who received the preterm formula ( geometric : 0.84 microg x L(-1 ) x kg(-1 ) ) than in those who received st and ard formula or banked breast milk ( 0.62 microg x L(-1 ) x kg(-1 ) ; mean difference : 30.8 % ; 95 % CI for difference : 8.4 % , 53.2 % ; P = 0.007 ) . The difference between the diet groups remained significant after adjustment for age , sex , Tanner stage , social class , and fat mass . Human milk intake was significantly associated with lower leptin concentrations relative to fat mass in adolescence ( P = 0.023 ) , independent of potential confounding factors . CONCLUSION Programming of relative leptin concentrations by early diet may be one mechanism that links early nutrition with later obesity", "BACKGROUND Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly . Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer . AIM The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis ( NEC ) or sepsis in very low birth weight infants . STUDY DESIGN AND SUBJECTS A prospect i ve , double blind , placebo controlled trial was conducted in preterm infants ( ≤ 32 GWs , ≤ 1500 g birth weight ) . They were r and omized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo , starting with the first feed until discharged . OUTCOME MEASURES Necrotizing enterocolitis ( NEC ) or sepsis and NEC or death . RESULTS Birth weight and gestational age of the study ( n = 104 ) and the control ( n = 104 ) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks , respectively . Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group ( 9.6 % vs 7.7 % , p = 0.62 ; 28.8 % vs 23 % , p = 0.34 ) . Time to reach 100 mL/kg/day of enteral feeding ( 11.9 ± 7 vs 12.6 ± 7 days , p = 0.37 ) was not different between the groups . CONCLUSIONS Saccharomyces boulardii did not decrease the incidence of NEC or sepsis", "ABSTRACT The gastrointestinal microbiota of preterm infants in a neonatal intensive care unit differs from that of term infants . In particular , the colonization of preterm infants by bifidobacteria is delayed . A double-blind , placebo-controlled , r and omized clinical study was performed on 69 preterm infants to investigate the role of Bifidobacterium lactis Bb12 supplementation in modifying the gut microbiota . Both culture-dependent and culture-independent approaches were used to study the gut microbiota . Bifidobacterial numbers , determined by fluorescence in situ hybridization , were significantly higher in the probiotic than in the placebo group ( log10 values per g of fecal wet weight : probiotic , 8.18 + 0.54 [ st and ard error of the mean ] ; placebo , 4.82 + 0.51 ; P bifidobacterial numbers was also obtained with the culture-dependent method . The infants supplemented with Bb12 also had lower viable counts of Enterobacteriaceae ( log10 values of CFU per g of fecal wet weight : probiotic , 7.80 + 0.34 ; placebo , 9.03 + 0.35 ; P = 0.015 ) and Clostridium spp . ( probiotic , 4.89 + 0.30 ; placebo , 5.99 + 0.32 ; P = 0.014 ) than the infants in the placebo group . Supplementation of B. lactis Bb12 did not reduce the colonization by antibiotic-resistant organisms in the study population . However , the probiotic supplementation increased the cell counts of bifidobacteria and reduced the cell counts of enterobacteria and clostridia", "BACKGROUND It is known that the bifidobacteria flora play important roles in mucosal host defense and can prevent infectious diseases . Because bacterial population s develop during the first day of life , the authors examined whether the early administration of bifidobacteria has a positive effect on the health of low birth weight infants . METHODS The effects of oral administration of Bifidobacterium breve ( B. breve ) supplements were studied in a controlled trial with low birth weight infants ( average birth weight 1489 g ) . The infants were divided into three groups : Group A and B received a dose of 1.6 x 10(8 ) cells of B. breve supplement twice a day , commencing either from several hours after birth ( group A ) or 24 h after birth ( group B ) . Group C , the control group , received no supplement . RESULTS There were no significant differences in birth weight , treatment with antibiotics , and the starting time of breast-feeding among the three groups . A Bifidobacterium-predominant flora was formed at an average of 2 weeks after birth in group A and at an average of 4 weeks after birth in group B , while no Bifidobacterium was isolated in eight out of 10 infants in group C during the observation period of 7 weeks . In comparison between group A and B , Bifidobacterium was detected significantly earlier in group A , and the number of Enterobacteriaceae present in the infants at 2 weeks after birth was significantly lower in group A. CONCLUSION The results of the present study suggest that very early administration of B. breve to low birth weight infants is useful in promoting the colonization of the Bifidobacterium and the formation of a normal intestinal flora", "Objective : To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by C and ida species , of late-onset sepsis and neurological outcome in preterm newborns . Study Design : A prospect i ve study was conducted in 249 preterms who were subdivided into three groups : one group ( n=83 ) was supplemented with Lactobacillus ( L. ) reuteri , one group with L. rhamnosus ( n=83 ) and the other with no supplementation ( n=83 ) . The fungal colonization in the gastrointestinal tract , the late onset of sepsis and clinical parameters were recorded . A neurological structured assessment was further performed at 1 year of age . Result : C and ida stool colonization was significantly higher ( P L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups . Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group . Conclusion : The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by C and ida , in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms", "BACKGROUND AND OBJECTIVE : It has been suggested that probiotics may decrease infant mortality and nosocomial infections because of their ability to suppress colonization and translocation of bacterial pathogens in the gastrointestinal tract . We design ed a large double-blinded placebo-controlled trial using Lactobacillus reuteri to test this hypothesis in preterm infants . METHODS : Eligible infants were r and omly assigned during the first 48 hours of life to either daily probiotic administration or placebo . Infants in the intervention group were administered enterally 5 drops of a probiotic preparation containing 108 colony-forming units of L reuteri DSM 17938 until death or discharge from the NICU . RESULTS : A total of 750 infants ≤2000 g were enrolled . The frequency of the primary outcome , death , or nosocomial infection , was similar in the probiotic and placebo groups ( relative risk 0.87 ; 95 % confidence interval : 0.63–1.19 ; P = .376 ) . There was a trend toward a lower rate of nosocomial pneumonia in the probiotic group ( 2.4 % vs 5.0 % ; P = .06 ) and a nonsignificant 40 % decrease in necrotizing enterocolitis ( 2.4 % vs 4.0 % ; P = .23 ) . Episodes of feeding intolerance and duration of hospitalization were lower in infants ≤ 1500 g ( 9.6 % vs 16.8 % [ P = .04 ] ; 32.5 days vs 37 days [ P = .03 ] ) . CONCLUSIONS : Although L reuteri did not appear to decrease the rate of the composite outcome , the trends suggest a protective role consistent with what has been observed in the literature . Feeding intolerance and duration of hospitalization were decreased in premature infants ≤1500", "Background : Nosocomial infections endanger preterm infants . Objective : The aim of the present controlled r and omized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight ( VLBW ; Patients and Methods : In a r and omized controlled trial , 183 VLBW infants were stratified according to gestational age ( 23–26 and 27–29 weeks ) and early antibiotic therapy ( days 1–3 , yes or no ) and r and omly assigned to have their milk feedings supplemented with B. lactis ( 6 × 2.0 × 109 CFU/kg/day , 12 billion CFU/kg/day ) or placebo for the first 6 weeks of life . Primary outcome was the ‘ incidence density ’ of nosocomial infections defined as periods of elevated C-reactive protein ( > 10 mg/l ) from day 7 after initiation of milk feedings until the 42nd day of life ( number of nosocomial infections/total number of patient days ) . The main secondary outcome was necrotizing enterocolitis ( NEC ; ≧stage 2 ) . Results : There were 93 infants in the B. lactis group and 90 in the placebo group . There was no significant difference between the two groups with regard to the incidence density of nosocomial infections ( 0.021 vs. 0.016 ; p = 0.9 , χ2 test ) . There were 2 cases of NEC in the B. lactis group and 4 in the placebo group . None of the blood cultures grew B. lactis . Conclusion : In the present setting , B. lactis at a dosage of 6 × 2.0 × 109 CFU/kg/day ( 12 billion CFU/kg/day ) did not reduce the incidence density of nosocomial infections in VLBW infants . No adverse effect of B. lactis was observed", "BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe", "OBJECTIVE To determine whether routine probiotic administration to very preterm infants would reduce the incidence of necrotizing enterocolitis ( NEC ) without adverse consequences . STUDY DESIGN Since the end of July 2011 , we have administered a probiotic mixture to all admitted infants of We give 0.5 g of a mixture of 4 bifidobacteria ( Bifidobacterium breve , bifidum , infantis , and longum ) and Lactobacillus rhamnosus HA-111 [ corrected ] ( 2 × 10(9 ) colony-forming units ) per day , starting with the first feed , until the infant reaches 34 weeks . We compared complications among infants admitted during the first 17 months of routine use with those admitted during the previous 17 months . RESULTS Two hundred ninety-four infants received probiotics , and 317 infants formed the comparison group . Introduction of probiotics was associated with a reduction in NEC ( from 9.8 % to 5.4 % , P in death ( 9.8 % to 6.8 % ) , and a significant reduction in the combined outcome of death or NEC ( from 17 % to 10.5 % , P ( OR for NEC , 0.51 ; 95 % CI , 0.26 - 0.98 ; OR for death or NEC , 0.56 ; 95 % CI , 0.33 - 0.93 ) . There was no effect of probiotics on health care-associated infection . DISCUSSION A product that is readily available in North America , that has excellent quality control , and that contains strains similar to those that have been shown effective in r and omized controlled trials substantially reduced the frequency of NEC in our neonatal intensive care unit", "Background A r and omised , double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in the prevention of necrotising enterocolitis ( NEC ) in newborns weighing Methods We studied a group of 150 patients who were r and omised in two groups after parental consent was obtained , to receive either a daily feeding supplementation with a multispecies probiotic ( Lactobacillus acidophilus , Lactobacillus rhamnosus , Lactobacillus casei , Lactobacillus plantarum , Bifidobacteruim infantis , Streptococcus thermophillus ) 1 g per day plus their regular feedings or to receive their regular feedings with nothing added ( control group ) , over the period of January 2007 through June 2010 . Clinicians in care of the infants were blinded to the group assignment . Results The primary outcome was the development of NEC . Both groups were comparable , with no differences during hospitalisation , including the type of nutrition received . Blood cultures obtained from cases that developed sepsis did not reveal lactobacillus or Bifidobacteria growth . No differences were detected in terms of NEC risk reduction ( RR : 0.54 , 95 % CI 0.21 to 1.39 ) although we did observe a clear trend in the reduction of NEC frequency in the studied cases : 6 ( 8 % ) versus 12 ( 16 % ) in the control group . When the combined risk of NEC or death was calculated as a post hoc analysis , we found a significantly lower risk ( RR : 0.39 , 95 % CI 0.17 to 0.87 ) for the study group . Conclusions Probiotics may offer potential benefits for premature infants and are a promising strategy in the reduction of the risk of NEC in preterm newborns", "BACKGROUND Saccharomyces boulardii ( SB ) is a yeast that acts both as a probiotic and as a polyamine producer . Probiotics prevent the overgrowth of pathogens in the gut while polyamines enhance intestinal maturation . The aim of this r and omized study was to investigate the ability of SB to modify the gut microbial ecology and its function . METHODS A total of 87 healthy babies with gestational age 28 - 32 weeks were studied . They were r and omly assigned to receive a preterm formula to which SB or maltodextrins was added for 30 days . Evaluations were made on the following : SB tolerance and weight gain , faecal flora analysis , intestinal D-xylose absorption and faecal lipid excretion . RESULTS SB was well tolerated by the infants . There was no difference in weight gain between the two groups . Median log of colony forming units per gram of faeces for Escherichia coli and enterococci was significantly lower in the SB group [ E. coli : 2.67 ( 0.045 ) vs. 2.75 ( 0.058 ) , P number of bifidobacteria and staphylococci in the stools was significantly higher in the SB group [ bifidobacteria : 2.65 ( 0.083 ) vs. 2.27 ( 0.075 ) , P D-Xylose and lipid absorption was not improved by SB [ median blood D-xylose : 1.5 ( 0.4 ) mmol/l vs. 1.35 ( 0.3 ) mmol/l , P>0.1 ; median stool steatocrit : 64 % ( 3.05 % ) vs. 65 % ( 2.72 % ) P>0.5 ] . CONCLUSIONS An SB-supplemented formula is well tolerated by preterm infants , it has a beneficial effect on stool flora bringing it closer to that of breast fed babies but it does not improve D-xylose or lipid gut absorption", "Objective To evaluate the effect of oral Lactobacillus reuteri ( L reuteri ) first on the incidence and severity of Necrotising enterocolitis ( NEC ) and second on sepsis . Design Prospect i ve r and omised controlled study . Setting Tertiary neonatal intensive care unit . Patients and interventions Preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 g were included ( n=400 ) . Infants in the first group were given 100 million CFU/day ( 5 drops ) of lyophilised L reuteri ( DSM 17938 ) mixed in breast milk or formula , starting from first feeding until discharge . Participants in the control group were given a placebo . Main outcome measures To determine and compare the frequency of NEC and /or death after 7 days , frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Results There was no statistically significant difference between groups in terms of frequency of NEC stage ≥2 ( 4 % vs 5 % ; p=0.63 ) or overall NEC or mortality rates ( 10 % vs 13.5 % ; p=0.27 ) . Frequency of proven sepsis was significantly lower in the probiotic group compared to the control group ( 6.5 % vs 12.5 % ; p=0.041 ) . A significant difference was also observed with regard to rates of feeding intolerance ( 28 % vs 39.5 % ; p=0.015 ) and duration of hospital stay ( 38 ( 10–131 ) vs 46 ( 10–180 ) days ; p=0.022 ) . Conclusions Our results show that oral L reuteri does not seem to affect the overall rates of NEC and /or death in preterm infants followed up in the neonatal intensive care unit , and significant reductions were observed in the frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Trial registration number NCT01531179", "Background There are few carefully- design ed studies investigating the safety of individual probiotics approved under Investigational New Drug policies . Objectives The primary aim of this prospect i ve , double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 ( LR ) for 2 months is safe and well-tolerated . Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages , expression of toll-like receptors (TLR)-2 and −4 on circulating peripheral blood mononuclear cells ( PMBCs ) , cytokine expression by stimulated P BMC , and intestinal inflammation as measured by fecal calprotectin . Methods Forty healthy adults were r and omized to a daily dose of 5 × 108 CFUs of LR ( n = 30 ) or placebo ( n = 10 ) for 2 months . Participants completed a daily diary card and had 7 clinic visits during treatment and observation . Results There were no severe adverse events ( SAEs ) and no significant differences in adverse events ( AEs ) . There were no differences in P BMC subclasses , TLRs , or cytokine expression after treatment . The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment : 50 µg/g ( IQR 24–127 µg/g ) vs. 17 µg/g ( IQR 11–26 µg/g ) , p = 0.03 , although values remained in the normal clinical range ( 0–162.9 µg/g ) . LR vials retained > 108 CFUs viable organisms/ml . Conclusions LR is safe and well tolerated in adults , without significant changes in immunologic markers . There was a small but significant increase in fecal calprotectin , perhaps indicating some element of immune recognition at the intestinal level . Trial Registration Clinical Trials.gov", "Background Simple and safe strategies for the prevention of viral respiratory tract infections ( RTIs ) are needed . Objective We hypothesized that early prebiotic or probiotic supplementation would reduce the risk of virus-associated RTIs during the first year of life in a cohort of preterm infants . Methods In this r and omized , double-blind , placebo-controlled trial ( Clinical Trials.gov no. NCT00167700 ) , 94 preterm infants ( gestational age , ≥32 + 0 and ≤36 + 6 weeks ; birth weight , > 1500 g ) treated at Turku University Hospital , Turku , Finl and , were allocated to receive oral prebiotics ( galacto-oligosaccharide and polydextrose mixture , 1:1 ) , a probiotic ( Lactobacillus rhamnosus GG , ATCC 53103 ) , or placebo ( microcrystalline cellulose ) between days 3 and 60 of life . The primary outcome was the incidence of clinical ly defined virus-associated RTI episodes confirmed from nasal swabs by using nucleic acid testing . Secondary outcomes were the severity and duration of RTIs . Results A significantly lower incidence of RTIs was detected in infants receiving prebiotics ( rate ratio [ RR ] , 0.24 ; 95 % CI , 0.12 - 0.49 ; P probiotics ( RR , 0.50 ; 95 % CI , 0.28 - 0.90 ; P = .022 ) compared with those receiving placebo . Also , the incidence of rhinovirus-induced episodes , which comprised 80 % of all RTI episodes , was found to be significantly lower in the prebiotic ( RR , 0.31 ; 95 % CI , 0.14 - 0.66 ; P = .003 ) and probiotic ( RR , 0.49 ; 95 % CI , 0.24 - 1.00 ; P = .051 ) groups compared with the placebo group . No differences emerged among the study groups in rhinovirus RNA load during infections , duration of rhinovirus RNA shedding , duration or severity of rhinovirus infections , or occurrence of rhinovirus RNA in asymptomatic infants . Conclusions Gut microbiota modification with specific prebiotics and probiotics might offer a novel and cost-effective means to reduce the risk of rhinovirus infections ", "Background Probiotic supplementation significantly reduces the risk of necrotising enterocolitis ( NEC ) and all cause mortality in preterm neonates . Independent quality assessment is important before introducing routine probiotic supplementation in this cohort . Aim To assess product quality , and confirm that Bifidobacterium breve ( B. breve ) M-16V supplementation will increase fecal B. breve counts without adverse effects . Methods and Participants Strain identity ( 16S rRNA gene sequencing ) , viability over 2 year shelf-life were confirmed , and microbial contamination of the product was ruled out . In a controlled trial preterm neonates ( Gestation were r and omly allocated to either B. breve M-16V ( 3 × 109 cfu/day ) or placebo ( dextrin ) supplementation until the corrected age 37 weeks . Stool sample s were collected before ( S1 ) and after 3 weeks of supplementation ( S2 ) for study ing fecal B. breve levels using quantitative PCR ( Primary outcome ) . Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II . Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests , and McNemar and Wilcoxon signed-rank tests for paired comparisons . Results A total of 159 neonates ( Probiotic : 79 , Placebo : 80 ) were enrolled . Maternal and neonatal demographic characteristics were comparable between the groups . The proportion of neonates with detectable B. breve increased significantly post intervention : Placebo : [ S1:2/66 ( 3 % ) , S2 : 25/66 ( 38 % ) , p : [ S1 : 29/74 ( 40 % ) , S2 : 67/74 ( 91 % ) , p in both groups were below detection ( There were no adverse effects including probiotic sepsis and no deaths . NEC≥Stage II occurred in only 1 neonate ( placebo group ) . Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates . Trial Registration Australia New Zeal and Clinical Trial Registry ACTRN", "The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so , does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae , enterococci , yeasts or staphylococci , and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome . Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge . The infants were r and omised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks . The clinical features of the two groups of infants were similar . Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants . However , colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants", "BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation . Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth", "Studies were carried out on premature infants in the neonatal intensive care unit to determine the effect of feeding of lactobacilli on colonization of the gastrointestinal tract by antibiotic-resistant gram-negative enteric organisms . Thirty premature infants were matched by birth weight and gestational age , r and omized and fed double blind either lactobacilli-containing formula or non-lactobacilli-containing formula within 72 hours of delivery . The two study groups were screened weekly by culture for stool lactobacilli , for gram-negative bacteria and for antibiotic resistance of these bacteria . Lactobacilli were cultured from the stools of 13 of 15 patients receiving lactobacilli and from 3 of 15 patients not receiving lactobacilli ( P Gram-negative enteric organisms were isolated during 40 of the 86 weeks ( 47 % ) of hospitalization for patients receiving lactobacilli and during 28 of 57 weeks ( 49 % ) for patients not receiving lactobacilli . There was no significant difference between the study groups in the number of resistant organisms or in the proportion of resistant organisms per gram-negative enteric isolates ( 4 of 40 vs. 0 of 28 ) . These results suggest that facultative gram-negative enteric bacterial colonization , with either total or aminoglycoside-resistant strains , is not decreased by oral feedings of Lactobacillus acidophilus in premature infants", "Background : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population", "Objective : The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight ( ELBW ) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age ( PMA ) . Other important outcome measures , such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated . Study Design : We conducted a multicenter r and omized controlled double-blinded clinical study . The probiotics-supplementation ( PS ) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks ( PMA ) . The control ( C ) group received unsupplemented feedings . Infant weight and feeding volumes were recorded daily during the first 28 days of study period . Weights were also recorded at 34 weeks PMA . Result : A total of 101 infants were enrolled ( PS 50 versus C 51 ) . There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA ( PS group 58 % versus C group 60 % , ( P value 0.83 ) ) or in the average volume of feeding during 28 days after study entry ( PS group 59 ml kg−1 versus C group 71 ml kg−1 , ( P value 0.11 ) ) . Calculated growth velocity was higher in the PS group compared with the C group ( 14.9 versus 12.6 g per day , ( P value 0.05 ) ) . Incidences of necrotizing enterocolitis ( NEC ) , as well as mortality were similar between the two groups . Conclusion : Although probiotic-supplemented feedings improve growth velocity in ELBW infants , there was no improvement in the percentage of infants with growth delay at 34 weeks PMA . There were no probiotic-related adverse events reported", "Objective : To determine whether probiotics supplementation affects intestinal blood flow velocity in extremely low birth weight neonates . Study Design : In this r and omized , double-blind , placebo-controlled study , probiotics were added to the first enteral feeding and continued until discharge or 34 weeks postmenstrual age . Pulsed Doppler was used to measure prepr and ial and postpr and ial ( at 30 and 60 min ) time-averaged mean velocity ( TAMV ) , peak systolic velocity ( PSV ) and end diastolic velocity ( EDV ) during the second week of life after ⩾7 days of probiotics supplementation . Result : A total of 31 infants were studied , 15 were r and omized to the probiotic and 16 to the placebo groups . There was a significant postpr and ial increase in TAMV for the probiotic vs the placebo group ( P=0.035 ) , with PSV and EDV showing a trend . Demographic and clinical variables were similar between the groups . Conclusion : Probiotics administration significantly increases postpr and ial intestinal blood flow in extremely low birth weight preterm neonates when compared with the placebo group", "To fortify the biological role of milk formula has been suggested to use probiotics and prebiotics as functional components to mimic the effect of breast milk . The aim of this study was to evaluate the effects of prebiotic , probiotic added to a st and ard formula on gastrointestinal motility respect to placebo-formula . Cutaneous electrogastrography ( EGG ) and ultrasound gastric emptying ( GE ) were performed in 49 preterm newborns . 17 newborns were exclusively breast-fed ; 32 were r and omly assigned to receive prebiotic-added formula ( 0.8 g/dl of a mixture from scGOS and lcFOS , ratio 9:1 ) ( 10 ) , a probiotic-added formula ( L. reuteri at dose of 1x10(8 ) colony forming units ( CFU ) per day ) ( 10 ) , a formula with placebo ( 12 ) for 30 days . No difference was seen in the nutritional parameters and no adverse events were reported . After the intervention period , the prebiotic , probiotic , and breast milk groups showed a higher percentage of EGG slow wave propagation and faster gastric half emptying time respect to placebo group ( ANOVAon ranks p control : prebiotic , probiotic and breast-milk vs placebo formula p prebiotic , probiotic and breast-milk vs placebo formula p preterm infants with a formula supplemented with prebiotics or probiotics may stimulate gastric emptying and improve maturation of the EGG activity mimicking the effect of breast milk", "BACKGROUND In animals , acceleration of neonatal growth is thought to increase the later propensity to insulin resistance and non-insulin-dependent diabetes , whereas slow growth as a consequence of undernutrition is thought to have a beneficial effect . To test this hypothesis in people , we measured fasting concentrations of 32 - 33 split proinsulin , a marker of insulin resistance , in adolescents born preterm who had participated in r and omised intervention trials of neonatal nutrition , and in adolescents born at term . METHODS We determined fasting 32 - 33 split proinsulin concentration in participants aged 13 - 16 years born preterm and r and omised to receive a nutrient-enriched or lower-nutrient diet ( n=216 ) or in a reference group born at term ( n=61 ) . FINDINGS Fasting 32 - 33 split proinsulin concentration was greater in children given a nutrient-enriched diet ( geometric mean 7.2 pmol/L , 95 % CI 6.4 - 8.1 ) than in those given the lower-nutrient diet ( 5.9 pmol/L [ 5.2 - 6.4 ] ; mean difference 20.6 % [ 5.0 - 36.3 ] ; p=0.01 ) . Healthy babies born at term had similar fasting 32 - 33 split proinsulin concentrations ( 6.9 pmol/L ; 6.0 - 8.2 ) to the nutrient-enriched group . In non-r and omised analyses , fasting 32 - 33 split proinsulin concentration was associated with greater weight gain the first 2 weeks of life ( 13.2 % [ 5.4 - 20.9 ] change per 100 g weight increase ; p=0.001 ) independent of birthweight , gestation , neonatal morbidity , and demographic , anthropometric , and socioeconomic factors . INTERPRETATION Our results suggest that relative undernutrition early in life in children born preterm may have beneficial effects on insulin resistance", "BACKGROUND Colonization by C and ida species is the most important predictor of the development of invasive fungal disease in preterm neonates , and the enteric reservoir is a major site of colonization . We evaluated the effectiveness of an orally supplemented probiotic ( Lactobacillus casei subspecies rhamnosus ; Dicoflor [ Dicofarm spa ] ; 6 x 10(9 ) cfu/day ) in the prevention of gastrointestinal colonization by C and ida species in preterm , very low birth weight ( i.e. , METHODS Over a 12-month period , a prospect i ve , r and omized , blind , clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit . During the first 3 days of life , the neonates were r and omly assigned to receive either an oral probiotic added to human ( maternal or pooled donors ' ) milk ( group A ) or human milk alone ( group B ) for 6 weeks or until discharge from the NICU , if the neonate was discharged before 6 weeks . On a weekly basis , specimens obtained from various sites ( i.e. , oropharyngeal , stool , gastric aspirate , and rectal specimens ) were collected from all patients for surveillance culture , to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract . RESULTS The incidence of fungal enteric colonization ( with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site ) was significantly lower in group A than in group B ( 23.1 % vs. 48.8 % ; relative risk , 0.315 [ 95 % confidence interval , 0.120 - 0.826 ] ; P = .01 ) . The numbers of fungal isolates obtained from each neonate ( P = .005 ) and from each colonized patient ( P = .005 ) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001 - 1500 g. There were no changes in the relative proportions of the different C and ida strains . No adverse effects potentially associated with the probiotic were recorded . CONCLUSIONS Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by C and ida species among very low birth weight neonates", "Background / Objective : The identification of probiotic species involved in gut homeostasis and their potential therapeutic benefits have led to an interest in their use for preventing necrotizing enterocolitis ( NEC ) . Although bifidobacterium and lactobacilli sp. have been used to reduce the incidence of NEC in clinical trials . Lactobacillus sporogenes has not been used in the prevention of NEC in very low-birth weight infants yet . The objective of this study was to evaluate the efficacy of orally administered L sporogenes in reducing the incidence and severity of NEC in very low-birth weight ( VLBW ) infants . Subjects/ Methods : A prospect i ve , blinded , r and omized controlled trial was conducted in preterm infants with a gestational age of The infants in the study group were given L. sporogenes with a dose of 350 000 000 c.f.u . added to breast milk or formula , once a day , starting with the first feed until discharged . The infants in the control group were fed without L. sporogenes supplementation . The primary outcome measurement was death or NEC ( Bell 's stage ⩾2 ) . Results : A total of 221 infants were studied : 110 in the study group and 111 in the control group . There was no significant difference in the incidence of death or NEC between the groups . Feeding intolerance was significantly lower in the probiotics group than in the control group ( 44.5 % ( n : 49 ) vs 63.1 % ( n : 70 ) , respectively ; P=0.006 ) . Conclusions : L. sporogenes supplementation at the dose of 350 000 000 c.f.u/day is not effective in reducing the incidence of death or NEC in VLBW infants , however , it could improve the feeding tolerance ", "BACKGROUND Despite data relating body size in early life to later cardiovascular outcomes , the hypothesis that nutrition affects such outcomes has not been established . Breastfeeding has been associated with lower blood pressure in later life , but previous studies have not controlled for possible confounding factors by using a r and omised design with prospect i ve follow-up . We undertook such a study to test the hypothesis that early diet programmes blood pressure in later life in children r and omly assigned different diets at birth . METHODS Blood pressure was measured at age 13 - 16 years in 216 ( 23 % ) of a cohort of 926 children who were born prematurely and had participated at birth in two parallel r and omised trials in five neonatal units in the UK . Dietary interventions were : donated banked breastmilk versus preterm formula and st and ard term formula versus preterm formula . FINDINGS Children followed up at age 13 - 16 years were similar to those not followed up in terms of social class and anthropometry at birth . Mean arterial blood pressure at age 13 - 16 years was lower in the 66 children assigned banked breastmilk ( alone or in addition to mother 's milk ) than in the 64 assigned preterm formula ( mean 81.9 [ SD 7.8 ] vs 86.1 [ 6.5 ] mm Hg ; 95 % CI for difference -6.6 to -1.6 ; p=0.001 ) . In non-r and omised analyses , the proportion of enteral intake as human milk in the neonatal period was inversely related to later mean arterial pressure ( beta=-0.3 mm Hg per 10 % increase [ 95 % CI -0.5 to -0.1 ] ; p=0.006 ) . No differences were found in the term formula ( n=44 ) versus preterm formula ( n=42 ) comparison . INTERPRETATION Breastmilk consumption was associated with lower later blood pressure in children born prematurely . Our data provide experimental evidence of programming of a cardiovascular risk factor by early diet and further support the long-term beneficial effects of breastmilk", "BACKGROUND Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG ) and 49 received placebo . The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576", "AIM To investigate the colonisation withBifidobacterium breve of the bowels of very low birthweight ( VLBW ) infants . METHODS The adverse effects of B breve were examined in 66 VLBW infants ( preliminary study ) . A prospect i ve r and omised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years . Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants . The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody . RESULTS In the preliminary study there were no side effects attributable to the bacteria . Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73 % at 2 weeks of age , but only 12 % in the control group . Early administration of B brevesignificantly decreased aspirated air volume from the stomach and improved weight gain . CONCLUSIONS B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants , probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules", "BACKGROUND The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 ( B. bifidum ) on accelerating enteral feeding and bacterial colonization in very-low-birthweight ( VLBW ) infants . METHODS We conducted a single-center prospect i ve pilot study . Thirty-six VLBW infants were r and omly divided into two groups : group E , wherein B. bifidum was supplemented within 48 h of birth , and group L , wherein it was supplemented more than 48 h after birth . RESULTS Group E and group L reached a total feeding volume of 100 mL/(kg/day ) after 10 [ 7 - 13 ] days and 11 [ 10 - 15 ] days , respectively ( median [ quartile ] ) . The daily bodyweight gain in group E was significantly higher ( 21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day , P the fecal Bifidobacterium level between the groups quantitated with a real-time polymerase chain reaction assay at 1 and 4 weeks of age . However , the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth . The incidence of morbidities between the groups was similar . CONCLUSION The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity . Furthermore , the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth", "BACKGROUND Nutrient intakes meeting recommended dietary intakes ( RDIs ) take time to establish and once established are rarely maintained throughout hospital stay in preterm infants . A nutrient deficit , therefore , accrues . RDI are based on needs for maintenance and growth , with no provision to replace this deficit . We , therefore , hypothesized that postnatal malnutrition and growth retardation were inevitable in infants fed current RDI . METHODOLOGY Dietary intakes were prospect ively collected , by a single observer ( N.P. ) , on a daily basis in a group of preterm infants ( n = 105 ; birth weight Actual was subtracted from recommended energy ( 120 kcal/kg/day ) and protein ( 3 g/kg/day ) intakes and nutritional deficits calculated . Infants were weighed on admission and throughout hospital stay . The data were analyzed using a combination of repeated measures analysis of variance and stepwise regression analysis . RESULTS Nutrient intakes meeting current RDIs were rarely achieved during early life . By the end of the first week , cumulative energy and protein deficits were 406 + /- 92 and 335 + /- 86 kcal/kg and 14 + /- 3 and 12 + /- 4 g/kg in infants /=31 weeks . By the end of the fifth week , cumulative energy and protein deficits were 813 + /- 542 and 382 + /- 263 kcal/kg and 23 + /- 12 and 13 + /- 15 g/kg and the z scores were -1.14 + /-.6 and -.82 + /-.5 for infants at /=31 weeks . Stepwise regression analysis indicated that variation in dietary intake accounted for 45 % of the variation in changes in z score . CONCLUSIONS Preterm infants inevitably accumulate a significant nutrient deficit in the first few weeks of life that will not be replaced when current RDIs are fed . This deficit can be directly related to subsequent postnatal growth retardation.postnatal growth retardation , preterm infants", "BACKGROUND AND AIM Intestinal flora of preterms , dominantly presents with decreased amounts of physiological microbiota . This double blinded r and omized control trial compared the stool of bottle fed preterms , r and omized to receive lactobacillus rhamnosus GG ( LGG ) 6x109or placebo with formula feeding . STUDY DESIGN 46 enterally fed preterms were r and omized to receive probiotics or placebo within 0 - 3days after birth . All personnel were blinded to treatment assignment . Faecal sampling was preformed at day 7 , 21 , 42 . Presence of LGG colonization , somatic growth and length of hospital stay were recorded . RESULTS 60 patients were initially identified and enrolled but after exclusion criteria were applied , 21 babies were analyzed in the probiotic group and 26 in the placebo group . The number of lactobacillus were significantly higher ( p=0.014 ) on day 7 , and 21 ( p=0.024 ) in the study group , and so was the number of enterobacteriaceae on all study days ( p=0.004 , p=0.000 , p=0.000 ) , and Enterococcus sp on day 21 ( p=0.000 ) . The amount of sample s positive for staphylococci was significantly higher in the study group , on days 7 and 42 ( p=0.001 and 0.011 ) . We did not show a significant difference in weight gain upon discharge between the groups p=0.567 , 95 % CI ( -168 ; 305 ) or mean of hospital stay p=0.421 95 % CI ( -13.43;5.71 ) . CONCLUSIONS A preterm infant formula with an addition of probiotics leads to a rapid growth of LGG in the gut of bottle fed infants , but does not decrease the amount of pathogenic organisms , nor increase weight gain during enteral feeding , or decrease length of hospital stay", "OBJECTIVE To investigate the effect of dietary supplementation with a probiotic on feeding tolerance and gastrointestinal motility in healthy formula-fed preterm infants . STUDY DESIGN Thirty preterm newborns were enrolled ; 10 were exclusively breast-fed , and the remaining 20 were r and omly assigned in a double-blind manner to receive either Lactobacillus reuteri ATCC 55730 ( at dose of 1 x 10(8 ) colony forming units a day ) or placebo for 30 days . Clinical symptoms of gastrointestinal function ( regurgitation , vomiting , inconsolable crying , and evacuation ) and physiological variables ( gastric electrical activity and emptying ) were recorded before and after the dietary intervention . RESULTS Body weight gains per day were similar for the 3 groups , and no adverse events were recorded . Newborns receiving probiotics showed a significant decrease in regurgitation and mean daily crying time and a larger number of stools compared with those given placebo . Gastric emptying rate was significantly increased , and fasting antral area was significantly reduced in both the newborns receiving L. reuteri and breast-fed newborns compared with placebo . CONCLUSIONS Our results suggest a useful role for L. reuteri supplementation in improving feeding tolerance and gut function in formula-fed preterm newborns" ]	411847ee-06ff-11f0-808a-c43d1ab1c353
Background Total hip arthroplasty ( THA ) is increasingly performed in younger patients despite the lack of comprehensive assessment of long-term outcomes . We systematic ally review ed the contemporary literature to assess the 1 ) indications , 2 ) implant selection and long-term survivorship , 3 ) complication and reoperation rates and 4 ) radiographic and functional outcomes of primary THA in patients younger than 55 years . Methods We search ed the Embase and MEDLINE data bases for English- language articles published between 2000 and 2018 that reported outcomes of primary THA in patients younger than 55 years with a minimum follow-up duration of 10 years . Results Thirty-two studies reporting on 3219 THA procedures performed in 2434 patients met our inclusion criteria . The most common preoperative diagnoses were avascular necrosis ( 1044 [ 32.4 % ] ) , osteoarthritis ( 870 [ 27.0 % ] ) and developmental dysplasia of the hip ( 627 [ 19.5 % ] ) . Modular implants ( 3001 [ 93.2 % ] ) , cementless fixation ( 2214 [ 68.8 % ] ) and metal-on-polyethylene bearings ( 1792 [ 55.7 % ] ) were frequently used . The mean 5- and 10-year survival rates were 98.7 % and 94.6 % , respectively . Data on survival beyond 10 years were heterogeneous , with values of 27%–99.5 % at 10–14 years , 59%–84 % at 15–19 years , 70%–77 % at 20–24 years and 60 % at 25–30 years . Rates of dislocation , deep infection and reoperation for any reason were 2.4 % , 1.2 % and 16.3 % , respectively . The mean Harris Hip Score improved from 43.6/100 to 91.0/100 . Conclusion Total hip arthroplasty in patients younger than 55 years provides reliable outcomes at up to 10 years . Future studies should evaluate the outcomes of THA in this population at 15–20 years ’ follow-up	[ "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Background and purpose Femoral deformity associated with osteoarthritis is a challenge for both the surgeon and the implant . Many of the patients with these deformities are young . St and ard implants can be difficult to fit into these femurs . We prospect ively evaluated the outcome of custom uncemented femoral stems in young patients . Methods 61 consecutive patients ( 72 hips ) underwent surgery for osteoarthritis because of femoral deformity at a mean age of 35 ( 22–40 ) years . The patients received a CT3D-A custom-made femoral stem and an uncemented cup . The mean follow-up time was 14 ( 10–16 ) years . 2 patients died at 7 and 8 years after surgery , otherwise , none of the patients were lost to follow-up . Results At follow-up , the femoral prosthesis had not been revised in 59 patients ( 70 hips ) . 3 patients ( 3 hips ) had required revision surgery due to loosening of the acetabular component ; 2 hips were awaiting revision surgery for loosening of the acetabular cup . There were no cases of dislocation or infection . At review , all stems were considered stable according to the radiographic criteria . No migration or subsidence was observed on plain radiographs . Interpretation Our results are comparable to published results of custom stems regarding survival and outcome . Considering the young age and the deformities in this series of uncemented custom femoral stems , and the fact that there was follow-up of up to 16 years , the survival is remarkable . This technique appears to be a reasonable alternative in younger patients with femoral deformities", "Background The use of highly crosslinked polyethylene ( HXLPE ) is now commonplace for total hip arthroplasty . Hip simulator studies and short-term in vivo measurements suggest that the wear rate of some types of HXLPE is significantly less than conventional ultrahigh-molecular-weight polyethylene ( UHMWPE ) . However , there are few long-term data to support its use . Questions / purpose sThe aim of this study was to measure the long-term steady-state wear of HXLPE compared with UHMWPE liners in a prospect i ve , double-blind , r and omized controlled trial using radiostereometric analysis . Methods Fifty-four patients were r and omized to receive hip arthroplasties with either UHMWPE liners or HXLPE liners . Complete followup was available on 39 of these patients ( 72 % ) . All patients received the same cemented stem and an uncemented acetabular component . Three-dimensional penetration of the head into the socket was determined at 10 years using a radiostereometric analysis system , which has an in vivo accuracy of Oxford Hip Scores were compared between the groups . Results At 10 years there was significantly less wear of HXLPE ( 0.003 mm/year ; 95 % confidence interval [ CI ] , ± 0.010 ; SD 0.023 ; range , −0.057 to 0.074 ) compared with UHMWPE ( 0.030 mm/year ; 95 % CI , ± 0.012 ; p The volumetric penetration from 1 to 10 years for the UHMWPE group was 98 mm3 ( 95 % CI , ± 46 mm3 ; SD 102 mm3 ; range , −4 to 430 mm3 ) compared with 14 mm3 ( 95 % CI , ± 40 mm3 ; SD 91 mm3 ; range , −189 to 242 mm3 ) for the HXLPE group ( p = 0.01 ) . Conclusions This study demonstrates that HXLPE has little detectable steady-state in vivo wear . This may result in fewer reoperations from loosening ; however , careful clinical followup into the second decade still needs to be performed . Level of Evidence Level I , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence", "Background Anatomic short femoral prostheses with a prominent lateral flare have the potential to reduce stress-shielding in the femur through a more physiological stress distribution to the proximal femur . We present the design rationale of a new short uncemented , proximally fixed anatomic femoral implant and the study design of a prospect i ve multi-centre trial to collect long-term patient outcome and radiographic follow up data . Methods A prospect i ve surveillance study ( trial registry NCT00208555 ) in four European centres ( UK , Italy , Spain and Germany ) with a follow up period of 15 years will be executed . The recruitment target is 200 subjects , patients between the ages of 18 and 70 admitted for primary cementless unilateral THA will be included . The primary objective is to evaluate the five-year survivorship of the new cementless short stem . The secondary objectives of this investigation are to evaluate the long term survivorship and the clinical performance of the implant , the impact on the subjects health related Quality of Life and the affect of the prosthesis on bone mineral density . Peri- and postoperative complications will be registered . Clinical and radiographic evaluation of prosthesis positioning will be done post-operatively and at 3 , 6 , 12 , 24 , 60 , 120 and 180 months follow up . Discussion Shortening of the distal stem can maximise bone and soft tissue conservation . New stem types have been design ed to improve the limitations of traditional implants in primary THA . A new , uncemented femoral short stem is introduced in this paper . A long-term follow up study has been design ed to verify stable fixation and to research into the clinical outcome . The results of this trial will be presented as soon as they become available", "There have been comparatively few studies of the incidence of osteolysis and the survival of hybrid and cementless total hip replacements ( THRs ) in patients younger than 50 years of age . We prospect ively review ed 78 patients ( 109 hips ) with a hybrid THR having a mean age of 43.4 years ( 21 to 50 ) and 79 patients ( 110 hips ) with a cementless THR with a mean age of 46.8 years ( 21 to 49 ) . The patients were evaluated clinical ly using the Harris hip score , the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis score and the University of California , Los Angeles ( UCLA ) activity score . Radiographs and CT scans were assessed for loosening and osteolysis . The mean follow-up was for 18.4 years ( 16 to 19 ) in both groups . The mean post-operative Harris hip scores ( 91 points versus 90 points ) , the mean WOMAC scores ( 11 points versus 13 points ) and UCLA activity scores ( 6.9 points versus 7.1 points ) were similar in both groups . The revision rates of the acetabular component ( 13 % versus 16 % ) and the femoral component ( 3 % versus 4 % ) , and the survival of the acetabular component ( 87 % versus 84 % ) and the femoral component ( 97 % versus 96 % ) were similar in both groups . Although the long-term fixation of the acetabular metallic shell and the cemented and cementless femoral components was outst and ing , wear and peri-acetabular osteolysis constitute the major challenges of THR in young patients", "Background Because the clinical and radiographic performance of an ultrashort anatomic cementless stem has been investigated in only two r and omized controlled studies , well- design ed trials should aim for a thorough comparison of the outcomes of ultrashort anatomic cementless and conventional anatomic cementless stems . Questions / purpose sThe purpose s of this study were to compare ( 1 ) the clinical results , including Harris hip score , thigh pain , and WOMAC index score , ( 2 ) radiographic results , ( 3 ) bone mineral density ; and ( 4 ) proportions of patients undergoing revision of a THA using an ultrashort anatomic cementless stem versus a conventional anatomic cementless stem in the same patients who underwent bilateral sequential THAs under the same anesthetic . Methods Two hundred patients ( mean age , 53 years ; range , 26–54 years ) who underwent bilateral sequential THAs received an ultrashort anatomic cementless stem in one hip and a conventional anatomic cementless stem in the contralateral hip . From January 2004 to December 2005 , we performed 524 same-day bilateral short and conventional anatomic cementless THAs in 262 patients , of whom 212 ( 81 % ) participated in this study . Five patients were lost to followup before 2 years , five were lost between 2 to 10 years , and two were lost between 10 to 13 years , leaving 200 patients . Patients who had end-stage bilateral hip disease and were younger than 55 years were selected for inclusion . The predominant diagnoses were osteonecrosis ( 118 patients , 59 % ) and osteoarthritis ( 44 patients , 22 % ) . One hundred thirty-eight were men and 62 were women . At the time of each followup , the patients were assessed clinical ly and radiographically . In addition , each patient completed the WOMAC and the University of California Los Angeles ( UCLA ) activity scores . The minimum followup was 10 years ( mean , 11.8 years ; range , 10–13 years ) . Followups were done in person , with all images and followup clinic notes . Based on the power analysis , we estimated a sample size of 178 hips was needed in each group to detect a 3-point difference in the Harris hip score with 80 % power . Results At the latest followup , there were no differences between the two groups regarding the mean Harris hip scores ( 94 versus 94 points ; p = 0.189 ) , mean WOMAC scores ( 17 versus 16 points ; p = 0.191 ) , or mean UCLA activity scores ( 9 versus 9 points ; p = 0.381 ) . Two patients in the ultrashort stem group and one patient in the conventional stem group had severe ( 9 points ) thigh pain , and 30 patients ( 15 % ) in the conventional stem group had mild thigh pain ( 2 or 3 points ) after vigorous exercise . Bone mineral density in the ultrashort and conventional stem groups , respectively , was greater in the ultrashort stem group than in the conventional stem group . Bone mineral density in Zone 1 at 12 years was 3.29 versus 1.88 g/cm2 ( p = 0.021 ) , and 2.97 versus 0.91 g/m2 in Zone 7 ( p = 0.001 ) . With the numbers available , there were no differences between the stem design s in terms of the proportion undergoing revision ( one hip , 0.5 % , in the short-stem group versus one hip , 0.5 % , in the conventional group ; p = 1.881 ) . Conclusions At followup into the second decade , ultrashort stems showed no differences from conventional cementless stems in terms of vali date d outcomes scores or fixation , although less stress shielding was observed . Reduction of stress shielding may reduce the long-term risk of periprosthetic fracture , but this was not shown in our study .Level of Evidence Level I , therapeutic study", "We investigated the efficacy of combining highly cross-linked polyethylene with ceramic heads on further reduction in polyethylene wear compared with the combination with cobalt-chromium heads via PolyWare computer-assisted method . A prospect i ve cohort study was performed on 102 cementless total hip arthroplasties using Longevity ( Zimmer , Warsaw , Ind ) highly cross-linked polyethylene liners . Either 26-mm zirconia heads or 26-mm cobalt-chromium heads were r and omly used in 51 hips each . At a mean follow-up of 6.7 years , no significant differences were identified between the groups for total penetration rate and steady-state wear rate . Osteolysis was not observed in any hips in either group . In conclusion , no advantage was seen for the 26-mm zirconia head compared with the 26-mm cobalt-chromium head in this period", "Background The number of total hip arthroplasties in patients under 30 years is increasing over the years . Almost all of them will face at least one or more future revisions in their life . Therefore , the implant used should have a high survival rate , and needs to be easily revisable result ing in a low re-revision rate . Several studies have evaluated the outcome of total hip arthroplasties in patients under 30 years . However , only a few reported on the follow-up outcome of 10 years or more . In addition , none of these reports published data of the subsequent revisions of these implants within their original report . Methods We studied historically prospect i ve collected data of 48 consecutive patients ( 69 hips ) younger than 30 years , treated with a cemented primary total hip prosthesis between 1988 and 2004 . Since the last evaluation of this cohort , two patients were lost to follow-up . For all hip revisions in this cohort , again cemented implants were used , mostly in combination with bone impaction grafting . Kaplan-Meier survival curves at 10- and 15 years for the primary total hip arthroplasties and revisions were determined . Results The mean age at time of primary surgery was 25 years ( range , 16 to 29 years ) . Mean follow-up of the primary hips was 11.5 years ( range , 7 to 23 years ) . During follow-up 13 revisions were performed ; in 3 cases a two-stage total revision was performed for septic loosening and 9 cups were revised for aseptic loosening . There were no aseptic stem revisions . The 10 and 15-year survival rates with endpoint revision for aseptic loosening of the primary total hip were 90 % ( 95 % CI : 79 to 96 ) and 82 % ( 95 % CI : 65 to 92 ) respectively . None of our 13 subsequent revisions needed a re-revision within 10 years after re-implantation . Conclusions Cemented total hip implants in patients under 30 years have an encouraging outcome at 10 and 15 years after surgery in these young patients . The 13 revised hips , treated with bone grafting and the third generation cement technique , were performing well with no re-revisions within ten years after surgery" ]	41184866-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Menopause is a critical phenomenon in women 's life . After cardiac diseases , menopause is the second major cause of living with a disability in 45 - 60 year old women . The majority of women will experience bothersome vasomotor symptoms ( VMS ) . Menopausal hormone therapy ( MHT ) is the most effective treatment for these symptoms . The objective of this review is to focus on hormone therapy for relieving postmenopausal vasomotor symptoms . METHODS For this systematic review , we primarily explored 125 papers published about hormone therapy for VMS from 2001 to 2015 by search ing with combinations of the keywords in various data bases . Among those , 59 papers met the initial search criteria and among them , 9 papers were potentially retrievable and review ed . All included studies used estrogen formulations in the management of VMS . RESULTS Nine studies met all inclusion criteria . All studies assessed the effects of hormone replacement therapy on VSM . The results showed that low-dose oral and transdermal estrogen in all dose ranges were more likely than placebo to decrease the frequency of VMS . Indeed , the nanostructured formulation was safe and effective in relieving the symptoms of menopause . The mean daily decrease in the number of hot flashes from baseline was found in the studies . CONCLUSION MHT has a complex pattern . Underst and ing the natural history of VMS , and the risks and benefits of both hormonal therapies , helps to individualize management plans . Low-dose estrogen-based therapies can be the most effective regimens to relieve VMS . These medications can be used by different administration routes and formulations	[ "OBJECTIVE : To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone ( 10 % ) combined with estriol ( 0.1 % ) + estradiol ( 0.25 % ) for relieving postmenopausal symptoms . METHODS : A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern . Confocal Raman spectroscopy of hormones in skin layers was performed . Clinical parameters , serum concentrations of estradiol and follicle-stimulating hormone , blood pressure , BI-RADS classification from bilateral mammography , and symptomatic relief were compared between baseline and 60 months post-treatment . Clinical trials.gov : NCT02033512 . RESULTS : An improvement in climacteric symptoms was reported in 92.5 % of women evaluated before and after 60 months of treatment . The serum concentrations of estradiol and follicle-stimulating hormone changed significantly ( p values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women . No adverse health-related events were attributed to this hormone replacement therapy protocol . CONCLUSION : The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause . This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women", "Objective : This study examined whether use of complementary and alternative ( CAM ) therapies during the menopause transition varied by ethnicity . Design : The Study of Women 's Health Across the Nation is a prospect i ve cohort study following a group of 3,302 women from five racial/ethnic groups at seven clinical sites nationwide . Using longitudinal data encompassing 6 years of follow-up , we examined trends in use of five categories of CAM ( nutritional , physical , psychological , herbal , and folk ) by menopause status and ethnicity . To account for potential secular trends in CAM use or availability , we also evaluated the trends in CAM use over calendar time . Results : Approximately 80 % of all participants had used some form of CAM at some time during the 6-year study period . White and Japanese women had the highest rates of use ( 60 % ) , followed by Chinese ( 46 % ) , African American ( 40 % ) , and Hispanic ( 20 % ) women . Overall use of CAM therapy remained relatively stable over the study period . In general , CAM use did not seem to be strongly associated with change in menopause transition status . Use of CAM among white women did not change with transition status . Among Chinese and African American participants , we observed an increase in CAM use as women transitioned to perimenopause and a decrease in use of CAM with transition to postmenopause . Among Hispanic and Japanese women , we observed a decrease in use of CAM in early perimenopause , followed by an increase as women entered late perimenopause and a decrease as they progressed to postmenopause . Patterns of use for the five individual types of CAM varied . White women had relatively stable use of all CAM therapies through the transition . Japanese women decreased use of nutritional and psychological remedies and increased use of physical remedies as they transitioned into late perimenopause . Among African American women , use of psychological remedies increased as they progressed through menopause . Conclusions : Although CAM use did vary in some ethnic groups in relation to advancing menopause status , there was no evidence of influence of calendar time on CAM use . Patterns of CAM use during menopause are likely to be driven by personal experience , menopausal health , and access to therapies . Women 's personal preferences should be taken into consideration by healthcare providers for medical decision making during menopause and throughout the aging process", "OBJECTIVE To examine the impact of participation in a psycho-educational program on women 's attitudes toward menopause , the perceived severity of their symptoms , and the association between the two . DESIGN Quasi-experimental . Data were gathered at baseline and 3 months after termination of the program . SETTING Two health maintenance organization clinics . PARTICIPANTS Eighty-two healthy 40- to 60-year-old women who chose to participate in the study . Thirty-six women participated in the program , and 46 women comprised the control group . INTERVENTION Program participants met for 10 weekly sessions to receive information from a professional team on subjects related to menopause and to share and discuss their experiences . MAIN OUTCOME MEASURES Attitudes toward menopause and severity of menopause symptoms . RESULTS The more negative the attitudes , the higher was the severity of symptoms . Participants reported significant improvements in attitudes and reductions in symptom severity compared to their own baseline scores and compared with the control group . CONCLUSIONS Participation in a program that combines delivery of information and processing of experiences on the cognitive , emotional , and social levels may improve women 's attitudes toward menopause and ease the perceived severity of their symptoms , thereby increasing quality of life", "Menopause impacts 25 million women world wide each year , and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030 . Menopause has been associated with symptoms of hot flashes , night sweats , dysphoric mood , sleep disturbance , and conditions of cardiovascular disease , depression , osteoporosis , osteoarthritis , depression , dementia , and frailty . Conventional hormone replacement therapy results in increased thrombotic events , and an increased risk of breast cancer and dementia as evidence d in large prospect i ve clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women 's Health Initiative . A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors . Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile , yet long-term studies of this treatment model are lacking . The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol , estradiol , progesterone , DHEA , and testosterone on cardiovascular biomarkers , hemostatic , inflammatory , immune signaling factors ; quality -of-life measures ; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care . A prospect i ve , cohort , closed-label study received approval from the Human Subjects Committee . Recruitment from outpatient clinics at an academic medical center and the community at large result ed in three hundred women giving signed consent . Seventy-five women who met strict inclusion /exclusion criteria were enrolled . Baseline hormone evaluation was performed along with baseline experimental measures . Following this , women received compounded transdermal bioidentical hormone therapy of BiEst ( 80%Estriol/20%Estradiol ) , and /or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women . The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic , ischemic , or neuronal injury . Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of and rogens of DHEA and Testosterone if indicated . Experimental subjects were monitored for 36 months . Baseline , 2-month , and annual values were obtained for : blood pressure , body mass index , fasting glucose , Homeostasis Metabolic Assessment of Insulin Resistance ( HOMA-IR ) , fasting triglycerides , total Factor VII , Factor VIII , fibrinogen , Antithrombin III , Plasminogen Activator Inhibitor1(PAL-1 ) , C-reactive protein ( CRP ) , Interleukin-6 ( IL-6 ) , Matrix Metalloproteinase-9 ( MMP-9 ) , Tumor Necrosis Factor-alpha ( TNF ) , Insulin-like Growth Factor ( IGF-1 ) , and sex steroid levels . Psychosocial measures included : Greene Climacteric Scale , Visual Analog Pain Scale , Hamilton Anxiety Scale , Hamilton Depression Scale , Holmes Rahe Stress Scale , Job Strain , and Home Strain . Health outcome measures included the number of prescribed medications used , number of co-morbidities , and endometrial thickness in postmenopausal women with intact uteri . Subjects receiving compounded transdermal bioidentical hormone therapy showed significant favorable changes in : Greene Climacteric Scale scores , Hamilton Anxiety Scale , Hamilton Depression Scale , Visual Analog Pain Scale , fasting glucose , fasting triglycerides , MMP-9 , C-reactive Protein , fibrinogen , Factor VII , Factor VIII , Insulin-Like Growth Factor 1 , and health outcomes of co-morbidities and a number of prescribed medications . Antithrombin III levels were significantly decreased at 36 months . All other measures did not exhibit significant effects . Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women . Cardiovascular biomarkers , inflammatory factors , immune signaling factors , and health outcomes were favorably impacted , despite very high life stress , and home and work strain in study subjects . The therapy did not adversely alter the net prothrombotic potential , and there were no associated adverse events . This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in population s with high perceived stress and a history of stressful life events prior to , or during the menopausal transition", "Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy ; however , clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking . The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor , mood , and other quality -of-life symptoms in post-menopausal women . This was a prospect i ve , observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1 , 2003 and October 1 , 2010 in a community pharmacy . Data collection included patient demographics , comorbidities , hormone regimens , and therapeutic outcomes . Patients rated their vasomotor , mood , and quality -of-life symptoms as absent , mild , moderate , or severe at baseline , at one to three months follow-up , and three to six months follow-up . Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables . Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test . A total of 200 patients met study criteria ; 160 received topical bioidentical hormone replacement therapy , and 40 received sublingual bioidentical hormone replacement therapy . Most sublingually-treated patients ( 70 % ) received an estrogen combination and 100 % received progesterone . Nearly half ( 43 % ) of the topically treated patients received an estrogen combination ( 43 % ) and 99 % received progesterone . The percentage of sublingually treated patients reporting \" moderate \" or \" severe \" symptoms was significantly reduced at one to three months follow-up for the following target symptoms : hot flashes ( 31 % , P = 0.04 ) , night sweats ( 38 % , P irritability ( 36 % , P = 0.01 ) , anxiety ( 42 % , P emotional lability ( 38 % , P sleep disturbances ( 35 % , P memory loss ( 35 % , P = 0.04 ) , fatigue ( 33 % , P = 0.04 ) , and libido ( 26 % , P = 0.03 ) . Similar reductions were seen at three to six months follow-up compared to baseline . Patients who received topical therapy did not experience significant symptom reductions at one to three months follow-up ; however , significant symptom reduction was seen at three to six months for the following : emotional lability ( 31 % , P irritability ( 29 % , P = 0.02 ) , and night sweats ( 20 % , P = 0.04 ) . Compounded sublingual bioidentical hormone replacement therapy is effective in reducing vasomotor , mood , and quality -of-life symptoms experienced in post-menopausal women . Topical therapy does not appear to improve symptoms as extensively or rapidly as sublingual therapy", "BACKGROUND Hot flashes are frequent in postmenopausal breast cancer patients , especially when treated with tamoxifen . Estrogen replacement therapy is the most effective treatment for hot flashes , but its use is controversial in breast cancer survivors . Progestins may offer a good alternative for the control of hot flashes in this setting ; in particular , oral megestrol acetate has been proven effective in a r and omized , placebo-controlled clinical trial . With the aim of further improving these results , we have design ed a r and omized study comparing oral megestrol acetate with depot intramuscular ( i.m . ) medroxyprogesterone acetate ( MPA ) for the control of hot flashes in postmenopausal patients with a history of breast cancer . PATIENTS AND METHODS Seventy-one postmenopausal patients were r and omized to receive an i.m . injection of depot MPA 500 mg on days 1 , 14 and 28 , or oral megestrol acetate 40 mg daily for 6 weeks . Patients recorded daily the number and severity of their hot flashes ; response was defined as a > or = 50 % decrease in the number and severity of hot flashes . RESULTS At week 6 , hot flashes were reduced by 86 % on average in the whole group of patients , without significant differences between the two progestins . Response was obtained by 75 and 67 % of patients receiving MPA or megestrol , respectively ( P = 0.5 ) . Responders were followed to assess maintenance of response ( without further treatment ) , which was significantly better with i.m . MPA : in this group , 89 % of responders still showed a benefit at week 24 , compared with 45 % in the megestrol group ( P = 0.03 ) . CONCLUSIONS Our study shows that a short cycle of i.m . depot MPA injections provides significant and long-lasting relief from postmenopausal hot flashes in patients with a history of breast cancer , offering an alternative to estrogen replacement therapy or prolonged administration of oral megestrol", "Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause" ]	411848de-06ff-11f0-808a-c43d1ab1c353
Some believe that certain patients with intermittent claudication may be unsuitable for supervised exercise therapy ( SET ) , based on the presence of comorbidities and the possibly increased risks . We conducted a systematic review ( MEDLINE , EMBASE and CENTRAL ) to summarize evidence on the potential influence of diabetes mellitus ( DM ) on the response to SET . R and omized and nonr and omized studies that investigated the effect of DM on walking distance after SET in patients with IC were included . Considered outcome measures were maximal , pain-free and functional walking distance ( MWD , PFWD and FWD ) . Three articles met the inclusion criteria ( n = 845 ) . In one study , MWD was 111 meters ( 128 % ) longer in the non-DM group compared to the DM group after 3 months of follow-up ( p = 0.056 ) . In a second study , the non-DM group demonstrated a significant increase in PFWD ( 114 meters , p ⩽ 0.05 ) after 3 months of follow-up , whereas there was no statistically significant increase for the DM group ( 54 meters ) . On the contrary , the largest study of this review did not demonstrate any adverse effect of DM on MWD and FWD after SET . In conclusion , the data evaluating the effects of DM on SET were inadequate to determine if DM impairs the exercise response . While trends in the data do not suggest an impairment , they are not conclusive . Practitioners should consider this limitation when making clinical decisions	[ "OBJECTIVE Determine the efficacy of a home-based walking intervention to improve walking ability and quality of life in people with diabetes and peripheral arterial disease ( PAD ) . RESEARCH DESIGN AND METHODS We conducted a r and omized , controlled , single-blind trial within university-affiliated clinics in our local community . We r and omized 145 participants ( 45 women ) with diabetes and PAD to our intervention — a 6-month behavioral intervention targeting levels of readiness to engage in routine walking for exercise — versus attention control . Our primary outcome was 6-month change in maximal treadmill walking distance . Secondary outcomes included 3-month change in maximal walking distance , lower limb function ( i.e. , walking impairment scores ) , quality of life ( Medical Outcomes Short Form Survey ) , exercise behaviors , depressive symptoms , and self-efficacy at 3 and 6 months . RESULTS The mean age of participants was 66.5 ( SD 10.1 ) years . Intervention and control groups did not differ significantly in 6-month change in maximal treadmill walking distance ( average [ SE ] 24.5 [ 19.6 ] meters vs. 39.2 [ 19.6 ] meters ; P = 0.60 ) . Among secondary outcomes , for the intervention and control groups , respectively , average walking speed scores increased by 5.7 [ 2.2 ] units and decreased by 1.9 [ 2.8 ] units ( P = 0.03 ) ; the mental health quality of life subscale score increased by 3.2 [ 1.5 ] and decreased by 2.4 [ 1.5 ] units ( P = 0.01 ) . CONCLUSIONS A home-based walking intervention did not improve walking distance but did improve walking speed and quality of life in people with diabetes and PAD . Clinicians should consider recommending home-based walking therapy for such patients", "AIMS To determine if type 2 diabetes mellitus ( T2D ) differentiates endothelial function and plasma nitrite response ( a marker of nitric oxide bioavailability ) during exercise in peripheral arterial disease ( PAD ) subjects prior to and following 3 months supervised exercise training ( SET ) . METHODS In subjects with T2D+PAD ( n = 13 ) and PAD-only ( n = 14 ) , endothelial function was measured using brachial artery flow-mediated dilation . On a separate day , venous blood draws were performed at rest and 10 min following a symptom-limited grade d treadmill test ( SL-GXT ) . Plasma sample s were snap-frozen for analysis of nitrite by reductive chemiluminescence . All testing was repeated following 3 months of SET . RESULTS Prior to training both groups demonstrated endothelial dysfunction , which was correlated with a net decrease in plasma nitrite following a SL-GXT ( p ≤ 0.05 ) . Following SET , the PAD-only group demonstrated an improvement in endothelial function ( p ≤ 0.05 ) and COT ( p ≤ 0.05 ) , which was related to a net increase in plasma nitrite following the SL-GXT ( both p ≤ 0.05 ) . The T2D+PAD group had none of these increases . CONCLUSIONS T2D in the presence of PAD attenuated improvements in endothelial function , net plasma nitrite , and COT following SET . This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET", "OBJECTIVE The purpose of this study was to determine longitudinal predictors of impaired mobility and physical disability in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS We studied patients with type 2 diabetes who participated in a prospect i ve , community-based study . A wide range of baseline variables were examined to determine whether they predicted future difficulties with 1 ) mobility and 2 ) basic activities of daily living ( ADLs ) in patients free of ADLs difficulty at baseline . To study mobility impairment , subjects with baseline mobility problems were also excluded . RESULTS After an average 4.6 + /- 2.3 and 4.8 + /- 2.3 years of follow-up in 818 and 934 patients , respectively , 28.5 % of subjects had developed new mobility impairment and 18.1 % had developed new ADL disability . In Cox proportional hazards models , the risk of mobility impairment was significantly increased by older age ( 6%/year ) , peripheral neuropathy ( 40 % increase ) , stroke history ( 123 % ) , insulin treatment ( 117 % ) , albuminuria , and arthritis ( 82 % ) ; taking exercise and being married lowered the risk ( by 39 and 32 % , respectively ) . The risk of new ADL disability was increased by baseline mobility problems ( 222 % increase ) , stroke ( 92 % ) , claudication ( 67 % ) , and depression ( 41 % ) and was also influenced by age , smoking , lack of exercise , non-fluency in English , and indigenous Australian ethnicity . CONCLUSIONS Both mobility impairment and ADL disability in type 2 diabetes have multiple causes that are due to diabetes complications and common comorbidities . The specific causes of each functional problem are largely distinct , and different approaches may be required to prevent their onset or progression", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "PURPOSE This study was performed to test the efficacy of a supervised , hospital-based exercise program compared with a home-based exercise program involving minimal supervision , for both walking ability and quality of life measures in patients with exercise-limiting intermittent leg claudication . METHODS Twenty-one patients were assigned r and omly to 12 weeks of supervised exercise or to a home-based exercise group . After 12 weeks the participants in the supervised group transitioned to a home-based program . Both groups were then reevaluated at the end of 24 weeks . The initial claudication distance ( ICD ) and absolute claudication distance ( ACD ) on progressive treadmill exercise was measured at baseline , 12 weeks , and 24 weeks . Additionally , self-reported quality of life status was evaluated using the MOS SF-36 question naire . RESULTS Each group improved ( P ACD from baseline to 12 weeks , which was sustained at the 24-week follow-up . Both groups experienced similar long-term improvements ( P ACD ( 521.5 + /- 253.4 meters to 741.9 + /- 365.6 meters for the supervised group , 532.2 + /- 263.5 meters to 715.0 + /- 394.4 meters in the home group , P not significant , between groups ) . The supervised group experienced a greater improvement ( P ICD after 12 weeks than the home group but not at 24 weeks . The on-site group also experienced significant improvements in ICD after 24 weeks ( P self-reported physical function or mental health as assessed by the MOS SF-36 . CONCLUSION A structured exercise program was more effective in improving the ICD over a 24-week period than a less formal , home-based program . However , if patients are screened properly and receive adequate instruction , a home-based program can be a safe , low-cost alternative providing similar long-term ( 24 weeks ) exercise benefits in ACD", "OBJECTIVE Walking training ( WT ) is an established treatment for patients with intermittent claudication ( IC ) . Abnormalities specific to diabetes , such as a relative preponderance of distal lesions and the contribution of microcirculatory disease , might well influence the results of WT . We compared changes in walking distance during WT in diabetic patients with those in nondiabetic control subjects . RESEARCH DESIGN AND METHODS In consecutive patients with limiting IC and proven peripheral vascular disease , 33 patients with diabetes were compared with 136 control subjects during a half-year supervised WT program . Walking parameters were determined every 2 months , while vascular parameters were obtained at the start and end of the program . RESULTS Of the 33 diabetic patients , 25 ( 76 % ) completed the program , as did 87 of the 136 ( 64 % ) control subjects . Thereafter , the symptom-free walking distance and the maximum walking distance ( MWD ) were significantly increased in diabetic patients from 142 + /- 30 to 339 + /- 57 m and from 266 + /- 39 to 603 + /- 52 m , respectively , and in control subjects from 126 + /- 8 to 400 + /- 39 m and from 292 + /- 18 to 628 + /- 36 m , respectively . The relative gain in MWD was 88 % greater in those with diabetes . The vascular parameters were comparable for both groups before and after WT . CONCLUSIONS WT is an effective treatment for IC , with a greater relative gain in diabetic patients ", "OBJECTIVES This study was conducted to determine the role of insulin-dependent and noninsulin-dependent diabetes in the prognosis of patients after myocardial infa rct ion and treatment with fibrinolytic agents . BACKGROUND Several studies have shown that diabetic patients have a high mortality rate after acute myocardial infa rct ion . However , the impact of diabetes on survival in patients treated with fibrinolytic agents is still undefined . It is also not known whether the type of diabetes or gender affects prognosis . METHODS We analyzed prevalence and prognostic significance of a history of diabetes in patients enrolled in the GISSI-2 study , all of whom received fibrinolytic agents . The incidence of deaths in the hospital and at 6 months after study entry was computed for patients without diabetes and for insulin-dependent and noninsulin-dependent diabetic patients ; relative risks were evaluated by univariate and multivariate analysis . RESULTS Information on diabetic status was available for 11,667 patients , 94.2 % of those r and omized in the GISSI-2 study . The prevalence of diabetes was higher in women than in men ( 8.75 % vs. 1.85 % , p fibrinolytic agent did not affect mortality rates ; the increase in in-hospital mortality of diabetic patients was moderate and similar for men with insulin- and noninsulin-dependent diabetes ( 8.7 % and 10.1 % , respectively , vs. 5.8 % in nondiabetic patients ) ; in women , mortality was markedly higher for insulin-dependent and only slightly higher for noninsulin-dependent diabetic patients ( 24.0 % and 15.8 % , respectively , vs. 13.9 % for nondiabetic patients ) . The adjusted relative risks were 1.9 ( 95 % confidence interval 1.2 to 2.9 ) for insulin-dependent diabetic women and 1.4 ( 95 % confidence interval 1.1 to 1.8 ) for noninsulin-dependent diabetic men . The mortality rate after discharge showed a similar gender difference , and in insulin-dependent diabetic women , prognosis was ominous even in the absence of left ventricular damage before discharge . CONCLUSIONS A history of diabetes is associated with a worse prognosis after myocardial infa rct ion , even in patients treated with fibrinolytic agents . Gender and type of diabetes appear to be critical in affecting survival . In men , both insulin-dependent and noninsulin-dependent diabetes are associated with a moderately higher mortality rate ; in women , insulin-dependent diabetes is , in itself , a strong risk factor for death after myocardial infa rct ion", "OBJECTIVE The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients . RESEARCH DESIGN AND METHODS R and omly selected lower-extremity angiograms were examined according to the Bollinger system . Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died . RESULTS A total of 136 arteriograms obtained between 1992 and 1996 were analyzed . The age ( mean + /- SD ) of the patients was 64.7 + /- 10.8 years . Diabetic patients ( 43 % ) and nondiabetic patients were of similar age ( 63.9 + /- 10.4 vs. 65.3 + /- 11.1 years , P = 0.43 ) , with a similar history of smoking ( 81.0 vs. 76.9 % , P = 0.26 ) , ischemic heart disease ( 41.4 vs. 37.2 % , P = 0.54 ) , and hypercholesterolemia ( 24.4 vs. 30.8 % , P = 0.48 ) . However , there were a greater proportion of hypertensive patients in the diabetic group ( 63.8 vs. 39.7 % , P = 0.006 ) . Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee ( P = 0.02 ) . A greater number of amputations occurred in the diabetic group : diabetic patients were five times more likely to have an amputation ( 41.4 vs. 11.5 % , odds ratio [ OR ] 5.4 , P Mortality was higher in the diabetic group ( 51.7 vs. 25.6 % , OR 3.1 , P = 0.002 ) , and diabetic patients who died were younger at presentation than nondiabetic patients ( 64.7 + /- 11.4 vs. 71.1 + /- 8.7 years , P = 0.04 ) . CONCLUSIONS In patients with peripheral arterial disease , diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients", "BACKGROUND It is not clear whether subgroups of patients with peripheral artery disease ( PAD ) and claudication respond more favorably to exercise rehabilitation than others . We determined whether sex and diabetes were factors associated with the response to exercise rehabilitation in patients with claudication . METHODS Eighty patients were r and omized to home-based and supervised exercise programs , and 60 finished with complete exercise intervention data . Exercise consisted of intermittent walking to near maximal claudication pain for 3 months . Primary outcome measures included claudication onset time ( COT ) and peak walking time . Patients were partitioned into diabetic and nondiabetic groups and then further partitioned by sex to form four groups . RESULTS Overall , exercise adherence was high ( 84 % ) , and there was no significant difference ( P > .05 ) in the amount of exercise completed among the four groups . All groups had significant improvements ( P COT and peak walking time after exercise rehabilitation , except for diabetic women ( P > .05 ) . Only 37 % of women with diabetes had an increase in COT compared with 100 % of men with diabetes ( P Women with PAD and claudication , particularly those with diabetes , represent a vulnerable subgroup of patients who respond poorly to a program of exercise rehabilitation . Diabetic women with PAD and claudication may need a greater dose of exercise or another intervention separate from or in combination with exercise to elicit improvements in claudication measures that are similar to nondiabetic women and to diabetic and nondiabetic men" ]	41184960-06ff-11f0-808a-c43d1ab1c353
Abstract Background : Previous studies reported inconsistent findings regarding the effects of psyllium supplementation on obesity measures . This systematic review and meta- analysis was performed to summarize data from available r and omized clinical trials ( RCTs ) on the effect of psyllium supplementation on body weight , body mass index ( BMI ) , and waist circumference ( WC ) in adults . Methods : PubMed , SCOPUS , Cochrane Library , and Google Scholar were search ed to identify relevant articles up to August 2018 . The effect sizes were presented as weighted mean difference ( WMD ) and 95 % confidence intervals ( CI ) by using r and om effects model . To detect dose-response relationships , we used fractional polynomial modeling . Results : A total of 22 RCTs were included . Meta- analysis did not find any significant effect of psyllium supplementation on body weight ( MD : −0.28 kg , 95 % CI : −0.78 , 0.21 , p = 0.268 ) , BMI ( MD : −0.19 kg/m2 , 95 % CI : −0.55 , 0.15 , p = 0.27 ) and WC ( MD : −1.2 cm , 95 % CI : −2.6 , 0.2 , p = 0.09 ) . Subgroup analysis showed that psyllium dosage , kind of psyllium administration , duration of trial , study design , sample size , and gender were potential sources of heterogeneity . Moreover , there was nonlinear association between duration of psyllium consumption , BMI and WC . Conclusion : Psyllium supplementation does not reduce body weight , BMI , and WC significantly	[ "Fibres which are soluble or insoluble in water have different physiochemical properties and may therefore be expected to exert different effects on post-ingestive satiety signals . This study compared the effects on short-term ( 24 h ) appetite of two equienergetic high ( 22 g ) fibre breakfasts , an equienergetic low fibre breakfast and a low energy , ' light ' breakfast . Psyllium gum ( the soluble fibre ) and wheat bran ( the insoluble fibre ) were incorporated into breakfast cereals and consumed at breakfast by sixteen healthy , normal weight males after an overnight fast using a repeated measures , counterbalanced design . Ad libitum energy intake was assessed at a test snack 1.5 h after breakfast , later in the day using food boxes and the following day using food diaries . Motivation to eat and gastrointestinal sensations were tracked for the next 24 h. Hunger ratings showed a trend towards the subjects being less hungry and they consumed significantly less energy at snack time after the high insoluble than after the high soluble fibre breakfast cereal . The soluble fibre breakfast produced a greater suppression of snack intake than the light breakfast , but smaller suppression than the other breakfasts . Interestingly there was a trend toward reduced hunger and voluntary energy consumption following the soluble fibre compared with the insoluble fibre much later in the day ( 9.5 - 13.5 h after breakfast ) although this was not significant . There was no significant effect of breakfast type on total day energy intake . The results suggest that different types of fibre modulate the timecourse of appetite control and may produce alterations in the experience of motivation and patterns of eating without necessarily effecting total energy intake", "The effects of dietary fiber on subjective hunger ratings and weight losses were studied in 135 members of a weight loss club . After a run-in week , 100 members were r and omly given one sachet of either bran or ispaghula granulate before meals for two weeks . Thirty-five controls only rated hunger . One hundred and eight members completed the trial : 23 controls , 45 on ispaghula and 40 on bran . No change in hunger ratings was found in the controls . Both fiber preparations lowered hunger ratings during weeks 2 and 3 compared to the run-in week . Ratings were similarly reduced at all meals . The mean ( + /- SD ) weight reductions during the trial were 4.6 + /- 2.7 kg for the controls , 4.2 + /- 3.2 kg for the ispaghula group and 4.6 + /- 2.3 kg for the bran group ( p greater than 0.05 for all ) . In spite of recent changes in the diet towards food rich in dietary fibers , addition of extra dietary fiber immediately before meals reduced hunger feelings but had no effect on weight reduction", "BACKGROUND New dietary strategies to reduce cardiovascular disease ( CVD ) risk include the addition of fiber to the diet . The effect of soluble-fiber consumption derived from Plantago ovata husk on lipid risk factors in patients with CVD is unknown . OBJECTIVE We compared the effects of soluble fiber ( P. ovata husk ) with those of insoluble fiber ( P. ovata seeds ) on plasma lipid , lipoprotein , and apolipoprotein ( apo ) concentrations within a CVD secondary prevention program . DESIGN In a r and omized , crossover , controlled , single-blind design , 28 men with CVD ( myocardial infa rct ion or stable angina ) and an LDL-cholesterol concentration consumed for 8 wk , under controlled conditions , a low-saturated-fat diet supplemented with 10.5 g P. ovata husk/d or 10.5 g P. ovata seeds/d . Fasting plasma lipid concentrations and polymorphisms of genes involved in lipid metabolism , such as apo A-IV , apo E , and fatty acid-binding protein , were measured . RESULTS Plasma triacylglycerol decreased ( 6.7 % ; P ratio of apo B 100 to apo A-I decreased ( 4.7 % ; P apo A-I increased ( 4.3 % ; P P. ovata husk consumers . Compared with the intake of insoluble fiber , the intake of P. ovata husk increased HDL-cholesterol concentrations by 6.7 % ( P = 0.006 ) and decreased the ratio of total to HDL cholesterol and of LDL to HDL cholesterol by 10.6 % ( P = 0.002 ) and 14.2 % ( P = 0.003 ) , respectively . CONCLUSION In the secondary prevention of CVD , P. ovata husk intake induces a more beneficial effect on the cardiovascular lipid risk-factor profile than does an equivalent intake of insoluble fiber", "To determine whether psyllium must be mixed with food to lower serum cholesterol , 18 modestly hypercholesterolemic subjects were studied for three 2-wk periods , in r and om order , separated by a 2-wk return to a National Cholesterol Education Program Step 2 diet . Compared with values for subjects consuming control wheat-bran cereal ( 63 g/d ) , after 2 wk of 54 g psyllium-enriched cereal/d containing 7.3 g psyllium , serum total , LDL , and HDL cholesterol , respectively , were reduced by 8 % ( 6.15 + /- 0.15 vs 6.71 + /- 0.19 mmol/L , P psyllium as in the test cereal was taken between meals , serum total ( 6.50 + /- 0.19 mmol/L ) , LDL ( 4.50 + /- 0.21 mmol/L ) , and HDL ( 1.06 + /- 0.06 mmol/L ) cholesterol were no different from control values , and total cholesterol was greater than after psyllium cereal ( P psyllium must be mixed with foods to have the maximum effect on serum cholesterol", "BACKGROUND Cholecystokinin is associated with satiety . Fat stimulates cholecystokinin release , and fiber appears to prolong cholecystokinin elevation during the alimentary period . OBJECTIVE We tested whether adding fiber or fat to a low-fat , low-fiber meal increases cholecystokinin release and enhances subjective measures of satiety and whether the cholecystokinin response correlates with subjective measures of satiety . DESIGN Three isoenergetic breakfast meals were tested in a r and omized crossover design : low fiber , low fat ; high fiber , low fat ; and low fiber , high fat . Blood sample s were drawn from fasted subjects ( 7 men and 8 women ) before and at different time points after test meal consumption for 6 h. Plasma was analyzed for cholecystokinin , insulin , glucose , and triacylglycerols . Visual analogue scales were used to assess subjects ' hunger , desire to eat , fullness , and prospect i ve consumption . RESULTS In the women , the meals higher in fiber or in fat result ed in greater feelings of satiety and in significantly higher cholecystokinin responses than did the low-fat , low-fiber meal . In the men , the increase in cholecystokinin concentration did not differ between meals , but the 2 low-fat meals elicited a greater feeling of satiety than did the high-fat meal . The insulin response was significantly higher for the low-fiber , low-fat meal than for the other 2 meals , and the triacylglycerol response was greatest for the high-fat , low-fiber meal . CONCLUSION In women , the feeling of satiety caused by cholecystokinin release is enhanced by increasing either the fiber or fat content of a low-fat , low-fiber meal", "BACKGROUND Dietary fiber intake remains low despite increasing evidence for its health benefits , including laxation . OBJECTIVE We aim ed to assess the effects of increasing fiber intake on bowel habits and gastrointestinal tolerance in healthy persons consuming a typical Canadian or US diet . DESIGN Under a r and omized crossover design , 23 free-living participants consumed a typical Canadian or US diet ( 35 % fat , 12 g fiber/d ) and received 25.0 - 28.7 g fiber/d from each of 5 breakfast cereals : All-Bran ( AB ) , Bran Buds with Corn ( BBC ) , Bran Buds with Psyllium ( BBP ) , BBC with viscous fiber blend ( VFB ) , or a low-fiber control for 3 wk , with each study arm separated by a washout of > /=1 wk . Seven-day stool collection s and a symptom diary were obtained during the last week of each study arm . RESULTS All study cereals induced significant ( P fecal bulk from the control diet at 128 + /- 38 g to 199 + /- 56 , 199 + /- 57 , 247 + /- 87 , and 197 + /- 63 g with consumption of AB , BBC , BBP , and VFB , respectively ; less intestinal transit time ; and significantly ( P bowel movement frequency . Despite the increased activity of the bowel , a positive level of comfort was maintained . BBP was more effective than other cereals in terms of increasing fecal wet weight ( P < 0.05 ) . CONCLUSION Water-insoluble dietary fibers ( ie , AB and BBC ) and their mixtures with water-soluble fibers ( ie , BBP and VFB ) in the form of breakfast cereals ( 2.5 servings/d ) proved to be a practical way of increasing fiber intake to recommended levels , while maintaining a good level of tolerance", "Soluble-fiber breakfast cereals were examined for their cholesterol-lowering ability in 58 male patients with mild to moderate hypercholesterolemia in a r and omized , double-blind , placebo-controlled study . Patients followed a step 1 diet for a minimum of 6 wk , then were r and omly assigned to groups incorporating either corn flakes or one of two soluble-fiber cereals ( pectin enriched or psyllium enriched ) in the diet for an additional 6 wk . During the diet-only phase , total cholesterol dropped 3.8 % . During the cereal-plus-diet phase , total and LDL cholesterol values of the pectin-enriched cereal group dropped an additional 2.1 % ( P = 0.243 ) and 3.9 % ( P = 0.16 ) , respectively , and they dropped 5.9 % ( P = 0.005 ) and 5.7 % ( P = 0.034 ) , respectively , in the psyllium-enriched cereal group . During the cereal-plus-diet phase , no significant effects on HDL cholesterol , triglyceride , or body weight were found within or between any cereal groups . These results support use of soluble-fiber cereals as an effective and well-tolerated part of a prudent diet in the treatment of mild to moderate hypercholesterolemia", "The effects of consuming foods containing 0 ( control ) , 3.4 , 6.8 , or 10.2 g psyllium seed husk (PSH)/d for 24 wk on the serum lipid profile were assessed in this r and omized , double-blind controlled study . Men and women ( n = 286 ) with LDL-cholesterol concentrations between 3.36 and 5.68 mmol/L ( 130 and 220 mg/dL ) were r and omly assigned to one of four treatment groups after following a low-fat diet for > or = 8 wk . At week 24 , LDL cholesterol was 3 % above baseline in the control group . In the group consuming 10.2 g PSH/d , LDL cholesterol remained below baseline during treatment , with a value 5.3 % below that of the control group at week 24 ( P HDL cholesterol or triacylglycerol . Although modest , the effect of 10.2 g PSH/d on LDL cholesterol ( relative to the control ) persisted throughout the 24-wk treatment period , indicating potential for long-term benefit", "Background Water-soluble dietary fibers intake may help control blood glucose and body weight . Objective The objective of the study was to determine whether soluble fiber supplementation from psyllium improves glycemic control indicators and body weight in type 2 diabetic patients . Method Forty type 2 diabetes patients , non-smoker , aged > 35 years were stratified to different strata according to sex , age , body mass index ( BMI ) and fasting blood sugar level ( FBS ) and r and omly assigned into two groups ; The intervention group which consists of 20 participants was on soluble fiber ( 10.5 g daily ) , and the control group which consist of 20 participants continued on their regular diet for eight weeks duration . Results After 8 weeks of intervention , soluble fiber supplementation showed significant reduction in the intervention group in BMI ( p Moreover , water soluble fiber supplementation proven to improve FBS ( 163 to 119 mg/dl ) , HbA1c ( 8.5 to 7.5 % ) , insulin level ( 27.9 to 19.7 μIU/mL ) , C-peptide ( 5.8 to 3.8 ng/ml ) , HOMA.IR ( 11.3 to 5.8 ) and HOMA-β % ( 103 to 141 % ) . Conclusion The reduction in glycemic response was enhanced by combining soluble fiber to the normal diet . Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism and lipid profile in type 2 diabetes patients .Trial registration Current Controlled Trials PHRC/HC/28/15", "Dietary fiber ( DF ) and protein are essential constituents of a healthy diet and are well known for their high satiety impact . However , little is known about their influence on postpr and ial gastrointestinal ( GI ) peptide release . Our aim in this single-blind , r and omized , cross-over study was to investigate the effects of DF and /or protein enrichments on satiety-related metabolic and hormonal responses . Sixteen healthy , nonobese volunteers participated in the study and ingested 1 of 5 isoenergetic test meals in a r and omized order on separate days . The test meals were as follows : 1 ) low in protein ( 2.8 g ) and fiber ( 7.6 g ) ; 2 ) low in protein ( 2.6 g ) and high in soluble fiber ( psyllium , 23.0 g ) ; 3 ) high in protein ( soy , 19.7 g ) and low in fiber ( 6.2 g ) ; 4 ) high in protein ( 18.4 g ) and fiber ( 23.0 g ) ; and 5 ) white wheat bread . Serum insulin and plasma glucose , ghrelin , glucagon-like peptide 1 ( GLP-1 ) , and peptide YY ( PYY ) concentrations were determined for 2 h following the meals . In addition , hunger and satiety ratings were collected . Postpr and ial glucose , insulin , ghrelin , GLP-1 , and PYY responses all differed among the meals ( P glucose , insulin , ghrelin , and PYY responses ; in addition , PYY secretion was prolonged compared with the other meals . The postpr and ial GLP-1 concentration was significantly suppressed after a fiber- and protein-rich meal , in contrast to the initial increases following the other meals . However , postpr and ial ratings of appetite were mostly similar after the test meals . In conclusion , solid meals enriched with psyllium fiber strongly modified postpr and ial signals arising from the GI tract", "Background : Due to the attribution of fatty liver with some chronic diseases such as obesity , finding a way to control obesity can be useful for the management of fatty liver . This study was performed to assess the effects of Plantago psyllium ( PP ) and Ocimum basilicum ( OB ) on anthropometric measurements in people with hepatic steatosis . Methods : All patients with nonalcoholic fatty liver disease ( NAFLD ) were enrolled in this four-arm parallel , r and omized , and single blind trial . They r and omly assigned into four groups receiving ( 1 ) OB 10 g/day ; ( 2 ) PP 10 g/day ; ( 3 ) mix of OB and PP 10 g/day ; and ( 4 ) control group without placebo for 12 weeks . Anthropometric measurements were assessed during study baseline and after 12 weeks intervention . The data were analyzed using paired sample t-test for within group and analysis of covariance for between groups . Results : In within group analysis , weight and body mass index show a significant reduction after 12 weeks intervention . In addition , soft lean mass and lean body mass were decreased in PP and mixed of PP and OB groups significantly ; another group ( OB ) shows the same result for mass body fat . Although in intervention groups , we see considerable reduction , between group changes did not demonstrate the same consequences . Conclusions : The results of this study showed that administration of OB , PP , or mix of them for 12 weeks does not affect any of the anthropometric measures in NAFLD", "Hypercholesterolaemia is one of the major risk factors in the development of coronary artery disease . In recent years , many nonprescription treatments have become available for cholesterol lowering . Minolest is a product that contains guar gum and psyllium as the principal active ingredients . We conducted a r and omised , placebo-controlled , double-blind , parallel-group study to assess the efficacy of Minolest as a lipid-lowering agent . Secondary aims included assessment of the effect on blood pressure and obesity . We also looked at the acceptability of the product and side effects associated with its ingestion . After a 4-week run-in period , 83 subjects were r and omised to receive placebo or Minolest ( 16.5 g/day ) for 3 months . Seven subjects defaulted follow up , 5 in the placebo group and 2 in the active treatment group . In addition , 9 subjects ( 5 on active treatment and 4 on placebo ) had total cholesterol fall into the optimal range ( 5.2 mmol/l ) during the run-in phase and were removed from the study . At baseline in the active treatment group , total cholesterol was 6.1 ( 5.43 to 8.06 ) mmol/l , triglyceride 1.54 ( 0.56 to 4.19 ) mmol/l , HDL cholesterol 1.32 + /- 0.43 mmol/l and LDL cholesterol 4.1 ( 3.10 to 6.27 ) mmol/l . In the placebo group , total cholesterol was 5.84 ( 5.32 to 8.38 ) mmol/l , triglyceride 1.47 ( 0.69 to 11.0 ) mmol/l , HDL cholesterol 1.15 + /- 0.33 mmol/l and LDL cholesterol 3.87 ( 2.46 to 5.14 ) mmol/l . The differences in the baseline characteristics were not statistically significant except the LDL-cholesterol . Minolest produced a 3.24 % ( SD = 7.85 % , P = 0.020 ) decrease in total cholesterol and 5.45 % decrease in LDL cholesterol ( SD = 10.25 % , P = 0.0034 ) but no significant difference in serum triglyceride , weight , body mass index or blood pressure . This was not seen in the placebo group . The percentage fall in LDL cholesterol increased to 7.16 % and 7.37 % in subjects who consumed at least 50 % and 70 % of the treatment respectively . There were few side effects . The authors conclude that this product has a small impact on the lipid profile and may be useful only in subjects with mild hypercholesterolaemia and a low risk of coronary artery disease", "Background / Objectives Higher fibre intakes are associated with risk reduction for chronic diseases . However , many people find difficulty in consuming sufficient fibre through their diet . Supplements may be an effective alternative . We aim ed to investigate the effects of PolyGlycopleX ® ( PGX ® ) , a proprietary polysaccharide complex and a proprietary Psyllium product ( PgxSyl ™ ) ( PSY ) on diet , body weight and composition in overweight and obese individuals . Subjects/ Methods This was a double-blind 52 weeks study with 159 people r and omized to 3 groups : control ( rice flour ) ; PGX ( PGX ) and proprietary psyllium ( PSY ) . Participants did not change any of their usual habits or diet except they consumed 5 g of supplement taken with a total of 500 ml of water 5–10 min before meals . Results Weight was significantly lower in the PGX group compared to control at 3 ( −1.6 kg [ 0.57 , 2.67 , p = 0.003 ] ) , 6 ( −2.6 kg [ 1.01 , 4.13 , p = 0.001 ] ) and 12 months ( −2.6 kg [ 0.59 , 4.64 , p = 0.012 ] ) and in the PSY group compared to control group at 3 ( −1.1 kg [ 0.07 , 2.12 , p = 0.037 ] ) and 6 months ( −2.4 kg [ 0.95 , 3.93 , p = 0.002 ] ) . This was a difference of − 2.8 % for the PGX group and − 1.5 % for the PSY group compared to control after 12 months supplementation . Body Fat was significantly lower in PGX compared to control at 6 ( −1.8 kg [ 0.63 , 2.95 , p = 0.003 ] ) and 12 months ( −1.9 kg [ 0.43 , 3.36 , p = 0.012 ] ) and in PSY compared to control at 6 ( −1.9 kg [ 0.84 , 3.04 , p = 0.001 ] ) and 12 months ( −1.4 kg [ 0.08 , 2.71 , p = 0.038 ] ) . Conclusions PGX was better than PSY at maintaining dietary changes and weight loss over the 12 month intervention period , with no change to exercise . A simple strategy of PGX supplementation may offer an effective solution to long-term weight-loss and then management without the need for other nutrient modification . Trial registration ANZCTR : ACTRN12611000415909 . Registered 20 April", "The effect of psyllium hydrophilic mucilloid on serum cholesterol levels was investigated in 26 men with mild to moderate hypercholesterolemia ( range of cholesterol level , 4.86 to 8.12 mmol/L [ 188 to 314 mg/dL ] ) in a double-blind , placebo-controlled parallel study . Following a two-week baseline period , subjects were treated for eight weeks with 3.4 g of psyllium or cellulose placebo at mealtimes ( three doses per day ) . All subjects maintained their usual diets , which provided less than 300 mg of cholesterol per day and approximately 20 % of energy from protein , 40 % from carbohydrate , and 40 % from fat . Eight weeks of treatment with psyllium reduced serum total cholesterol levels by 14.8 % , low-density lipoprotein ( LDL ) cholesterol by 20.2 % , and the ratio of LDL cholesterol to high-density lipoprotein cholesterol by 14.8 % relative to baseline values . The reductions in total cholesterol and LDL cholesterol became progressively larger with time , and this trend appeared to be continuing at the eighth week . Psyllium treatment did not affect body weight , blood pressure , or serum levels of high-density lipoprotein cholesterol , triglycerides , glucose , iron , or zinc . No significant changes in serum lipid levels , body weight , blood pressure , or other serum parameters were observed with placebo treatment . Subject adherence to psyllium treatment was excellent , and no adverse effects were observed . Results of this study show that psyllium is an effective and well-tolerated therapy for mild to moderate hypercholesterolemia", "OBJECTIVES : This placebo-controlled open study was design ed to test the hypothesis that most of the gastrointestinal ( GI ) side events induced by treatment of obese patients with orlistat ( a gastrointestinal lipase inhibitor ) could be prevented or ameliorated by concomitant use of natural fibers ( psyllium mucilloid ) . DESIGN : Two groups of obese women ( BMI > 27 kg/m2 ) were treated with orlistat 120 mg three times a day . One group ( A , n=30 ) was r and omized to receive orlistat and , approximately 6.0 g of orange-flavored psyllium mucilloid dissolved in water and the other group ( B , n=30 ) received orlistat and orange-flavored placebo . At the end of 30 days and 2 weeks of washout , group A switched to placebo and group B received psyllium while continuing orlistat three times a day . SUBJECTS : Sixty professional women , more than 21-y-old with a body mass index ( BMI ) between 27.3 and 48.0 kg/m2 , who were not receiving any other medication . MEASUREMENTS : Assessment s included weekly visits to attending physician , filling a form in which GI events were recorded , monthly measurements of body weight , blood pressure and serum lipids . The frequency and severity of GI events were evaluated by a score system , based on information provided by the patients . RESULTS : Both groups A and B significantly lost ( P after 60 days of orlistat ( A=96.8 to 94.9 kg and B=98.7 to 96.5 kg ) . Similarly , BMI values declined significantly in both groups . While in the psyllium plus orlistat group ( group A ) the mean ±s.e.m . of the scores reflecting GI events was 13.0±1.8 , the placebo plus orlistat group ( B ) had a value of 35.9±2.7 ( P the placebo and orlistat group presented a mean score of 36.1±3.6 and the psyllium plus orlistat a mean score of 8.9±1.5 ( P obese patients receiving 120 mg of orlistat three times a day is an effective and safe adjunct therapy that is helpful in controlling the GI side effects of this pancreatic lipase inhibitor", "In the setting of a six-month , open-label clinical trial , 141 consecutively enrolled , hypertensive , overweight patients were r and omized to the oral ingestion of psyllium powder or guar gum 3.5 gr t.i.d . , to be taken 20 min before the main two meals , or to st and ard diet . Both fibers improved significantly BMI , FPG , FPI , HOMA Index , HbA1c , LDL-C , and ApoB. Psyllium supplementation only exerted a significant improvement in plasma TG concentration , in SBP and DBP . In our study , six-month supplementation with psyllium fiber , but not with guar fiber nor st and ard diet , appears to significantly reduce both SBP and DBP in hypertensive overweight subjects", "The beneficial effect of dietary fiber in the management of type II diabetes is still controversial and has not been totally demonstrated . The purpose of this study was to determine the plasma-lowering effects of 5 g t.i.d . of Plantago Psyllium , as an adjunct to dietary therapy , on lipid and glucose levels , in patients with type II diabetes . Patients were r and omly selected from an outpatient clinic of primary care to participate in a double-blind placebo-controlled study in which Plantago Psyllium or placebo was given in combination with a low fat diet . One hundred twenty-five subjects were included in the study that consisted in a 6-week period of diet counseling followed by a 6-week treatment period . Fasting plasma glucose , total plasma cholesterol , LDL cholesterol , HDL cholesterol and triglyceride levels were measured every 2 weeks . The test products ( Psyllium or placebo ) were supplied to subjects in identically labeled foil packets containing a 5-g dose of product , to consume three doses per day ( of 5 g each one ) , before regular meals . There was an excellent tolerance to Psyllium , without significant adverse effects . No significant changes were observed in the patient 's weight for both groups ( not significant ) . Fasting plasma glucose , total cholesterol , LDL cholesterol , and triglycerides levels , showed a significant reduction ( p HDL cholesterol increased significantly ( p Psyllium is useful , as an adjunct to dietary therapy , in patients with type II diabetes , to reduce plasma lipid and glucose levels , resolving the compliance conflict associated with the ingest of a great amount of fiber in customary diet", "BACKGROUND Psyllium and oat bran have been shown to lower plasma LDL cholesterol levels in different population s. Hypercholesterolemia is prevalent in the Northern part of Mexico and might be associated to dietary habits and sedentary lifestyle . METHODS Sedentary normal ( cholesterol220 mg/dL ) ( n=30 ) men from the Northern part of Mexico aged 20 to 45 years of age participated in an 8-week study to determine the effects of dietary soluble fiber , either psyllium or oat bran , in lowering plasma LDL cholesterol in this population . Fiber was administered by feeding the subjects an amount of cookies ( 100 g ) equivalent to 1.3 or 2.6 g/day of soluble fiber from psyllium or oat bran , respectively . Subjects were r and omly allocated to three groups : a control group consuming cookies with wheat bran , a known source of fiber with no cholesterol lowering effects , psyllium , or oat bran . RESULTS Food frequency question naires indicated that subjects from the three groups had similar intakes of foods classified as hypercholesterolemic ( p>0.05 ) . Plasma LDL cholesterol concentrations were reduced by an average of 22.6 and 26 % in the psyllium and oat bran groups ( p plasma HDL or triglycerides levels were observed among the three dietary treatments except for hypercholesterolemic individuals supplemented with oat bran where a 28 % reduction in plasma triglycerides was observed after 8 weeks ( p psyllium and oat bran are efficacious in lowering plasma LDL cholesterol in both normal and hypercholesterolemic individuals from this population", "Psyllium is a bulk-forming laxative and is high in both fiber and mucilage . The beneficial effect of dietary fiber in the management of type II diabetes , has not been totally demonstrated . The purpose of this study was to determine the plasma-lowering effects of 5.1 g b.i.d . of psyllium husk fiber , as an adjunct to dietary and drug therapy on lipid and glucose levels , in patients with type II diabetes . Patients were r and omly selected from an outpatient clinic of primary care to participate in a double-blind placebo-controlled study in which Plantago ovata Forsk . , or placebo was given in combination with their anti-diabetic drugs . Forty-nine subjects were included in the study that were given diet counseling before the study and then followed for 8 weeks in the treatment period . Fasting plasma glucose ( FBS ) was measured every 2 weeks , and total plasma cholesterol ( TC ) , LDL-cholesterol ( LDL-C ) , HDL-cholesterol ( HDL-C ) , triglyceride ( TG ) , and insulin levels were measured every 4 weeks . Glycosylated hemoglobin ( HbA1c ) was also measured at the beginning and ending of the study . The test products ( psyllium or placebo ) were supplied to subjects in identically labeled foil packets containing a 5.1 g dose of product , to consume two doses per day , half an hour before breakfast and dinner . Both products were well tolerated , with no serious adverse events related to treatment was reported in either . Better gastric tolerance to metformin was recorded in the psyllium group . FBS , and HbA1c , showed a significant reduction ( p HDL-C increased significantly ( p LDL/HDL ratio was significantly decreased ( p psyllium for persons with type II diabetes is safe , well tolerated , and improves glycemic control", "This study provides preliminary data on the influence of ingestion of 15 g of dietary fiber daily for 4 weeks on weight change and serum iron concentrations in obese children . During two consecutive 4-week periods , subjects received either fiber/placebo supplements or placebo/fiber supplements . Initially , and after the fourth and eighth weeks , height , weight , and serum iron concentration were obtained . Diet records were maintained throughout the study . No significant differences ( p less than or equal to 0.05 ) were found in weight change , energy , iron , and crude fiber intakes and serum iron concentrations of the subjects between periods of fiber and placebo supplementation . However , mean weight loss of subjects ( 336 g ) was greater during fiber ingestion than during placebo ingestion ( 33 g ) . Due to the small sample size and the subjects ' poor compliance , further studies are needed , with a larger sample size , to determine the effectiveness of different fibers in the treatment of obesity", "BACKGROUND Dietary fiber may play a role in obesity prevention . Until now , the role that fiber from different sources plays in weight change had rarely been studied . OBJECTIVE Our aim was to investigate the association of total dietary fiber , cereal fiber , and fruit and vegetable fiber with changes in weight and waist circumference . DESIGN We conducted a prospect i ve cohort study with 89,432 European participants , aged 20 - 78 y , who were free of cancer , cardiovascular disease , and diabetes at baseline and who were followed for an average of 6.5 y. Dietary information was collected by using vali date d country-specific food-frequency question naires . Multiple linear regression analysis was performed in each center studied , and estimates were combined by using r and om-effects meta-analyses . Adjustments were made for follow-up duration , other dietary variables , and baseline anthropometric , demographic , and lifestyle factors . RESULTS Total fiber was inversely associated with subsequent weight and waist circumference change . For a 10-g/d higher total fiber intake , the pooled estimate was -39 g/y ( 95 % CI : -71 , -7 g/y ) for weight change and -0.08 cm/y ( 95 % CI : -0.11 , -0.05 cm/y ) for waist circumference change . A 10-g/d higher fiber intake from cereals was associated with -77 g/y ( 95 % CI : -127 , -26 g/y ) weight change and -0.10 cm/y ( 95 % CI : -0.18 , -0.02 cm/y ) waist circumference change . Fruit and vegetable fiber was not associated with weight change but had a similar association with waist circumference change when compared with intake of total dietary fiber and cereal fiber . CONCLUSION Our finding may support a beneficial role of higher intake of dietary fiber , especially cereal fiber , in prevention of body-weight and waist circumference gain", "UNLABELLED The objective was to evaluate whether the soluble fibre Plantago ovata (Po)-husk improves cardiovascular disease ( CVD ) risk biomarkers including low-density lipoprotein cholesterol ( LDL-C ) . METHODS In a multi-centred , double-blind , placebo-controlled , parallel , r and omised trial conducted in primary care-clinics in Spain , France and Holl and , mild-moderate hypercholesterolaemic patients ( age range : 43 - 67 years ) received 14 g/d of Po-husk ( n=126 ) or placebo ( microcrystalline-cellulose 14 g/d ; n=128 ) in a low saturated fat diet for 8 weeks . Subsequently , if LDL-C remained > or = 3.35 mmol/L [ 130 mg/dL ] , participants proceeded with the fibre plus simvastatin ( 20mg/d ) for further 8 weeks . Lipid profile , blood pressure ( BP ) , insulin , oxidised LDL and some gene polymorphisms involved in CVD risk were measured . RESULTS Relative to placebo , Po-husk reduced plasma LDL-C by -6 % ( P total cholesterol ( TC ) by -6 % , triglycerides ( TG ) by -21.6 % , apolipoprotein ( Apo ) B-100 by -6.7 % , oxidised LDL by a mean of -6.82 U/L ( 95%CI : 3.15 - 10.48 ) , insulin by -4.68 pmol/L ( 95%CI : 0.68 - 8.67 ) and systolic BP by -4.0 mm Hg ( 95%CI ; 1.2 - 6.7 ) ( P TG-lowering effect in the Po-husk group was magnified by variants in plasminogen-activator-inhibitor ( PAI-1 ; rs1799768 ) and fatty acid-binding protein ( FABP-2 ; rs1799883 ) genes . At 16 weeks , the intra-group action of simvastatin ( 20mg/d ) added to Po-husk or placebo was a similar LDL-C reduction . CONCLUSIONS Po-husk , apart from lowering LDL-C , also reduced TG , TG related to certain gene variants , TC , Apo B-100 , oxLDL , insulin-resistance and systolic BP in mild-moderate hypercholesterolaemic individuals . Thus , the target patients to receive Po-husk would be those who present a cluster of various CVD risk factors , such as metabolic syndrome", "The effect of plasma glucose on satiety and the capacity of carbohydrates to stimulate cholecystokinin ( CCK ) remain unclear . The aim of this study was to test the hypothesis that the magnitude of the postpr and ial plasma glucose and insulin response is inversely related to the CCK response and to subjective satiety . Seven healthy , male volunteers consumed equal carbohydrate portions ( 0.5 g/kg body weight ) of six test meals ( Rice Bubbles , Sustain , Vita-Brits , All-Bran , porridge and white bread ) in r and om order after an overnight fast . An egg and bacon meal was consumed as a non-carbohydrate control providing 0.5 g protein/kg body weight . Serum CCK , plasma glucose and insulin and subjective satiety ( measured by a rating scale ) were assessed over 3 h and quantified using the glycaemic index ( GI ) , insulin index ( II ) , the peak satiety score and area under the incremental curve ( AUC ) . The observed GIs ( mean + /- SE ) ranged from 42.5 + /- 2.6 for All-Bran to 116.2 + /- 11.4 for Rice Bubbles , using white bread as the reference food ( GI = 100 ) . Peak satiety scores varied eightfold from 0.21 + /- 0.4 for Sustain to 1.64 + /- 0.4 for All-Bran . Significant inverse relationships were observed between the peak satiety score and both the glycaemic and insulin index of the seven meals ( r = -0.916 , p less than 0.001 and r = -0.926 , p less than 0.001 ) . A direct relationship was observed between satiety ( AUC ) and the CCK response ( AUC ) ( r = 0.73 p less than 0.01 ) . The results suggest that glycaemic and insulin responses to carbohydrate foods are inversely proportional to the CCK response and satiety", "OBJECTIVE To compare the effects of baked psyllium supplementation versus those who received a placebo on constipation symptoms , body weight , glycemic and lipids control in patients with type 2 diabetes ( T2D ) and chronic constipation . METHODS In a single-blinded , r and omized controlled trial , 51 patients with T2D and chronic constipation with body mass index ( BMI ) 20 - 47 kg/m2 received either 10 g of psyllium pre-mixed in cookies twice per day or placebo cookies for 12 weeks . Constipation symptoms , body mass index ( BMI ) , fasting plasma glucose ( FPG ) , glycosylated hemoglobin ( HbA1c ) , and lipid profile were determined at the beginning and end of 4 , 8 , and 12-week period . Constipation was evaluated with a stool diary ( ROME III ) . RESULTS The psyllium group showed improvement in constipation symptoms , body weight , glucose and lipid values compared with the baseline and the placebo group . Body weight and FPG decreased from baseline in the psyllium group ( P change of body weight ( -2.0 ( -3.0 , -1.0 ) kg ; P FPG ( -13.6 ( -24.3 , -2.9 ) mg/dl ; P = .040 ) , and HbA1c ( -1.7 ( -2.9 , -0.5 ) ) ; P = 0.002 ) between the groups were statistically significant . Cholesterol ( -21.5 ( -25.6 , -14.4 ) ; P triglycerides ( -20.0 ( -32.3 , -7.7 ) ; P = 0.021 ) and constipation symptoms ( 1.5 ( 0.4 , 2.3 ) ; P psyllium group . The compliance was good and no adverse effects were observed . CONCLUSION In patients with T2D and chronic constipation , psyllium supplementation decreased constipation symptoms , body weight , glycemic , cholesterol , and increased HDLC levels" ]	411849e2-06ff-11f0-808a-c43d1ab1c353
Aim To develop a scientifically current and evidence based protocol on the efficacy of rotary and h and root canal instrumentation in primary teeth . Material s and methods Previous r and omized control trials were used for the current review . H and search and online search engines of PUBMED and Google Scholar were used to search English language articles with human subjects published up to December 2016 . Results After screening of the abstract s and articles , based on the inclusion and exclusion criteria a total of 13 articles were included in the systematic review . Conclusion Rotary instrumentation shows equivalent cleaning efficiency than h and files depending on the system of instrumentation and techniques used . However , use of rotary in primary teeth leads to improved shaping of canals providing better quality of treatment in less time . How to cite this article Panchal V , Jeevan and an G , et al. Comparison between the Effectiveness of Rotary and Manual Instrumentation in Primary Teeth : A Systematic Review . Int J Clin Pediatr Dent 2019;12(4):340 - 346	[ "INTRODUCTION : Pulpectomy of primary teeth is commonly carried out with h and files and broaches ; a tricky and time consuming procedure . The purpose of this in vitro study was to compare the cleaning efficacy and time taken for instrumentation of deciduous molars using h and K-files and Flex Master rotary system . MATERIAL S AND METHODS : In this study , 68 canals of 23 extracted primary molars with at least two third intact roots and 7 - 12 mm length were selected . After preparing an access cavity , K-file size # 15 was introduced into the root canal and India ink was injected with an insulin syringe . Sixty sample s were r and omly divided in to experimental groups in group I ( n=30 ) , root canals were prepared with h and K-files ; in group II ( n=30 ) , rotary Flex Master files were used for instrumentation , and in group III 8 remained sample s were considered as negative controls . After clearing and root sectioning , the removal of India ink from cervical , middle , and apical thirds was scored . Data was analyzed using student 's T-test and Mann-Whitney U test . RESULTS : There was no significant difference between experimental groups cleaning efficacy at the cervical , middle and apical root canal thirds . Only the coronal third scored higher in the h and instrumented group ( P Flex Master rotary files was significantly less time consuming ( P cleanliness efficacy at the apical and middle thirds , the coronal third was more effectively cleaned with h and files . Predictably , time efficiency was a significant advantage with rotary technique", "Background : Root canal cleaning is an important step in endodontic therapy . In order to develop better techniques , a new generation of endodontic instruments has been design ed . The aim of this study was to compare the effectiveness of manual K-files ( Mani Co , Tokyo , Japan ) and two rotary systems – Mtwo ( Dentsply-Maillefer , Ballaigues , Switzerl and ) and ProTaper ( VDW , Munich , Germany)–for root canal preparation in primary molars . Material s and Methods : India ink was injected to 160 mesiobuccal and distal root canals of m and ibular primary molars . The teeth were r and omly divided into three experimental groups and one control group . In each experimental group , either manual instruments ( K-files ) or rotary instruments ( Mtwo or ProTaper ) were used to prepare root canals . After cleaning the canals and clearing the teeth , ink removal was evaluated with a stereomicroscope . Statistical analysis was done with Kruskal – Wallis and Friedman tests . Results : There were no significant differences in cleaning efficiency between manual and rotary instruments . Only ProTaper files performed significantly better in the coronal and middle thirds than in the apical third of the root canal . Conclusion : Manual K-files and the Mtwo and ProTaper rotary systems showed equally acceptable cleaning ability in primary molar root canals ", "Background . Efficient canal preparation is the key to successful root canal treatment . This study aim ed to assess the cleaning and shaping ability , preparation time and file deformation of rotary , reciprocating and manual instrumentation in canal preparation of primary molars . Methods . The mesiobuccal canals of 64 extracted primary m and ibular second molars were injected with India ink . The sample s were r and omly divided into one control and three experimental groups . Experimental groups were instrumented with K-file , Mtwo in continuous rotation and Reciproc in reciprocating motion , respectively . The control group received no treatment . The files were discarded after four applications . Shaping ability was evaluated using CBCT . After clearing , ink removal was scored . Preparation time and file fracture or deformation was also recorded . Data were analyzed with SPSS 19 using chi-squared , Fisher ’s exact test , Kruskal-Wallis and post hoc tests at a significance level of 0.05 . Results . Considering cleanliness , at coronal third Reciproc was better than K-file ( P canal cleaner than K-file ( P = 0.001 ) . In the middle third , only Reciproc exhibited better cleaning efficacy than K-file ( P = 0.005 ) . In the apical third , no difference was detected between the groups ( P = 0.794 ) . Regarding shaping ability , no differences were found between Reciproc and Mtwo ( P = 1.00 ) . Meanwhile , both displayed better shaping efficacy than K-file ( P preparation time ( P file failure occurred . Conclusion . Fast and sufficient cleaning and shaping could be achieved with Mtwo and especially with Reciproc", " OBJECTIVES The aims of this study were to evaluate iodoform base material s for root canal treatment of necrotic primary teeth , and to compare them with traditionally used zinc oxide and eugenol ( ZOE ) . SAMPLE AND METHODS Zinc oxide and eugenol and Vitapex ( a premixed calcium hydroxide and iodoform paste ) were compared for root canal treatment in 52 necrotic primary teeth in two groups of children with a mean age of 5 years and 8.4 months . All the patients were followed-up clinical ly and radiographically 3 months and 10 - 16 months postoperatively . RESULTS The overall success rates of Vitapex and ZOE were 100 % and 78.5 % , respectively . Using Fisher 's Exact Test , the difference was statistically significant ( P ZOE and Vitapex gave encouraging results . Vitapex , however , can be used more safely whenever there is a doubt about the patient 's return for follow-up", "AIM To compare and evaluate the volumetric analysis of pre- and post-root canal instrumentation in primary teeth using h and and rotary files and also to analyse the volume of root canal filling . MATERIAL S AND METHODS A total of 20 primary teeth were divided into two groups r and omly and subjected to spiral computed tomography ( SCT ) analysis before and after instrumentation . For manual technique ( Group 1 ) , teeth were prepared using K files and rotary ( Group 2 ) preparation was performed with Mtwo files . Volumetric enlargement was calculated using Osirix software . Root canals were then filled with rotary lentulospiral using zinc oxide-eugenol cement ( ZOE ) . The filled volume in each canal was measured using SCT and the percentage of obturated volume was calculated . The data were statistically analysed using paired t-tests . RESULTS There was a statistically significant difference in the volume of root canal enlarged in both the groups . Rotary files showed significant increase in the volume compared to K files . Mtwo instrumented root canals showed good obturated volume compared to manual technique , although voids were common in both the groups . CONCLUSION Rotary root canal instrumentation may be indicated for utilization in primary teeth , for enhancing root canal preparation and good quality of root canal filling" ]	41184a5a-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To assess whether progesterone ( P4 ) or osteoblast P4 receptor-acting progestin ( P ) contributed to estrogen ( E ) therapy-related increased areal bone mineral density ( BMD ) in r and omized controlled trials ( RCT ) with direct r and omization to estrogen ( ET ) or estrogen-progestin ( EPT ) therapy . METHODS Systematic literature search es in biomedical data bases identified RCT with direct r and omization and parallel estrogen doses that measured spinal BMD change/year . Cyclic P4/P was included in this r and om effects meta- analysis only if for ≥ half the number of E-days . RESULTS Search es yielded 155 publications ; five met inclusion criteria providing eight dose-parallel ET-EPT comparisons in 1058 women . Women averaged mid-50 years , ⟨five years into menopause and took conjugated equine E daily at 0.625 mg with/without 2.5 mg medroxyprogesterone acetate ( MPA ) . The weighted mean EPT minus ET percentage difference in spinal BMD change was + 0.68%/year ( 95 % CI 0.38 , 0.97 % ) ( P=0.00001 ) . This result was highly heterogeneous ( I²=81 % ) but this may reflect the small number of studies . CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET . These data have implication s for management of vasomotor symptoms and potentially for osteoporosis treatment in menopausal women	[ "Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone ( PTH ) may blunt the anabolic effect of PTH ; rodent models suggest that infrequently administered bisphosphonates may interact differently . To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1 - 34 ) ( teriparatide ) 20 µg versus either agent alone on bone mineral density ( BMD ) and bone turnover markers , we conducted a 1-year multicenter , multinational , r and omized , partial double-blinded , controlled trial . 412 postmenopausal women with osteoporosis ( mean age 65 ± 9 years ) were r and omized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg ( n = 137 ) , zoledronic acid alone ( n = 137 ) , or teriparatide alone ( n = 138 ) . The primary endpoint was percentage increase in lumbar spine BMD ( assessed by dual-energy X-ray absorptiometry [ DXA ] ) at 52 weeks versus baseline . Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip , trochanter , and femoral neck at all time points . At week 52 , lumbar spine BMD had increased 7.5 % , 7.0 % , and 4.4 % in the combination , teriparatide , and zoledronic acid groups , respectively ( p and teriparatide versus zoledronic acid ) . In the combination group , spine BMD increased more rapidly than with either agent alone ( p both teriparatide and zoledronic acid at 13 and 26 weeks ) . Combination therapy increased total-hip BMD more than teriparatide alone at all times ( all p than zoledronic acid at 13 weeks ( p the combination , teriparatide , and zoledronic acid groups , respectively . With combination therapy , bone formation ( assessed by serum N-terminal propeptide of type I collagen [ PINP ] ) increased from 0 to 4 weeks , declined minimally from 4 to 8 weeks , and then rose throughout the trial , with levels above baseline from 6 to 12 months . Bone resorption ( assessed by serum β-C-telopeptide of type I collagen [ β-CTX ] ) was markedly reduced with combination therapy from 0 to 8 weeks ( a reduction of similar magnitude to that seen with zoledronic acid alone ) , followed by a gradual increase after week 8 , with levels remaining above baseline for the latter half of the year . Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p BMD ( e.g. , quantitative computed tomography and finite-element modeling for bone strength ) , lack of teriparatide placebo , and insufficient power for fracture outcomes . We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide , combination therapy provides the largest , most rapid increments when both spine and hip sites are considered", "OBJECTIVE To report the histological findings of the endometrium of postmenopausal women who were r and omized to receive placebo , estrogen only , or one of three estrogen plus progestin ( E+P ) regimens in the Postmenopausal Estrogen/Progestin Interventions ( PEPI ) Trial . DESIGN A 3-year multicenter , r and omized , double-masked , placebo-controlled trial . PARTICIPANTS A total of 596 postmenopausal women aged 45 through 64 years without contraindication to hormone therapy . INTERVENTION Participants were r and omized and stratified in equal numbers to one of the following treatments in 28-day cycles : placebo , 0.625 mg/d of conjugated equine estrogens ( CEE ) , 0.625 mg/d of CEE plus 10 mg/d of medroxyprogesterone acetate ( MPA ) for the first 12 days , 0.625 mg/d of CEE plus 2.5 mg/d of MPA , or 0.625 mg/d of CEE plus 200 mg/d of micronized progesterone ( MP ) for the first 12 days . OUTCOME MEASURE Histology of endometrium collected at baseline , annual , or unscheduled visits by biopsy , curettage , or hysterectomy . ANALYSIS Intention to treat . RESULTS During follow-up women assigned to estrogen alone were more likely to develop simple ( cystic ) , complex ( adenomatous ) , or atypical hyperplasia than those given placebo ( 27.7 % vs 0.8 % , 22.7 % vs 0.8 % , and 11.8 % vs 0 % , respectively ) for the same types of hyperplasia ( P E+P regimens had similar rates of hyperplasia as those given placebo ( P = .16 ) . The occurrence of hyperplasia was distributed evenly across the 3 years of the trial . Women taking estrogens alone also had more unscheduled biopsies ( 66.4 % vs 8.4 % ; P curettages ( 17.6 % vs 0.8 % ; P . The number of surgical procedures was similar for women receiving placebo and women receiving the E+P regimens ( P = .38 ) . Of the 45 women with complex ( adenomatous ) or atypical hyperplasia , study medications were discontinued in all , and the biopsy results of 34 ( 94 % ) of 36 women with hyperplasia reverted to normal with progestin therapy . The remainder had dilatation and curettage ( n = 2 ) or hysterectomy with ( n = 2 ) or without ( n = 6 ) prior medical therapy , or refused further biopsies ( n = 1 ) . One woman developed adenocarcinoma of the endometrium while receiving placebo . CONCLUSIONS At a dosage of 0.625 mg , the daily administration of CEE enhanced the development of endometrial hyperplasia . Combining CEE with cyclic or continuous MPA or cyclic MP protected the endometrium from hyperplastic changes associated with estrogen-only therapy", "The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy . This 1-year double-blind r and omized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals . Premenopausal women 45 + /- 5 years old , postovariectomy for benign diseases were provided 600 mg/day of calcium and r and omized to daily therapy with conjugated equine estrogen ( CEE , 0.6 mg ) or medroxyprogesterone ( MPA , 10 mg ) . The primary outcome variable was spinal quantitative computed tomography ( QCT ) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry ( DXA ) of proximal femur ( FN ) , whole body ( WB ) , and spine segment ( WBS ) and N-telopeptide , bone-specific alkaline phosphatase , and other bone marker , hormonal , and weight changes . Results in the 33 women completing the study , whose initial bone densities were normal ( QCT 133 mg/cm3 , femoral neck 0.94 g/cm2 , whole body DXA 1.13 g/cm2 ) , showed annual QCT loss during CEE therapy of -11.5 mg/cm3 ( p MPA bone loss of -19.7 mg/cm3 ( p Losses were marginally greater on MPA than CEE ( p = 0.04 ) . Extremely high postovariectomy ( 5 days ) and pretreatment resorption markers ( > 3 SD above premenopausal normal levels ) were significantly related to bone loss . Across the year , resorption decreased during CEE but increased on MPA treatment . Significant DXA bone losses were prevented by CEE treatment ( -1.4 % FN , -.4 % WB , and -1.5 % WBS , all NS ) . However , DXA bone loss was not prevented by MPA treatment ( -5 % FN , -2.8 % WB , and -6.1 % WBS , all p Average weight gain was significant ( + 3.2 + /- 4.0 kg ) and greater on CEE than MPA ( + 4.7 vs. + 2.0 kg , p = 0.049 ) . In conclusion , CEE therapy did not prevent significant 8 % cancellous spinal bone loss in the first year following premenopausal ovariectomy , despite supplementation with 600 mg/day of calcium , good control of vasomotor symptoms , and nearly 5 kg of gain in weight . Significant DXA bone loss , however , was prevented by CEE , but not by MPA therapy . These unexpected results were statistically related to high bone resorption following ovariectomy , which CEE suppressed but MPA did not . Bone formation markers increased during MPA therapy but were unchanged during CEE therapy", "Oestrogen therapy is the gold st and ard treatment for hot flushes/night sweats , but it and oestrogen/progestin are not suitable for all women . MPA ( medroxyprogesterone acetate ) reduces hot flushes , but its effectiveness compared with oestrogen is unknown . In the present study , oral oestrogen [ CEE ( conjugated equine oestrogen ) ] and MPA were compared for their effects on hot flushes in a planned analysis of a secondary outcome for a 1-year r and omized double-blind parallel group controlled trial in an urban academic medical centre . Participants were healthy menstruating women prior to hysterectomy/ovariectomy for benign disease . A total of 41 women { age , 45 ( 5 ) years [ value is mean ( S.D. ) ] } were enrolled ; 38 women were included in this analysis of daily identical capsules containing CEE ( 0.6 mg/day ) or MPA ( 10 mg/day ) . Demographic variables did not differ at baseline . Daily data provided the number of night and day flushes compared by group . The vasomotor symptom day-to-day intensity change was assessed by therapy assignment . Hot flushes/night sweats were well controlled in both groups , one occurred on average every third day and every fourth night . Mean/day daytime occurrences were 0.363 and 0.187 with CEE and MPA respectively , but were not significantly different ( P=0.156 ) . Night sweats also did not differ significantly ( P=0.766 ) . Therapies were statistically equivalent ( within one event/24 h ) in the control of vasomotor symptoms . Day-to-day hot flush intensity decreased with MPA and tended to remain stable with CEE ( P CEE are equivalent and effective in the control of the number of hot flushes/night sweats immediately following premenopausal ovariectomy", "Background Progesterone is effective treatment for hot flushes/night sweats . The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection . We compared the effects of progesterone to placebo on endothelial function , weight , blood pressure , metabolism , lipids , inflammation and coagulation . Methods and Results We conducted a r and omized , double-blind , 3-month placebo-controlled trial of progesterone ( 300 mg daily ) among 133 healthy postmenopausal women in Vancouver , Canada from 2003–2009 . Endothelial function by venous occlusion plethysmography was a planned primary outcome . Enrolled women were 1–11 y since last menstruation , not using hormones ( for > 6 months ) , non-smoking , without diabetes , hypertension , heart disease or their medications . R and omized ( 1∶1 ) women ( 55±4 years , body mass index 25±3 ) initially had normal blood pressure , fasting lipid , glucose and electrocardiogram results . Endothelial function ( % forearm blood flow above saline ) was not changed with progesterone ( 487±189 % , n = 18 ) compared with placebo ( 408±278 % , n = 16 ) ( 95 % CI diff [ −74 to 232 ] , P = 0.30 ) . Progesterone ( n = 65 ) and placebo ( n = 47 ) groups had similar changes in systolic and diastolic blood pressure , resting heart rate , weight , body mass index , waist circumference , total cholesterol , low-density lipoprotein cholesterol and triglyceride levels . High-density lipoprotein was lower ( −0.14 mmol/L , P = 0.001 ) on progesterone compared with placebo . Fasting glucose , hs-C-reactive protein , albumin and D-dimer changes were all comparable to placebo . Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo . Conclusions Results indicate that progesterone has short-term cardiovascular safety . Endothelial function , weight , blood pressure , waist circumference , inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinical ly important ( based on lack of Cardiovascular Risk Profile change ) . Trial Registration Clinical Trials.gov", "PURPOSE To determine the effect of progestin therapy on bone mineral density in postmenopausal women and to compare its effects to those of estrogen . SUBJECTS AND METHODS A prospect i ve , r and omized clinical trial was performed in 81 postmenopausal women aged 51.7 + /- 4.4 years ( mean + /- SD ) . They were assigned to one of four groups : Provera 20 mg , Premarin 0.6 mg , Premarin 0.3 mg plus Provera 10 mg , and a placebo . In addition , all women received calcium supplementation , if necessary , to a calcium intake of 1,000 mg/day . We used single- and dual-photon absorpiometry , metacarpal radiogrammetry , and computed axial tomography to measure bone mineral density in the total skeleton , spine , radius , and metacarpal . RESULTS Women receiving placebo lost bone at all sites ( p less than 0.01 ) . The Provera-treated group showed no change in total body calcium , but there were decreases in radial density ( p less than 0.01 ) , metacarpal cortex ( p less than 0.01 ) , and spine density ( p less than 0.01 ) . The Premarin-treated group had an increase in spine density and total body density ( p less than 0.05 ) , but a decrease in radial density ( p less than 0.05 ) . The Premarin-plus-Provera group showed no change in spine density , total body calcium , or radial density but had a decrease in metacarpal cortex ( p less than 0.01 ) . CONCLUSIONS Compared to placebo , Provera reduced the rate of loss in cortical areas of the skeleton , but not in the spine , which contains more trabecular bone . In contrast , Premarin reduced the rate of loss in both cortical and trabecular areas of the skeleton . The low-dose combination of Premarin plus Provera was similar in its effect on bone to that of Premarin alone , suggesting that there may be a synergistic effect of this hormone combination on bone . Serum cholesterol levels decreased with Provera , Premarin , and the combination of both , whereas levels of serum triglycerides increased with Premarin treatment , decreased with the Provera regimen , and were unchanged with the combination therapy . Provera does not adversely affect the lipid profile", "The value of oestrogen therapy in the prevention of osteoporosis after oophorectomy was assessed in 114 middle-aged women who participated in a double-blind controlled trial of mestranol in an average daily dose of 23 mug . The skeletal response to treatment was measured by a photon absorption technique . Where treatment was started within two months of operation subsequent bone mineral loss was prevented . Treatment started three years after oophorectomy caused a highly significant increase in bone mineral content . When treatment was delayed for six years mestranol failed to prevent subsequent bone mineral loss with age . These effects occurred independently of the associated humoral changes in calcium and phosphorus homoeostasis . Mestranol in this dosage appeared to be relatively safe , but it is too early to evaluate the long-term hazards of such therapy", "Teriparatide ( rDNA origin ) injection [ recombinant human PTH ( 1 - 34 ) ] stimulates bone formation , increases bone mineral density ( BMD ) , and restores bone architecture and integrity . In contrast , bisphosphonates reduce bone resorption and increase BMD . We compared the effects of teriparatide and alendronate sodium on BMD , nonvertebral fracture incidence , and bone turnover in 146 postmenopausal women with osteoporosis . Women were r and omized to either once-daily sc injections of teriparatide 40 micro g plus oral placebo ( n = 73 ) or oral alendronate 10 mg plus placebo injection ( n = 73 ) . Median duration of treatment was 14 months . At 3 months , teriparatide increased lumbar spine BMD significantly more than did alendronate ( P Lumbar spine-BMD increased by 12.2 % in the teriparatide group and 5.6 % in the alendronate group ( P alendronate ) . Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate , but BMD at the one third distal radius decreased , compared with alendronate ( P Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group ( P tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment . In conclusion , teriparatide , a bone formation agent , increased BMD at most sites and decreased nonvertebral fractures more than alendronate", "OBJECTIVE To re-examine the minimal effective dose of conjugated estrogen (CEE)-progestin hormone replacement on postmenopausal bone loss . DESIGN A 2-year , prospect i ve , open label , r and omized study . SETTING Department of Obstetrics and Gynecology of a university hospital . PARTICIPANTS Fifty-two postmenopausal or oophorectomized women . INTERVENTION One of the following regimens was continuously administered for 2 years : ( 1 ) CEE 0.625 mg/day , ( 2 ) CEE 0.625 mg + medroxyprogesterone ( MPA ) 2.5 mg/day , ( 3 ) CEE 0.31 mg + MPA 2.5 mg/day and ( 4 ) control . MEASUREMENTS Lumbar spine and femoral BMD by dual energy X-ray absorptiometry ( DXA ) , a monthly based incidence of bleeding , serum lipids , PTH , calcitonin . A1-p , and osteocalcin . RESULTS Of the 52 patients enrolled in this study , 49 patients completed the 1 year of therapy and 36 completed the 2- year study . The control group showed a significant decrease in lumbar BMD over the 2 years ( P % changes in lumbar BMD at 2 years of CEE alone , CEE 0.625 + MPA and CEE 0.31 + MPA were 8.52 % ( 95 % confidence intervals ; 4.61 approximately 12.4 % ) , 7.4 % ( 0.60 approximately 14.2 % ) and 3.20 % ( 0.61 approximately 5.84 % ) , respectively , and were significantly higher than pretreatment values . The incidence of bleeding was significantly lower in women taking CEE 0.31 mg + MPA . HDL cholesterol increased in women taking CEE 0.625 mg alone or with MPA . No significant changes in lipid profiles were seen in the control or in the group of women taking CEE 0.31 mg + MPA . CONCLUSIONS Continuous hormone replacement therapy ( HRT ) using 0.31 mg of CEE and 2.5 mg of MPA is effective in increasing lumbar BMD in postmenopausal or oophorectomized women and can be an appropriate option for women with a normal lipid profile or those women wishing to eliminate unscheduled bleeding", "Purpose of review Provide evidence -based recent data on oral micronized progesterone ( OMP ) and progestins in menopausal hormonal therapy ( MHT ) . Recent findings Medroxyprogesterone acetate ( MPA ) increases breast cancer acting through the glucocorticoid receptor ; progestins in MHT increase thrombosis more than oral estrogens ; MPA , but not OMP or other progestins , increase monocyte cell endothelium adhesion ; MPA and estradiol (E2)/MPA have negative brain effects , whereas E2/progesterone ( P4 ) has neuroregenerative brain effects . The ‘ window of opportunity ’ cardiovascular disease hypothesis is not supported by a r and omized controlled trial showing that transdermal estradiol with sequential OMP in early menopause does not prevent increased carotid intimal media thickness ; P4 in the cardiac electrical system opposes E2 effects and prevents sudden death/long QT syndrome ; transdermal estradiol/OMP does not increase venous thromboembolism in observational data . P4 decreases breast cell proliferation and improves prognosis through P4 receptor alteration of estrogen receptor & agr ; genetic effects ; OMP with conjugated equine estrogen (CEE)/estrogen (E)/E2 does not increase breast cancer in two prospect i ve cohorts , one population -based . Endometrial cancer is increased in MHT of CEE/E/E2+cyclic OMP at 200 mg/day . Summary New data show CEE/E/E2+MPA/P mechanisms for negative breast cancer , venous thromboembolism , cardiovascular system , and brain effects . OMP/P4 counterbalances CEE/E/E2-related negative effects on breast cancer and long QT syndrome . OMP effectively treats vasomotor symptoms and sleep disturbances , and could safely be used alone for symptomatic menopause", "OBJECTIVE Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances . The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern , using treatment with cyclic medroxyprogesterone , with or without calcium supplementation , in physically active women with disturbed menstruation . DESIGN This study was a 1-year r and omized , double-blind , placebo-controlled trial . Women who were stratified by menstrual cycle disturbance were r and omized into four groups . The outcome variable was the change in spinal bone density measured by dual energy techniques . SETTING A large metropolitan area . PARTICIPANTS Sixty-one healthy , normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea , oligomenorrhea , anovulation , or short luteal phase cycles completed the study . INTERVENTION Therapies were cyclic medroxyprogesterone ( 10 mg/day for 10 days per month ) and calcium carbonate ( 1,000 mg/day of calcium ) in four groups : ( A ) ( n = 16 ) cyclic medroxyprogesterone plus calcium carbonate ; ( B ) ( n = 16 ) cyclic medroxyprogesterone with calcium placebo ; ( C ) ( n = 15 ) placebo medroxyprogesterone with active calcium ; or ( D ) ( n = 14 ) both medroxyprogesterone and calcium placebos . RESULTS The initial bone density ( mean = 1.12 g/cm2 ) did not differ by group ( P = 0.85 ) . The 1-year bone density change was strongly related to treatment with medroxyprogesterone ( P = 0.0001 ) and weakly to calcium ( P = 0.072 ) treatment . Bone density increased significantly ( + 1.7 % + /- 0.5 % , + /- SEM , P = 0.004 ) in the medroxyprogesterone-treated groups ( A and B ) , did not change in the calcium-treated group ( C ) ( -0.7 % + /- 0.6 % , P = 0.28 ) , and decreased on both placebos ( D ) ( -2.0 % + /- 0.6 % , P = 0.005 ) . CONCLUSIONS Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances . POTENTIAL CLINICAL SIGNIFICANCE : Amenorrhea , oligomenorrhea , anovulation , and short luteal phase cycles are common in premenopausal women and associated with spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing . This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group , whereas those subjects in the placebo group lost bone . Calcium supplementation appeared to be helpful but did not reach statistical significance . The implication s of these findings for the prevention of osteoporosis warrant further investigation", "OBJECTIVE To assess the effects of hormone therapy on bone mineral density ( BMD ) in the spine and hip of postmenopausal women . DESIGN A 3-year , multicenter , r and omized , double-blinded , placebo-controlled clinical trial . PARTICIPANTS A total of 875 healthy women aged 45 to 64 years recruited at 7 clinical centers . INTERVENTIONS Treatments were ( 1 ) placebo ; ( 2 ) conjugated equine estrogens ( CEE ) , 0.625 mg/d ; ( 3 ) CEE , 0.625 mg/d plus medroxyprogesterone acetate ( MPA ) , 10 mg/d for 12 d/mo ; ( 4 ) CEE , 0.625 mg/d plus MPA , 2.5 mg/d daily ; or ( 5 ) CEE , 0.625 mg/d plus micronized progesterone ( MP ) , 200 mg/d for 12 d/mo . MAIN OUTCOME MEASURES Bone mineral density at baseline , 12 months , and 36 months . RESULTS Participants assigned to the placebo group lost an average of 1.8 % of spine BMD and 1.7 % of hip BMD by the 36-month visit , while those assigned to active regimens gained BMD at both sites , ranging from 3.5 % to 5.0 % mean total increases in spinal BMD and a mean total increase of 1.7 % of BMD in the hip . Changes in BMD for women assigned to active regimens were significantly greater than those assigned to placebo . Women assigned to CEE plus continuous MPA had significantly greater increases in spinal BMD ( increase of 5 % ) than those assigned to the other 3 active regimens ( average increase , 3.8 % ) . Findings were similar among those adhering to assigned therapy , although , among adherent participants , there were no significant differences in BMD changes among the 4 active treatment groups . Older women , women with low initial BMD , and those with no previous hormone use gained significantly more bone than younger women , women with higher initial BMD , and those who had used hormones previously . CONCLUSIONS Postmenopausal women assigned to placebo demonstrated decreased BMD at the spine and hip , whereas women assigned to estrogen therapy increased BMD during a 36-month period . These findings demonstrate that estrogen replacement therapy increases BMD at clinical ly important sites", "CONTEXT Lower-than-commonly-prescribed doses of conjugated equine estrogens ( CEEs ) with medroxyprogesterone acetate ( MPA ) improve vasomotor symptoms and vaginal atrophy , provide acceptable bleeding and lipid profiles , and afford endometrial protection . This lower-dose therapy 's protection against loss of bone mineral density ( BMD ) associated with menopause has not been thoroughly investigated . OBJECTIVE To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD , total body bone mineral content ( BMC ) , and biochemical markers of bone turnover in postmenopausal women . DESIGN AND SETTING Two-year r and omized , double-blind , placebo-controlled sub study of the Women 's Health , Osteoporosis , Progestin , Estrogen trial , conducted at 19 US centers between August 1995 and October 2000 . PARTICIPANTS Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period . INTERVENTIONS Patients were r and omly assigned to receive CEEs , 0.625 ; CEEs , 0.625 and MPA , 2.5 ; CEEs , 0.45 ; CEEs , 0.45 and MPA , 2.5 ; CEEs , 0.45 and MPA , 1.5 ; CEEs , 0.3 ; CEEs 0.3 and MPA , 1.5 ( all doses in mg/d ) ; or placebo for 2 years . All participants also received elemental calcium at 600 mg/d . MAIN OUTCOME MEASURES Changes from baseline in spine and total hip BMD , total body BMC , and biochemical markers of bone turnover ( serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen ) , assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach . RESULTS At 24 months , women assigned to all of the active treatment groups had significant gains from baseline ( P spine and hip BMD and total body BMC ( except total body BMC in the group receiving CEEs , 0.3 mg/d ) . These changes were significantly different from those in the placebo group , in which losses of bone mass in spine and total body were evident over the course of the study ( P loss in hip BMD from baseline in the placebo group was significant at 18 ( P = .02 ) but not at 24 months ( P = .06 ) . Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline ( P placebo group . For women treated with CEEs alone , the gains in spine BMD for the group taking CEEs , 0.625 mg/d , were significantly higher than those of the group taking CEEs , 0.3 mg/d ( P = .02 ) , but not the group treated with CEEs , 0.45 mg/d ( P = .48 ) . CONCLUSIONS Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women", "CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women", "Objective To determine the relationships among bone mineral density changes , bone marker changes , and plasma estrogens in postmenopausal women receiving estrogen replacement therapy . Design A total of 406 postmenopausal women received 1,000 mg calcium and continuous esterified estrogens ( 0.3 mg , 0.625 mg , or 1.25 mg ) or placebo daily for up to 24 months . Bone mineral density and bone marker measurements were determined at 6-month intervals ; plasma estrogens were measured in a subset after 12 , 18 , and 24 months . Results Esterified estrogens produced significant increases in bone mineral density ( lumbar spine , hip ) compared with baseline and placebo at 6 , 12 , 18 , and 24 months . Bone markers decreased from baseline with all esterified estrogen doses relative to placebo . Bone marker changes at 6 months correlated negatively with bone mineral density changes at 24 months ( correlation coefficient range = −0.122 to −0.439 ) . The strongest correlation was noted for spine bone mineral density changes and serum osteocalcin . Mean plasma estrogen levels increased with esterified estrogen dose , and bone mineral density changes correlated positively with plasma estrogen levels . Positive bone mineral density changes were noted in treatment groups with plasma estradiol levels at and above 25 pg/mL. Conclusions Esterified estrogens , at doses from 0.3 mg to 1.25 mg/day , unopposed by progestin , increase bone mineral density of the spine and hip in postmenopausal women . These bone mineral density changes correlated significantly with bone marker changes at 6 months and with plasma estrogens at 12 , 18 , or 24 months . Data variability minimizes the predictive value of the bone marker changes in monitoring individual therapy", "CONTEXT In the Women 's Health Initiative trial of estrogen-plus-progestin therapy , women assigned to active treatment had fewer fractures . OBJECTIVE To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial ( September 1993-July 2002 ) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years . INTERVENTION Women were r and omly assigned to receive conjugated equine estrogen , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial ( July 7 , 2002 ) ; bone mineral density ( BMD ) , measured in a subset of women ( n = 1024 ) at baseline and years 1 and 3 ; and a global index , developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk . RESULTS Seven hundred thirty-three women ( 8.6 % ) in the estrogen-plus-progestin group and 896 women ( 11.1 % ) in the placebo group experienced a fracture ( hazard ratio [ HR ] , 0.76 ; 95 % confidence interval [ CI ] , 0.69 - 0.83 ) . The effect did not differ in women stratified by age , body mass index , smoking status , history of falls , personal and family history of fracture , total calcium intake , past use of hormone therapy , BMD , or summary fracture risk score . Total hip BMD increased 3.7 % after 3 years of treatment with estrogen plus progestin compared with 0.14 % in the placebo group ( P HR for the global index was similar across tertiles of the fracture risk scale ( lowest fracture risk tertile , HR , 1.20 ; 95 % CI , 0.93 - 1.58 ; middle tertile , HR , 1.23 ; 95 % CI , 1.04 - 1.46 ; highest tertile , HR , 1.03 ; 95 % CI , 0.88 - 1.24 ) ( P for interaction = .54 ) . CONCLUSIONS This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women . The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined . When considering the effects of hormone therapy on other important disease outcomes in a global model , there was no net benefit , even in women considered to be at high risk of fracture" ]	41184ad2-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To determine the method ological quality of clinical trials that examined possible interactions of St John 's wort with conventional drugs , and to examine the results of these trials . DESIGN Systematic review . DATA SOURCES Electronic data bases from inception to April 2004 , reference lists from published reports , and experts in the field . STUDY SELECTION Eligible studies were prospect i ve clinical trials evaluating the pharmacokinetic effect of St John 's wort on the metabolism of conventional drugs . DATA EXTRACTION Two review ers selected studies for inclusion and independently extracted data . DATA SYNTHESIS 22 pharmacokinetic trials studied an average of 12 ( SD 5 ) participants ; 17 trials studied healthy volunteers and five studied patients . Most ( 17 ) studies used a " before and after " design ; four studies used control groups other than the active group . Three studies r and omised the sequence of administration or the participants to study arms or periods ; three studies blinded participants or investigators . In 15 trials , investigators independently assayed the herb . Of 19 trials with available plasma data , three found no important interaction ( change in area under the curve in systemic bioavailability of the conventional drug ; in seven studies the 95 % confidence interval excluded a decrease of systemic bioavailability of conventional drugs when taken concomitantly with St John 's wort	[ "AIMS Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John 's wort extract . The aim of the present study was to investigate the effects of St John 's wort extract on oral contraceptive therapy with respect to ovarian activity , breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel . METHODS Eighteen healthy females were treated with a low-dose oral contraceptive ( 0.02 mg ethinyloestradiol , 0.150 mg desogestrel ) alone ( control cycle ) or combined with 300 mg St John 's wort extract given twice daily ( cycle A ) or three times daily ( cycle B ) . Ovarian activity was assessed by measuring follicle maturation and serum oestradiol and progesterone concentrations . The number of breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel were assessed under steady-state conditions . RESULTS During concomitant administration of low-dose oral contraceptive and St John 's wort , there was no significant change in follicle maturation , serum oestradiol or progesterone concentrations when compared with oral contraceptive treatment alone . However , significantly more subjects reported intracyclic bleeding during cycles A ( 13/17 ( 77 % ) , P AUC(0,24 h ) and Cmax of ethinyloestradiol remained unchanged during all study cycles , whereas the AUC(0,24 h ) and Cmax of 3-ketodesogestrel decreased significantly from 31.2 ng ml-1 h to 17.7 ng x ml-1 h ( 43.9 % ; 95 % confidence interval ( CI ) -49.3 , -38.5 , P = 0.001 ) and from 3.6 ng x ml -1 to 3.0 ng x ml -1(17.8 % ; CI -29.9 , -5.7 , P = 0.005 ) , respectively , during cycle A and by 41.7 % ( CI -47.9 , -35.6 ; P = 0.001 ) and by 22.8 % ( CI -31.2 , -13.3 ; P ovulation during low-dose oral contraceptive and St John 's wort extract combination therapy , but intracyclic bleeding episodes increased . Bleeding irregularities may adversely effect compliance to oral contraceptives and together with St John 's wort-induced decreases in serum 3-ketodesogestrel concentrations , enhance the risk of unintended pregnancies", "Many drugs are cosubstrates of cytochrome P450 ( CYP ) 3A and MDR1 ; furthermore , their disposition is markedly affected by pretreatment with inducing agents , including St John 's wort . Such drug interactions reflect induction of both proteins through a common mechanism involving the steroid X receptor/pregnane X receptor . However , the relative contributions of enhanced metabolism and efflux transport to the overall induction process are unknown", "The popular herbal remedy St John 's wort is an inducer of cytochrome P450 ( CYP ) 3A enzymes and may reduce the efficacy of oral contraceptives . Therefore we evaluated the effect of St John 's wort on thedisposition and efficacy of Ortho‐Novum 1/35 ( Ortho‐McNeil Pharmaceutical , Inc , Raritan , NJ ) , a popular combination oral contraceptive pill containing ethinyl estradiol ( INN , ethinylestradiol ) and norethindrone ( INN , norethisterone ) ", "The objective of this study was to investigate the effect of St. John 's wort ( SJW , Hypericum perforatum ) on the pharmacokinetics of theophylline in healthy volunteers . Twelve healthy Japanese male volunteers participated in this r and omized , open-labeled , crossover study . The subjects took an SJW caplet ( 300 mg ) three times a day for 15 days . On day 14 , they received a single oral dose of 400 mg of theophylline . They took the same dose of theophylline without SJW treatment on another occasion . Plasma and urine sample s were obtained during a 48-hour period after theophylline administration . Theophylline concentrations in plasma and urine , as well as the major metabolites ( 13U , 1U , 3X ) in urine , were measured . SJW caused no significant changes in the pharmacokinetics of theophylline in plasma . SJW administration tended to increase the ratio of 1U/the total amount excreted in urine . However , no changes in the ratio of unchanged theophylline , 13U , and 3X were observed . It is unlikely that the effect of 15 days of treatment with SJW on CYPs is sufficient to cause a change in plasma theophylline concentrations", "UNLABELLED M : The aim of this study was to investigate the effect of St John 's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin . METHODS This was an open-label , three-way crossover r and omized study in 12 healthy male subjects , who received a single 25-mg dose of warfarin alone or after 14 days ' pretreatment with St John 's wort , or 7 days ' pretreatment with ginseng . Dosing with St John 's wort or ginseng was continued for 7 days after administration of the warfarin dose . Platelet aggregation , international normalized ratio ( INR ) of prothrombin time , warfarin enantiomer protein binding , warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured . Statistical comparisons were made using anova and 90 % confidence intervals are reported . RESULTS INR and platelet aggregation were not affected by treatment with St John 's wort or ginseng . The apparent clearances of S-warfarin after warfarin alone or with St John 's wort or ginseng were , respectively , 198 + /- 38 ml h(-1 ) , 270 + /- 44 ml h(-1 ) and 220 + /- 29 ml h(-1 ) . The respective apparent clearances of R-warfarin were 110 + /- 25 ml h(-1 ) , 142 + /- 29 ml h(-1 ) and 119 + /- 20 ml h(-1 ) [ corrected ] . The mean ratio and 90 % confidence interval ( CI ) of apparent clearance for S-warfarin was 1.29 ( 1.16 , 1.46 ) and for R-warfarin it was 1.23 ( 1.11 , 1.37 ) when St John 's wort was coadministered . The mean ratio and 90 % CI of AUC(0 - 168 ) of INR was 0.79 ( 0.70 , 0.95 ) when St John 's wort was coadministered . St John 's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers . CONCLUSIONS St John 's wort significantly induced the apparent clearance of both S-warfarin and R-warfarin , which in turn result ed in a significant reduction in the pharmacological effect of rac-warfarin . Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin", "St John 's Wort , a widely used herbal product , is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates . The effects of St John 's Wort on the pharmacokinetics of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors simvastatin ( an inactive lactone pro‐drug ) and pravastatin were determined in this study", "St John 's wort(Hypericum perforatum ) is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with substrates of several cytochrome P450 ( CYP ) isozymes . The effect of St John 's wort on CYP activity in vivo was examined with a probe drug cocktail", "St John 's wort is a popular over‐the‐counter dietary supplement and herbal remedy that has been implicated in drug interactions with several substrates of P‐glycoprotein . The effect of St John 's wort on P‐glycoprotein activity in vivo was examined with use of fexofenadine as selective probe drug", "Tacrolimus is an immunosuppressant approved for the prevention of rejection following transplantation and is a substrate for CYP3A and P-glycoprotein . A pharmacokinetic interaction between St. John 's wort ( antidepressant herbal product and inducer of CYP3A and P-glycoprotein ) and tacrolimus was evaluated in 10 healthy volunteers . The pharmacokinetics of tacrolimus were obtained from serial blood sample s collected following single oral doses ( 0.1 mg/kg ) prior to and during an 18-day concomitant St. John 's wort dosing phase ( 300 mg orally three times daily ) . Coadministration of St. John 's wort significantly decreased tacrolimus AUC ( 306.9 microg.h/L + /- 175.8 microg.h/L vs. 198.7 microg.h/L + /- 139.6 microg.h/L ; p=0.004 ) and increased apparent oral clearance ( 349.0 mL/h/kg + /- 126.0 mL/h/kg vs. 586.4 mL/h/kg + /- 274.9 mL/h/kg ; p=0.01 ) and apparent oral volume of distribution at steady state ( 11.5 L/kg + /- 4.3 L/kg vs. 17.6 L/kg + /- 9.6 L/kg ; p=0.04 ) . St. John 's wort appears to induce tacrolimus metabolism , most likely through induction of CYP3A and P-glycoprotein", " Extracts of St John 's wort ( Hypericum perforatum ) are widely used in the treatment of depression , often as an over‐the‐counter drug . In contrast to its frequent use , knowledge about the pharmacokinetics of ingredients and drug interactions of St John 's wort is poor . We studied the interaction between hypericum extract LI160 and digoxin", "OBJECTIVES Many cl aims are made that complementary medicine use is a substantial and growing part of health-care behaviour . Estimates of practitioner visits in the USA and Australia indicate high levels of use and expenditure . No reliable population -based estimates of practitioner use are available for the UK . METHODS In 1998 , a previously piloted postal question naire was sent to a geographically stratified , r and om sample of 5010 adults in Engl and . The question naire focuses on practitioner contacts , but also asked about the purchase of over-the-counter remedies . Additional information was requested on socio-demographic characteristics , perceived health , and recent NHS re source use . Information on use included reason for encounter , expenditure , insurance , and location of visit . MAIN OUTCOMES MEASURES Population estimates ( by age group and sex ) of lifetime use and use in the past 12 months for acupuncture , chiropractic , homoeopathy , hypnotherapy , medical herbalism , osteopathy . Estimates for two additional therapies ( reflexology and aromatherapy ) , and homoeopathic or herbal remedies purchased over-the-counter . Estimates of annual out-of-pocket expenditure on practitioner visits in 1998 . RESULTS A crude response rate of 60 % was achieved ( adjusted response rate 59 % ) . Responders were older and more likely to be female than non-responders . Usable responses ( n = 2669 ) were weighted using the age/sex profile of the sample frame . From these adjusted data we estimate that 10.6 % ( 95 % CI 9.4 to 11.7 ) of the adult population of Engl and had visited at least one therapist providing any one of the six more established therapies in the past 12 months ( 13.6 % for use of any of the eight named therapies , 95 % CI 12.3 to 14.9 ) . If all eight therapies , and self-care using remedies purchased over the counter are included , the estimated proportion rises to 28.3 % ( 95 % CI 26.6 to 30.0 ) for use in the past 12 months , and 46.6 % ( 95 % CI 44.6 to 48.5 ) for lifetime use . All types of use declined in older age groups , and were more commonly reported by women than men ( P expenditure . Annual out-of-pocket expenditure on any of the six more established therapies was estimated at pound 450 million ( 95 % CI 357 to 543 ) . CONCLUSION This survey has demonstrated substantial use of practitioner-provided complementary therapies in Engl and in 1998 . The findings suggest that CAM is making a measurable contribution to first-contact primary care . However , we have shown that 90 % of this provision is purchased privately . Further research into the cost-effectiveness of different CAM therapies for particular patient groups is now urgently needed to facilitate equal and appropriate access via the NHS" ]	41184b4a-06ff-11f0-808a-c43d1ab1c353
AIM To determine to what extent does calcium hydroxide intracanal medication eliminate bacteria from human root canals , compared with the same canals before medication , as measured by the number of positive cultures , in patients undergoing root canal treatment for apical periodontitis ( teeth with an infected root canal system ) . METHODOLOGY CENTRAL , MEDLINE and EMBASE data bases were search ed . Reference lists from identified articles were scanned . A forward search was undertaken on the authors of the identified articles . Papers that had cited these articles were also identified through the Science Citation Index to identify potentially relevant subsequent primary research . REVIEW METHODS The included studies were pre-/post-test clinical trials comparing the number of positive bacterial cultures from treated canals . Data in those studies were independently extracted . Risk differences of included studies were combined using the generic inverse variance and r and om effect method . RESULTS Eight studies were identified and included in the review , covering 257 cases . Sample size varied from 18 to 60 cases ; six studies demonstrated a statistically significant difference between pre- and post-medicated canals , whilst two did not . There was considerable heterogeneity among studies . Pooled risk difference was -21 % ; 95 % CI : -47 % to 6 % . The difference between pre- and post-medication was not statistically significant ( P = 0.12 ) . CONCLUSIONS Calcium hydroxide has limited effectiveness in eliminating bacteria from human root canal when assessed by culture techniques	[ "OBJECTIVE The dentin pH at different sites following placement of calcium hydroxide paste using 2 different methods was evaluated . STUDY DESIGN One hundred twenty Extracted teeth were instrumented and r and omly divided into 6 different groups . Then they were dressed with calcium hydroxide by 2 different methods using paper points or Lentulo spiral , according to their respective groups , and stored . After the experimental period of time , half of the sample s were cut transversally into slices and the other half split longitudinally and rinsed with distilled water . The dentin pH of cervical , middle , and apical thirds was measured from the root canal wall surface and 1 mm away from the root canal lumen in the inner dentin . The results were compared and statistically analyzed . RESULTS The highest pH values were obtained on the root canal walls when the calcium hydroxide was placed with Lentulo spiral filler ( P > .05 ) . There was a significant reduction in pH values in the inner dentin . When the cross sections of teeth were compared at 7 days , the Lentulo group was statistically different only in the apical third . CONCLUSIONS Placement of the calcium hydroxide paste with a Lentulo spiral with subsequent compaction with the blunt end of a sterile paper point obtained a higher pH value on the canal walls and in the inner dentin than paper points only", "The purpose of this study was to compare intracanal bacterial reduction on teeth instrumented with 0.04 tapered nickel-titanium ( NiTi ) rotary instrumentation to bacterial reduction when using a stainless-steel K-file step-back technique using sterile saline irrigation . Forty-eight patients with apical periodontitis were r and omly assigned treatment type . The canals were sample d before , during , and after instrumentation . The sample s were incubated anaerobically for 7 days at 37 degrees C , colony-forming unit numbers calculated , and a log transformation performed to normalize the counts . Teeth exhibiting apical periodontitis were uniformly infected , whereas vital control teeth were not . A similar and uniform reduction occurred with progressive filing , regardless of technique ( p colony-forming unit count after NiTi rotary or stainless-steel h and instrumentation ( p = 0.42 ) . Neither technique could predictably render canals free of bacteria . The results of this study indicate NiTi rotary and stainless-steel h and K-file step-back instrumentation techniques were not significantly different in their ability to reduce intracanal bacteria", "The objective was to evaluate the clinical efficacy of chemomechanical preparation of the root canals with sodium hypochlorite and interappointment medication with calcium hydroxide in the control of root canal infection and healing of periapical lesions . Fifty teeth diagnosed with chronic apical periodontitis were r and omly allocated to one of three treatments : Single visit ( SV group , n = 20 ) , calcium hydroxide for one week ( CH group n = 18 ) , or leaving the canal empty but sealed for one week ( EC group , n = 12 ) . Microbiological sample s were taken to monitor the infection during treatment . Periapical healing was controlled radiographically following the change in the periapical index at 52 wk and analyzed using one-way ANOVA . All cases showed microbiological growth in the beginning of the treatment . After mechanical preparation and irrigation with sodium hypochlorite in the first appointment , 20 to 33 % of the cases showed growth . At the second appointment 33 % of the cases in the CH group revealed bacteria , whereas the EC group showed remarkably more culture positive cases ( 67 % ) . Sodium hypochlorite was effective also at the second appointment and only two teeth remained culture positive . Only minor differences in periapical healing were observed between the treatment groups . However , bacterial growth at the second appointment had a significant negative impact on healing of the periapical lesion ( p clinical efficacy of sodium hypochlorite irrigation in the control of root canal infection . Calcium hydroxide dressing between the appointments did not show the expected effect in disinfection the root canal system and treatment outcome , indicating the need to develop more efficient inter-appointment dressings", "The antimicrobial efficacy of endodontic procedures performed in one-visit ( including a 10-min intraappointment dressing with 5 % iodine-potassium-iodide ) was compared with a two-visit procedure ( including an interappointment dressing with calcium-hydroxide paste ) . Teeth with apical periodontitis ( n = 96 ) were r and omly assigned to either group . Root canal sampling and culturing were performed before and immediately after instrumentation , and after medication . Initial sampling demonstrated the presence of microorganisms in 98 % of the teeth . Postinstrumentation sampling showed reduction of cultivable microbiota . Antibacterial dressing further reduced the number of teeth with surviving microbes . In the postmedication sample s , residual microorganisms were recovered in 29 % of the one-visit teeth and in 36 % of the two-visit treated teeth . No statistically significant differences between the groups were discerned . It was concluded that from a microbiological point of view , treatment of teeth with apical periodontitis performed in two appointments was not more effective than the investigated one-visit procedure", "The present investigation was design ed to study the effect of clindamycin on root canal infection when placed as an intracanal dressing . Twenty-five teeth with necrotic pulps and periapical radiolucencies were included . Following initial bacteriological sampling and routine instrumentation , clindamycin powder mixed to a paste with saline was applied for 14 days . The presence or absence of bacteria was determined in sample s taken immediately after removal of the dressing , and after a period of 7 days during which the canals were filled with sampling fluid . Bacteria were recovered from four and six teeth respectively . The results indicated that clindamycin offered no advantage over conventional root canal dressings , such as calcium hydroxide , and it is therefore not recommended for use in routine endodontic therapy", "AIM The aim of this study was to evaluate the fate of microorganisms in root canals of teeth with infected pulps and periapical bone lesions with and without the use of calcium hydroxide medication . METHODOLOGY Endodontic sample s were cultured and microorganisms were counted and identified in 43 teeth before ( sample 1 ) and after ( sample 2 ) treatment during the first visit and before ( sample 3 ) and after ( sample 4 ) treatment during the second visit . In the first visit teeth were instrumented and half of the teeth were filled with a thick slurry of calcium hydroxide in sterile saline . The other teeth were obturated with gutta-percha and AH-2 6 sealer . After 4 weeks the teeth with calcium-hydroxide were accessed again and after microbiological sampling they were obturated with gutta-percha and AH-26 sealer . RESULTS The mean total colony forming unit ( CFU ) counts of positive sample s dropped significantly as a result of canal preparation during the first visit from 1.0 x 10(6 ) to 1.8 x 10(3 ) ( between sample s 1 and 2 ) but increased to 9.3 x 10(3 ) in the period between the two visits ( sample 2 and 3 ) . There was no difference in mean total CFU counts of positive sample s between the end of the first ( sample 2 ) and the end of the second visit ( sample 4 ) . The most frequently isolated species were Prevotella intermedia , Capnocytophaga spp .. Actinomyces odontolyticus . Propionibacterium acnes and Peptostreptococcus micros . CONCLUSIONS Although a calcium hydroxide paste was placed in the prepared canals , the number of positive canals had increased in the period between visits . However , the number of microorganisms had only increased to 0.93 % of the original number of CFU ( sample 1 ) . It is concluded that a calcium hydroxide and sterile saline slurry limits but does not totally prevent regrowth of endodontic bacteria", "AIMS The aim of this study was to determine the occurrence and role of yeasts , enteric gram-negative rods and Enterococcus species in root-filled teeth with chronic apical periodontitis , and the antimicrobial effect of iodine potassium iodide ( IKI ) irrigation . METHODOLOGY Forty symptom-free root-filled teeth with chronic apical periodontitis were included in the study . The patients were divided into two groups . In group A the canals were filled with calcium hydroxide for 10 - 14 days after cleaning and shaping ; in group B the canals were irrigated with IKI for 5 min after cleaning and shaping followed by a permanent root filling . Microbiological sample s were taken from the canals before and after the chemomechanical preparation and after iodine irrigation ( group B ) . RESULTS Microbes were isolated from 33 of 40 teeth in the initial sampling . Yeasts were isolated from six teeth , three of them together with E. faecalis . Enteric rods ( Escherichia coli , Klebsiella pneumoniae and Proteus mirabilis ) were present in three teeth and E. faecalis was isolated from 21 of the 33 culture positive teeth , 11 in pure culture . Growth was detected in 10 teeth of the second sample s. Six of the 10 cases were E. faecalis , with five being a pure culture . All third sample s ( after IKI ) except one were negative . The number of microbial cells per sample did not correlate with lesion size . Two flare-ups were recorded , both in teeth with a mixed infection . CONCLUSION The high prevalence of enteric bacteria and yeasts in root-filled teeth with chronic apical periodontitis was established . IKI improved the antimicrobial effect of the treatment", "This study was conducted to determine the bacterial reduction using Profile GT files and a strict irrigation protocol utilizing 5.25 % NaOCl and EDTA . The additive antibacterial effect of Ca(OH)2 was also evaluated . In addition , the study compared the bacterial reduction with the GT protocol versus larger instrumentation . Thirty-one subjects with apical periodontitis were recruited . Bacterial sample s were taken upon access ( S1 ) , after instrumentation and a strict irrigation protocol ( S2 ) , and following > 1 wk of Ca(OH)2 ( SC ) . A log10 transformation of colony forming units was done since sample bacterial counts are not normally distributed . At S1 , 93.55 % of canals sample d bacteria . At S2 , 52.72 % of the cases sample d bacteria . At SC , 14 % of the cases cultured bacteria . The McNemar test showed a significant reduction ( p bacteria between S1 and S2 . This was also true between S2 and SC ( p GT protocol significantly reduced the number of bacteria in the canal but failed to render the canal bacteria free in more than half of the cases Ca(OH)2 application significantly further reduced bacteria . Lastly , large apical instrumentation removed more bacteria than small apical instrumentation", "This study was performed to evaluate radiographic healing of teeth with apical periodontitis , treated in one visit or in two visits ( a ) with or ( b ) without calcium hydroxide as an intracanal disinfecting medicament . The patients were assigned one of the three treatment groups by the throwing of a die . The Periapical Index ( PAI ) Scoring Method was used to compare differences in periapical status from the beginning of treatment to a 52-wk follow-up evaluation . Overall , the periapical status of the treated teeth improved significantly after 52 wk ( p PAI score of 1 or 2 was considered as representing a \" good \" periapical status while 3 , 4 , or 5 was a \" bad \" status . When base line PAI scores were controlled for , the calcium hydroxide group showed the most improvement in PAI score ( 3 , 4 , or 5 to 1 or 2 ) , followed by the one-step group ( 74 % vs. 64 % ) . The teeth that were left empty between visits had clearly inferior healing results . Power statistics were conducted to determine the numbers required for significant differences between the groups , and it was shown that large experimental groups on the order of hundreds of patients would be required to show significant differences" ]	41184c44-06ff-11f0-808a-c43d1ab1c353
Several decades of research have focused on the impact of exposure to postnatal depression on children , while anxiety has been largely overlooked . Estimates of the prevalence of postnatal maternal anxiety ( PMA ) range from 3 % to 43 % , suggesting PMA may be an important risk factor for adverse outcomes in children . This review summarizes what is known about the effects of PMA exposure on children and makes recommendations for future research . A systematic search of Ovid MEDLINE ® and PsychINFO ® through 2008 identified 18 studies that evaluated child outcomes associated with PMA exposure . Identified studies covered three domains : somatic , developmental , and psychological outcomes . The strongest evidence for an adverse effect of PMA exposure is in somatic and psychological outcomes ; the evidence for an effect of PMA on child development is inconclusive . Method ological differences among the studies make comparisons difficult and there are a number of common limitations that challenge the validity of these studies	[ "BACKGROUND Postnatal and antenatal depression are a focus of considerable clinical and research attention , but little is known about the patterns of anxiety across this period . METHODS Self-reported anxiety and depression were assessed at 18 and 32 weeks gestation and 8 weeks and 8 months postnatally in a prospect i ve longitudinal study of a community sample of women in Engl and ( n=8323 ) . RESULTS The majority of cases of postnatal depression were preceded by antenatal depression ; similarly , postnatal anxiety was preceded by antenatal anxiety . Despite the stability of anxiety and depression across this period , there was a mean decrease in both anxiety and depression . Finally , antenatal anxiety predicted postnatal depression at 8 weeks and 8 months , even after controlling for antenatal depression ( OR=3.22 , p antenatal anxiety occurs frequently , overlaps with depression and increases the likelihood of postnatal depression", "The Infant Temperament Question naire , originally published in 1970 , has been revised to improve its psychometric characteristics . The number of items was increased from 70 to 95 , rating options were increased from three to six , more items have high-low reversals , and they are r and omized as to content area . The new form was st and ardized on 203 4- to 8-month-old infants . Good test-retest reliability was maintained and internal consistency of the nine categories was raised to a higher level , thereby assuring a greater reliability of the instrument . These improvements should enhance the question naire 's use in clinical and research applications", "BACKGROUND Previous animal investigations link antenatal stress with a range of persistent behavioural abnormalities in the offspring . The current study examined if the effect was also found in humans through middle childhood . METHODS The current study is based on the Avon Longitudinal Study of Parents and Children ( ALSPAC ) , a prospect i ve , community-based study that has followed a cohort of women from pregnancy . Self-report measures of maternal anxiety and depression were assessed at repeated intervals in pregnancy and the postnatal period . Children 's behavioural/emotional problems were assessed by parent report at age 47 and 81 months . Information on obstetric and psychosocial factors was obtained at several points in pregnancy and the postnatal period . RESULTS Children whose mothers experienced high levels of anxiety in late pregnancy exhibited higher rates of behavioural/emotional problems at 81 months of age after controlling for obstetric risks , psychosocial disadvantage , and postnatal anxiety and depression ( for girls , OR = 1.91 , 95%CI = 1.26 - 2.89 ; for boys , OR = 2.16 , 95%CI = 1.41 - 3.30 ) . Furthermore , the effect at 81 months was comparable to what was previously obtained at 47 months , suggesting the kind of persistent effect proposed in the animal literature . CONCLUSIONS There is evidence that antenatal stress/anxiety has a programming effect on the fetus which lasts at least until middle childhood", "OBJECTIVE To assess whether parental psychological and physical factors and child factors measured in the first year of life were associated with recurrent abdominal pain ( RAP ) in children at age 6(3/4 ) years . METHOD A longitudinal cohort study ( the Avon Longitudinal Study of Parents and Children ) , followed 8,272 children from pregnancy to age 6(3/4 ) years . Parental reports of child and parent functioning were gathered . Associations between parental and child functioning assessed at 6 to 8 months postpartum , and RAP measured at age 6(3/4 ) years were investigated . RESULTS The prevalence of RAP in this sample was 11.8 % . Both maternal anxiety ( adjusted odds ratio = 1.53 ; 95 % confidence interval 1.24 - 1.89 ) and paternal anxiety ( adjusted odds ratio = 1.38 ; 95 % confidence interval 1.12 - 1.71 ) in the first year of a child 's life were associated with later childhood RAP . Parent reports of child temperament features such as irregular feeding and sleeping were also associated with later RAP . CONCLUSIONS This is the first evidence from a prospect i ve study that anxiety in both mothers and fathers and child temperament features pre date the occurrence of RAP in children . These findings highlight the potential importance of addressing parental anxiety in families in which children present with RAP , although some caution should be exercised in their interpretation because of possible reporting bias", " Primiparous women were divided into groups according to their post-partum trait anxiety scores . Professional or non-professional support for the first 12 months was offered to two subgroups of high trait anxiety subjects . At the 5-year follow-up the high-anxiety mothers ( n = 57 ) manifested more psychological and social pathology than moderate- and low-anxiety mothers ( n = 43 ) , and their children also showed signs of poorer adaptation . There was evidence of improved outcome for mothers in the professional intervention group , but not for their children . Child psychopathology was predicted best by maternal psychosocial variables , and to a lesser extent by child temperament variables . The relation of infant attachment and temperament measures to subsequent psychopathology is discussed", "Background : Infantile colic is a common problem of early infancy . There is limited data on the relation between postpartum maternal psychological problems and colic . Aim : : To investigate whether infantile colic is associated with postpartum mood disorders or insecure adult attachment style of the mother . Methods : Seventy eight mothers and newborns were enrolled in this prospect i ve , longitudinal study . Maternal depressive symptoms were screened with Edinburgh Postpartum Depression Score ( EPDS ) and maternal anxiety was assessed with State-Trait Anxiety Inventory ( STAI ) . The Adult Attachment Scale was used to determine the attachment style of the mother . Infantile colic was defined according to Wessel criteria . Results : Infantile colic was present in 17 infants ( 21.7 % ) ; 12.9 % of the mothers had an EPDS ⩾13 . The mean EPDS of the mothers whose infants had infantile colic ( 10.2±6.0 ) was significantly higher than that of the mothers of infants without colic ( 6.3±4.0 ) . Among infants with infantile colic , 62.5 % had mothers who had insecure attachment style , whereas only 31.1 % of mothers had insecure attachment when the infant did not have infantile colic . Conclusion : Postpartum maternal depressive symptoms and insecure attachment style are associated with infantile colic . Screening and early intervention of postpartum depression might promote the health of both the mother and infant", "BACKGROUND Although anxiety disorders are documented in the literature for new mothers ( but less so for fathers ) , rates of postpartum caseness tend to include only those with depression when diagnostic interviews or self-report measures vali date d on such interviews are used . This methodology therefore underestimates the true percentage of women and men who experience significant psychological difficulties postpartum . This has implication s for assessment , treatment and screening for postnatal mood disorders . METHOD Two studies were conducted on a total of 408 women and 356 men expecting their first child . They were recruited antenatally , and interviewed at 6 weeks postpartum using the Diagnostic Interview Schedule . DSM-IV criteria were applied to determine the presence since birth of depression ( major or minor ) , panic disorder , acute adjustment disorder with anxiety ( meeting the criteria for generalised anxiety disorder except for the duration criterion ) , and phobia . RESULTS The inclusion of diagnostic assessment for panic disorder and acute adjustment disorder with anxiety increased the rates of caseness by between 57 and 100 % for mothers , and 31 - 130 % for fathers , over the rates for major or minor depression . Inclusion of assessment for phobia further increased the rates of disorder in both sample s. Couple concordance rates were between 6.6 and 11.1 % , with no significant difference between rates for depressive or depressive and anxious caseness . For women , a previous history of an anxiety disorder appears to be a greater risk factor for a postnatal mood disorder ( i.e. depression or anxiety ) than a history of a depressive disorder . CONCLUSIONS These results clearly show the need to assess for both depression and anxiety in new and expectant parents , and we believe the term ' postnatal mood disorder ' ( PMD ) , rather than postnatal depression , more accurately reflects significant adjustment difficulties in new parents" ]	41184cbc-06ff-11f0-808a-c43d1ab1c353
Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibodies are powerful lipid-lowering drugs which have been shown to improve clinical endpoints in patients with hypercholesterolemia . However , it is not clear how effective PCSK9 monoclonal antibodies are for patients at high cardiovascular risk . Also , whether the effectiveness of PCSK9 monoclonal antibodies varies between different drug types , dosages , race , and indications for PCSK9 monoclonal antibodies remains unclear . Therefore , we used recently published studies to systematic ally evaluate the efficacy and safety of PCSK9 monoclonal antibodies by analyzing the lipid profiles , adverse events , and clinical endpoints in patients at high cardiovascular risk . R and omized controlled trials ( RCTs ) comparing PCSK9 monoclonal antibodies with placebos or active drugs in patients at high cardiovascular risk were retrieved from electronic data bases from their inception until November 2019 . Efficacy and safety outcomes included low-density lipoprotein cholesterol ( LDL-C ) and other lipid profiles , treatment-emergent adverse events ( TEAEs ) and adverse events of interests , and clinical endpoints . Subgroup analyses based on drug types , dosing , and race were conducted . Statistical analysis was performed using STATA 15.1 and RevMan 5.0 . Thirty-two RCTs were included in the systematic review , and 25 of them ( 57,090 individuals ) were included in the meta- analysis . PCSK9 monoclonal antibodies significantly improved LDL-C and other lipid profiles ( P of evolocumab every 2 weeks was likely to produce a relatively stronger effect than 150 mg of alirocumab every 2 weeks in terms of the absolute change ( weighted mean differences ( WMD ) − 0.36 ; 95 % confidence interval ( CI ) − 0.71 to − 0.01 ; P = 0.041 ) and percent change ( WMD − 19.53 ; 95 % CI − 32.02 to − 7.04 ; P = 0.002 ) in LDL-C levels . Overall , PCSK9 monoclonal antibodies were safe , except for the significantly increased risk of injection site reactions ( relative risks ( RR ) 1.54 ; 95 % CI 1.38–1.71 ; P risk of major cardiovascular events ( MACEs ) , especially in secondary preventive patients ( alirocumab group : RR 0.88 ; 95 % CI 0.82–0.95 ; P evolocumab group : RR 0.86 ; 95 % CI 0.80–0.92 ; P reduction in MACEs was observed in White but not in Asian subjects . No significant reduction of all-cause mortality was found ( RR 0.88 ; 95 % CI 0.72–1.07 ; P = 0.182 ) . Both alirocumab and evolocumab are well tolerated and can greatly improve lipid profiles for patients at high cardiovascular risk . Both PCSK9 monoclonal antibodies significantly reduce the risk of nonfatal MACEs in patients with previous cardiovascular events , but the effect on all-cause mortality remains uncertain	[ "BACKGROUND The ODYSSEY COMBO I study ( http:// clinical trials.gov/show/NCT01644175 ) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia . METHODS This multicenter , phase 3 , r and omized ( 2:1 alirocumab vs placebo ) , double-blind , 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia . Alirocumab ( 75 mg every 2 weeks [ Q2W ] ) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen . The alirocumab dose was increased to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 low-density lipoprotein cholesterol ( LDL-C ) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 ( intention-to-treat analysis ) . RESULTS At week 24 , estimated mean ( 95 % CI ) changes in LDL-C from baseline were -48.2 % ( -52.0 % to -44.4 % ) and -2.3 % ( -7.6 % to 3.1 % ) for alirocumab and placebo , respectively , an estimated mean ( 95 % CI ) difference of -45.9 % ( -52.5 % to -39.3 % ) ( P % alirocumab versus 9 % placebo patients at week 24 . At week 12 , 83.2 % of evaluable alirocumab-treated patients remained on 75-mg Q2W . Treatment-emergent adverse events were comparable between groups . CONCLUSIONS Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals , versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy . The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups", "Aims To compare the efficacy [ low-density lipoprotein cholesterol ( LDL-C ) lowering ] and safety of alirocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9 , compared with ezetimibe , as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia . Methods and results COMBO II is a double-blind , double-dummy , active-controlled , parallel-group , 104-week study of alirocumab vs. ezetimibe . Patients ( n = 720 ) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled ( August 2012–May 2013 ) . This pre-specified analysis was conducted after the last patient completed 52 weeks . Patients were r and omized to subcutaneous alirocumab 75 mg every 2 weeks ( plus oral placebo ) or oral ezetimibe 10 mg daily ( plus subcutaneous placebo ) on a background of statin therapy . At Week 24 , mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4 % for alirocumab vs. 20.7 ± 1.9 % for ezetimibe ( difference 29.8 ± 2.3 % ; P % of alirocumab and 45.6 % of ezetimibe patients achieved LDL-C LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe , and were maintained to Week 52 . Alirocumab was generally well tolerated , with no evidence of an excess of treatment-emergent adverse events . Conclusion In patients at high cardiovascular risk with inadequately controlled LDL-C , alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe , with a similar safety profile . Trial registration clinical trials.gov Identifier : NCT01644188", "Aim To evaluate the effect of alirocumab on frequency of st and ard apheresis treatments [ weekly or every 2 weeks ( Q2W ) ] in heterozygous familial hypercholesterolaemia ( HeFH ) . Methods and results ODYSSEY ESCAPE ( NCT02326220 ) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis . Patients were r and omly assigned ( 2:1 , respectively ) to receive alirocumab 150 mg ( n = 41 ) or placebo ( n = 21 ) Q2W subcutaneously for 18 weeks . From day 1 to week 6 , apheresis rate was fixed according to the patient ’s established schedule ; from weeks 7 to 18 , apheresis rate was adjusted based on the patient ’s low-density lipoprotein cholesterol ( LDL-C ) response in a blinded fashion . Apheresis was not performed when the LDL-C value was ≥30 % lower than the baseline ( pre-apheresis ) value . The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks ( weeks 7–18 ) , st and ardized to number of planned treatments . In the alirocumab group the least square ( LS ) mean ± SE ( 95 % confidence interval [ CI ] ) per cent change in pre-apheresis LDL-C from baseline at week 6 was −53.7 ± 2.3 ( −58.2 to − 49.2 ) compared with 1.6 ± 3.1 ( –4.7 to 7.9 ) in the placebo group . The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab ( Hodges – Lehmann median estimate of treatment difference : 0.75 ; 95 % CI 0.67–0.83 ; P , alirocumab-treated patients had a 0.75 ( 75 % ) additional reduction in the st and ardized rate of apheresis treatments vs. placebo-treated patients . During this period , 63.4 % of patients on alirocumab avoided all and 92.7 % avoided at least half of the apheresis treatments . Adverse event rates were similar ( 75.6 % of patients on alirocumab vs. 76.2 % on placebo ) . Conclusions Lipoprotein apheresis was discontinued in 63.4 % of patients on alirocumab who were previously undergoing regular apheresis , and the rate was at least halved in 92.7 % of patients . Alirocumab was generally safe and well tolerated", "Purpose Even with statins and other lipid-lowering therapy ( LLT ) , many patients with heterozygous familial hypercholesterolemia ( heFH ) continue to have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . ODYSSEY HIGH FH ( NCT01617655 ) assessed the efficacy and safety of alirocumab , a proprotein convertase subtilisin/kexin type 9 monoclonal antibody , versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT . Methods Patients were r and omized to subcutaneous alirocumab 150 mg or placebo every 2 weeks ( Q2W ) for 78 weeks . The primary endpoint was percent change in LDL-C from baseline to week 24 . Results Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab ( n = 71 ) and 201.0 mg/dl in the placebo groups ( n = 35 ) . Significant mean ( st and ard error [ SE ] ) reductions in LDL-C from baseline to week 24 were observed with alirocumab ( −45.7 [ 3.5 ] % ) versus placebo ( −6.6 [ 4.9 ] % ) , a difference of −39.1 ( 6.0 ) % ( P were reduced from baseline by 90.8 ( 6.7 ) mg/dl with alirocumab at week 24 , with reductions maintained to week 78 . Treatment-emergent adverse events were generally comparable between groups . Injection-site reactions were more frequent in the alirocumab group ( 8.3 % ) versus placebo ( 5.7 % ) ; most were mild in severity and did not result in study medication discontinuation . Conclusions In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT , alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals . Alirocumab was generally well tolerated", "BACKGROUND YUKAWA is a 12-week , r and omized , double-blind , placebo-controlled , phase 2 study evaluating the efficacy and safety of evolocumab ( AMG 145 ) in statin-treated Japanese patients at high cardiovascular risk . METHODS AND RESULTS 310 eligible patients receiving stable statin ( ±ezetimibe ) therapy were r and omized to 1 of 6 treatments : placebo every 2 weeks ( Q2W ) or monthly ( QM ) , evolocumab 70 mg or 140 mg Q2W , or evolocumab 280 mg or 420 mg QM . The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol ( LDL-C ) measured by preparative ultracentrifugation ( UC ) . Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C Mean ( SD ) age was 62 ( 10 ) years ; 37 % were female ; and the mean ( SD ) baseline LDL-C was 3.7 ( 0.5 ) mmol/L ( by UC ) . Mean ( SE ) changes vs. placebo in LDL-C were greatest in the high-dose groups : -68.6 ( 3.0 ) % and -63.9 ( 3.2 ) % with 140 mg Q2W and 420 mg QM dosing , respectively . Up to 96 % of evolocumab-treated patients achieved LDL-C mmol/L. Adverse events ( AEs ) were more frequent in evolocumab ( 51 % ) vs. placebo ( 38 % ) patients ; 4 patients taking evolocumab discontinued treatment because of an AE . There were no significant differences in AE rates based on dose or dose frequency . CONCLUSIONS In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy , evolocumab significantly reduced LDL-C and was well tolerated during this 12-week study", "Aims To assess long-term ( 78 weeks ) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia ( HeFH ) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy ( LLT ) . Methods and results In two r and omized , double-blind studies ( ODYSSEY FH I , n = 486 ; FH II , n = 249 ) , patients were r and omized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks ( Q2W ) . Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L ( 70 mg/dL ) . Primary endpoint ( both studies ) was percentage change in calculated LDL-C from baseline to Week 24 . Mean LDL-C levels decreased from 3.7 mmol/L ( 144.7 mg/dL ) at baseline to 1.8 mmol/L ( 71.3 mg/dL ; −57.9 % vs. placebo ) at Week 24 in patients r and omized to alirocumab in FH I and from 3.5 mmol/L ( 134.6 mg/dL ) to 1.8 mmol/L ( 67.7 mg/dL ; −51.4 % vs. placebo ) in FH II ( P 78 . LDL-C respectively . Adverse events result ed in discontinuation in 3.4 % of alirocumab-treated patients in FH I ( vs. 6.1 % placebo ) and 3.6 % ( vs. 1.2 % ) in FH II . Rate of injection site reactions in alirocumab-treated patients was 12.4 % in FH I and 11.4 % in FH II ( vs. 11.0 and 7.4 % with placebo ) . Conclusion In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT , alirocumab treatment result ed in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated . Clinical trial registration Cinicaltrials.gov ( identifiers : NCT01623115 ; NCT01709500 )", "CONTEXT Despite current st and ard of care , many patients at high risk of cardiovascular disease ( CVD ) still have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 . OBJECTIVE The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies . DESIGN , PATIENTS , AND INTERVENTIONS Patients ( n = 355 ) with very high CVD risk and LDL-C levels of 70 mg/dL or greater or high CVD risk and LDL-C of 100 mg/dL or greater on baseline atorvastatin 20 or 40 mg were r and omized to one of the following : 1 ) add-on alirocumab 75 mg every 2 weeks ( Q2W ) sc ; 2 ) add-on ezetimibe 10 mg/d ; 3 ) double atorvastatin dose ; or 4 ) for atorvastatin 40 mg regimen only , switch to rosuvastatin 40 mg . For patients not achieving protocol -defined LDL-C goals , the alirocumab dose was increased ( blinded ) at week 12 to 150 mg Q2W . MAIN OUTCOME MEASURE The primary end point was percentage change in calculated LDL-C from baseline to 24 weeks ( intent to treat ) . RESULTS Among atorvastatin 20 and 40 mg regimens , respectively , add-on alirocumab reduced LDL-C levels by 44.1 % and 54.0 % ( P ezetimibe , 20.5 % and 22.6 % ; doubling of atorvastatin dose , 5.0 % and 4.8 % ; and switching atorvastatin 40 mg to rosuvastatin 40 mg , 21.4 % . Most alirocumab-treated patients ( 87.2 % and 84.6 % ) achieved their LDL-C goals . Most alirocumab-treated patients ( 86 % ) maintained their 75-mg Q2W regimen . Treatment-emergent adverse events occurred in 65.4 % of alirocumab patients vs 64.4 % ezetimibe and 63.8 % double atorvastatin/switch to rosuvastatin ( data were pooled ) . CONCLUSIONS Adding alirocumab to atorvastatin provided significantly greater LDL-C reductions vs adding ezetimibe , doubling atorvastatin dose , or switching to rosuvastatin and enabled greater LDL-C goal achievement", "BACKGROUND Inhibition of proprotein convertase subtilisin/kexin type 9 serine protease ( PCSK9 ) result ed in large reductions of low-density lipoprotein cholesterol ( LDL-C ) in phase 1 trials . We assessed the efficacy and safety of various doses and dosing intervals of REGN727 , a monoclonal antibody to PCSK9 , added to statins , to further lower LDL-C in patients with heterozygous familial hypercholesterolaemia . METHODS This multicentre , r and omised , placebo-controlled phase 2 trial was done at 16 lipid clinics in the USA and Canada . Between Jan 18 , 2011 , and Nov 7 , 2011 , we enrolled adults with heterozygous familial hypercholesterolaemia and LDL-C concentrations of 2·6 mmol/L or higher on stable diet and statin dose , with or without ezetimibe . Patients were r and omly assigned to receive REGN727 150 mg , 200 mg , or 300 mg every 4 weeks , or 150 mg every 2 weeks , or placebo every 2 weeks ( ratio 1:1:1:1:1 ) . R and omisation was stratified by concomitant use of ezetimibe at baseline . Investigators , study staff , and patients were masked to treatment group . Blinding was maintained by administration of placebo alternating with REGN727 for the groups of 4 week dosing . The primary endpoint was mean percent reduction in LDL-C from baseline at week 12 and was analysed in the modified intention-to-treat population with an analysis of covariance ( ANCOVA ) model with treatment group . This trial is registered in Clinical Trials.gov , number NCT 01266876 . FINDINGS 77 patients were r and omly assigned to study groups ( 15 - 16 patients per group ) and all were analysed . Least-squares ( LS ) mean LDL-C reduction from baseline to week 12 was 28·9 % ( SE 5·08 ) for 150 mg every 4 weeks ( p=0·0113 ) , 31·54 % ( 4·91 ) for 200 mg every 4 weeks ( p=0·0035 ) , 42·53 % ( 5·09 ) for 300 mg every 4 weeks ( p ) with placebo . One serious adverse event was reported with placebo and none with REGN727 . No increases of more than three times the upper limit of normal were reported for hepatic transaminases or creatinine kinase . The most common adverse event was injection-site reaction with one patient in the group of 300 mg REGN727 terminating treatment . INTERPRETATION REGN727 was well tolerated and achieved substantial further LDL-C reduction in patients with heterozygous familial hypercholesterolaemia and elevated LDL-C treated with high-dose statins , with or without ezetimibe . REGN727 has the potential to provide optimum control of LDL-C in patients with this disorder . FUNDING Sanofi US and Regeneron Pharmaceuticals Incorporated", "BACKGROUND Alirocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , has been shown to reduce low-density lipoprotein ( LDL ) cholesterol levels in patients who are receiving statin therapy . Larger and longer-term studies are needed to establish safety and efficacy . METHODS We conducted a r and omized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter ( 1.8 mmol per liter ) or more and were receiving treatment with statins at the maximum tolerated dose ( the highest dose associated with an acceptable side-effect profile ) , with or without other lipid-lowering therapy . Patients were r and omly assigned in a 2:1 ratio to receive alirocumab ( 150 mg ) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks . The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24 . RESULTS At week 24 , the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points ( P alirocumab group , as compared with the placebo group , had higher rates of injection-site reactions ( 5.9 % vs. 4.2 % ) , myalgia ( 5.4 % vs. 2.9 % ) , neurocognitive events ( 1.2 % vs. 0.5 % ) , and ophthalmologic events ( 2.9 % vs. 1.9 % ) . In a post hoc analysis , the rate of major adverse cardiovascular events ( death from coronary heart disease , nonfatal myocardial infa rct ion , fatal or nonfatal ischemic stroke , or unstable angina requiring hospitalization ) was lower with alirocumab than with placebo ( 1.7 % vs. 3.3 % ; hazard ratio , 0.52 ; 95 % confidence interval , 0.31 to 0.90 ; nominal P=0.02 ) . CONCLUSIONS Over a period of 78 weeks , alirocumab , when added to statin therapy at the maximum tolerated dose , significantly reduced LDL cholesterol levels . In a post hoc analysis , there was evidence of a reduction in the rate of cardiovascular events with alirocumab . ( Funded by Sanofi and Regeneron Pharmaceuticals ; ODYSSEY LONG TERM Clinical Trials.gov number , NCT01507831 . )", "BACKGROUND Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol ( LDL-C ) concentrations . Current options for such patients include using a lower but tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies . METHODS ODYSSEY ALTERNATIVE ( NCT01709513 ) compared alirocumab with ezetimibe in patients at moderate to high cardiovascular risk with statin intolerance ( unable to tolerate ≥2 statins , including one at the lowest approved starting dose ) due to muscle symptoms . A placebo run-in and statin rechallenge arm were included in an attempt to confirm intolerance . Patients ( n = 361 ) received single-blind subcutaneous ( SC ) and oral placebo for 4 weeks during placebo run-in . Patients reporting muscle-related symptoms during the run-in were to be withdrawn . Continuing patients were r and omized ( 2:2:1 ) to double-blind alirocumab 75 mg SC every 2 weeks ( Q2W ; plus oral placebo ) , ezetimibe 10 mg/d ( plus SC placebo Q2W ) , or atorvastatin 20 mg/d ( rechallenge ; plus SC placebo Q2W ) for 24 weeks . Alirocumab dose was increased to 150 mg Q2W at week 12 depending on week 8 LDL-C values . Primary end point was percent change in LDL-C from baseline to week 24 ( intent-to-treat ) for alirocumab vs ezetimibe . RESULTS Baseline mean ( st and ard deviation ) LDL-C was 191.3 ( 69.3 ) mg/dL ( 5.0 [ 1.8 ] mmol/L ) . Alirocumab reduced mean ( st and ard error ) LDL-C by 45.0 % ( 2.2 % ) vs 14.6 % ( 2.2 % ) with ezetimibe ( mean difference 30.4 % [ 3.1 % ] , P .0001 ) . Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin ( hazard ratio 0.61 , 95 % confidence interval 0.38 - 0.99 , P = .042 ) . CONCLUSIONS Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients , with fewer skeletal-muscle adverse events vs atorvastatin ", "BACKGROUND Familial hypercholesterolemia ( FH ) is a dominant genetic disorder associated with elevated low-density lipoprotein cholesterol ( LDL-C ) and premature atherosclerotic events . Although therapeutic monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) are indicated for LDL-C reduction among adult patients with FH , placebo-controlled outcome data among FH patients are scant . OBJECTIVE Directly compare the efficacy of PCSK9 inhibition as compared to placebo on hard cardiovascular outcomes in FH patients enrolled in the Studies of PCSK9 Inhibition and the Reduction of vascular Events ( SPIRE ) program . METHODS We estimated the efficacy of PCSK9 inhibition with bococizumab on future cardiovascular event rates among 1578 FH patients and 15,959 patients without FH who were selected for comparable lipid levels ( on-statin levels of LDL-C > 100 mg/dL or non-high-density lipoprotein cholesterol > 130 mg/dL ) . All patients were r and omized by computer generated codes to bococizumab 150 mg subcutaneously every 2 weeks or to matching placebo in the SPIRE clinical trials program and were followed over a median period of 11.2 months for major adverse cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death ) . Analysis is by intention to treat . The SPIRE trials are closed and registered at Clinical Trials.gov : NCT01968954 , NCT01968967 , NCT02100514 , NCT01968980 , NCT01975376 , and NCT01975389 . RESULTS Compared to non-FH patients , FH patients enrolled in the SPIRE trials were on average younger ( 58 vs 63 years ) , more likely to be women ( 42 vs 35 % ) , more likely to be primary prevention patients ( 42 vs 23 % ) , had higher mean baseline LDL-C levels ( 151 vs 127 mg/dL ) , and lower rates of diabetes ( 25 vs 52 % ) and hypertension ( 59 vs 82 % ) . FH and non-FH patients both had 55 % reductions in LDL-C with bococizumab . Among FH patients , major adverse cardiovascular events occurred among 18 of 781 allocated to bococizumab and 22 of 797 allocated to placebo ( hazard ratio 0.83 ; 95 % confidence interval 0.44 - 1.54 , P = .55 ) . This best estimate of effect was similar in magnitude to that observed in the much larger group of patients without FH ( hazard ratio 0.79 , 95 % confidence interval 0.64 - 0.97 , P = .023 ) with no statistically significant evidence of heterogeneity between groups ( P = .87 ) . Incidence rate ratios comparing bococizumab to placebo for adverse events were similar among those with and without FH . The proportion of patients developing antidrug antibodies was higher among those with FH compared to those without FH ( 43 % vs 36 % , P statin-treated FH patients had a similar magnitude of risk reduction for hard cardiovascular events with the PCSK9 inhibitor bococizumab as did patients without FH , with no evidence of statistical heterogeneity between groups", "BACKGROUND The ODYSSEY Japan study was design ed to demonstrate the reduction in low-density lipoprotein cholesterol ( LDL-C ) by alirocumab as add-on to existing lipid-lowering therapy in Japanese patients with heterozygous familial hypercholesterolemia ( heFH ) or non-FH at high cardiovascular risk who require additional pharmacological management to achieve their LDL-C treatment goal ( METHODS AND RESULTS This r and omized , double-blind , parallel-group , 52-week study was conducted in Japan . Patients ( n=216 ) with heFH , non-FH at high cardiovascular risk with coronary disease , or classified as category III were enrolled . The prespecified safety analysis was done after the last patient completed 52 weeks . Patients were r and omized ( 2:1 , alirocumab : placebo ) with stratification for heFH to s.c . alirocumab ( 75 mg every 2 weeks [ Q2 W ] with increase to 150 mg if week 8 LDL-C ≥2.6/3.1 mmol/L ) or placebo for 52 weeks plus stable statin therapy . At week 24 , mean±SE change in LDL-C from baseline was -62.5±1.3 % in the alirocumab group and 1.6±1.8 % in the placebo group ( difference , -64.1±2.2 % ; P ( alirocumab , -62.5±1.4 % ; placebo , -3.6±1.9 % ) . No patterns were evident between treatment groups for adverse events at 52 weeks . CONCLUSIONS In high-risk Japanese patients with hypercholesterolemia on stable statin therapy , alirocumab markedly reduced LDL-C vs. placebo and was well tolerated over 52 weeks . ( Circ J 2016 ; 80 : 1980 - 1987 )", "Aims To investigate the efficacy and safety of alirocumab in participants with type 2 ( T2D ) or type 1 diabetes ( T1D ) treated with insulin who have elevated LDL cholesterol levels despite maximally tolerated statin therapy . Methods Participants at high cardiovascular risk with T2D ( n = 441 ) or T1D ( n = 76 ) and LDL cholesterol levels ≥1.8 mmol/L ( ≥70 mg/dL ) were r and omized 2:1 to alirocumab : placebo administered subcutaneously every 2 weeks , for 24 weeks ' double‐blind treatment . Alirocumab‐treated participants received 75 mg every 2 weeks , with blinded dose increase to 150 mg every 2 weeks at week 12 if week 8 LDL cholesterol levels were ≥1.8 mmol/L. Primary endpoints were percentage change in calculated LDL cholesterol from baseline to week 24 , and safety assessment s. Results Alirocumab reduced LDL cholesterol from baseline to week 24 by a mean ± st and ard error of 49.0 % ± 2.7 % and 47.8 % ± 6.5 % vs placebo ( both P in non‐HDL cholesterol ( P ) , apolipoprotein B ( P and lipoprotein ( a ) ( P ≤ .0039 ) . At week 24 , 76.4 % and 70.2 % of the alirocumab group achieved LDL cholesterol respectively . Glycated haemoglobin and fasting plasma glucose levels remained stable for the study duration . Treatment‐emergent adverse events were observed in 64.5 % of alirocumab‐ vs 64.1 % of placebo‐treated individuals ( overall population ) . Conclusions Alirocumab produced significant LDL cholesterol reductions in participants with insulin‐treated diabetes regardless of diabetes type , and was generally well tolerated . Concomitant administration of alirocumab and insulin did not raise any safety concerns ( NCT02585778 )", "OBJECTIVE To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies ( NCT01730053 ) . METHODS Patients receiving baseline rosuvastatin regimens ( 10 or 20 mg ) were r and omized to : add-on alirocumab 75 mg every-2-weeks ( Q2W ) ( 1-mL subcutaneous injection via pre-filled pen ) ; add-on ezetimibe 10 mg/day ; or double-dose rosuvastatin . Patients had cardiovascular disease ( CVD ) and low-density lipoprotein cholesterol ( LDL-C ) ≥70 mg/dL ( 1.8 mmol/L ) or CVD risk factors and LDL-C ≥100 mg/dL ( 2.6 mmol/L ) . In the alirocumab group , dose was blindly increased at Week 12 to 150 mg Q2W ( also 1-mL volume ) in patients not achieving their LDL-C target . Primary endpoint was percent change in calculated LDL-C from baseline to 24 weeks ( intent-to-treat ) . RESULTS 305 patients were r and omized . In the baseline rosuvastatin 10 mg group , significantly greater LDL-C reductions were observed with add-on alirocumab ( -50.6 % ) versus ezetimibe ( -14.4 % ; p baseline rosuvastatin 20 mg group , LDL-C reduction with add-on alirocumab was -36.3 % compared with -11.0 % with ezetimibe and -15.9 % with double-dose rosuvastatin ( p = 0.0136 and 0.0453 , respectively ; pre-specified threshold for significance p % alirocumab patients were maintained on 75 mg Q2W . Of alirocumab-treated patients , 84.9 % and 66.7 % in the baseline rosuvastatin 10 and 20 mg groups , respectively , achieved risk-based LDL-C targets . Treatment-emergent adverse events occurred in 56.3 % of alirocumab patients versus 53.5 % ezetimibe and 67.3 % double-dose rosuvastatin ( pooled data ) . CONCLUSIONS The addition of alirocumab to rosuvastatin provided incremental LDL-C lowering versus adding ezetimibe or doubling the rosuvastatin dose", "Evolocumab ( AMG 145 ) , a fully human monoclonal antibody against PCSK9 , significantly reduced low-density lipoprotein cholesterol ( LDL-C ) levels in phase 2 and 3 studies . This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk . Patients were r and omized to atorvastatin 5 or 20 mg/day for 4 weeks . Subsequently , patients underwent second r and omization to evolocumab 140 mg biweekly ( Q2W ) or 420 mg monthly ( QM ) or placebo Q2W or QM . Co primary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12 . Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C 70 mg/dl . Adverse events and laboratory values were recorded . Four hundred four patients were r and omized to study drug . At baseline , the mean ( SD ) age was 61 ( 10 ) years ( placebo ) and 62 ( 11 ) years ( evolocumab ) ; 39 % and 40 % were women ; 14 % and 12 % had cerebrovascular or peripheral arterial disease ; and 51 % and 47 % had diabetes . At entry , mean ( SD ) calculated LDL-C was 128 ( 23 ) mg/dL ; after stabilization on atorvastatin 5 and 20 mg/day , baseline LDL-C levels were 118 ( 35 ) and 94 ( 24 ) mg/dL , respectively . Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67 % to 76 % . No imbalances were observed in adverse events between treatment groups . Efficacy and safety for Q2W or QM evolocumab dosing were similar . In conclusion , in high-risk Japanese patients receiving stable statin therapy , evolocumab markedly reduced LDL-C and was well tolerated", "BACKGROUND Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol , increased plasma LDL cholesterol concentrations , and premature cardiovascular disease . Despite intensive statin therapy , with or without ezetimibe , many patients are unable to achieve recommended target levels of LDL cholesterol . We investigated the effect of PCSK9 inhibition with evolocumab ( AMG 145 ) on LDL cholesterol in patients with this disorder . METHODS This multicentre , r and omised , double-blind , placebo-controlled trial was undertaken at 39 sites ( most of which were specialised lipid clinics , mainly attached to academic institutions ) in Australia , Asia , Europe , New Zeal and , North America , and South Africa between Feb 7 and Dec 19 , 2013 . 331 eligible patients ( 18 - 80 years of age ) , who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks , with a fasting LDL cholesterol concentration of 2·6 mmol/L or higher , were r and omly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks , evolocumab 420 mg monthly , or subcutaneous placebo every 2 weeks or monthly for 12 weeks . R and omisation was computer generated by the study sponsor , implemented by a computerised voice interactive system , and stratified by LDL cholesterol concentration at screening ( higher or lower than 4·1 mmol/L ) and by baseline ezetimibe use ( yes/no ) . Patients , study personnel , investigators , and Amgen study staff were masked to treatment assignments within dosing frequency groups . The co primary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12 , analysed by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT01763918 . FINDINGS Of 415 screened patients , 331 were eligible and were r and omly assigned to the four treatment groups : evolocumab 140 mg every 2 weeks ( n=111 ) , evolocumab 420 mg monthly ( n=110 ) , placebo every 2 weeks ( n=55 ) , or placebo monthly ( n=55 ) . 329 patients received at least one dose of study drug . Compared with placebo , evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 ( every-2-weeks dose : 59·2 % reduction [ 95 % CI 53·4 - 65·1 ] , monthly dose : 61·3 % reduction [ 53·6 - 69·0 ] ; both p ] ; both p ) . Evolocumab was well tolerated , with rates of adverse events similar to placebo . The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis ( in 19 patients [ 9 % ] vs five [ 5 % ] in the placebo group ) and muscle-related adverse events ( ten patients [ 5 % ] vs 1 [ 1 % ] ) . INTERPRETATION In patients with heterozygous familial hypercholesterolaemia , evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60 % reductions in LDL cholesterol compared with placebo . FUNDING Amgen", "BACKGROUND Homozygous familial hypercholesterolaemia is a rare , serious disorder caused by very low or absent plasma clearance of LDL , substantially raised LDL cholesterol , and accelerated development of cardiovascular disease . Conventional lipid-lowering treatments are modestly effective . Evolocumab , a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) , reduced LDL cholesterol by 16 % in a pilot study . We now report results with evolocumab in a r and omised , double-blind , placebo-controlled phase 3 trial . METHODS This r and omised , double-blind , placebo-controlled phase 3 trial was undertaken at 17 sites in ten countries in North America , Europe , the Middle East , and South Africa . 50 eligible patients ( aged ≥12 years ) with homozygous familial hypercholesterolaemia , on stable lipid-regulating therapy for at least 4 weeks , and not receiving lipoprotein apheresis , were r and omly allocated by a computer-generated r and omisation sequence in a 2:1 ratio to receive subcutaneous evolocumab 420 mg or placebo every 4 weeks for 12 weeks . R and omisation was stratified by LDL cholesterol at screening ( computerised interactive voice-response system . Patients , study personnel , and the funder were masked to treatment and to the efficacy results by the central laboratory not returning LDL cholesterol or any lipid results to the clinical sites after the baseline visit . The primary endpoint was percentage change in ultracentrifugation LDL cholesterol from baseline at week 12 compared with placebo , analysed by intention-to-treat . This trial is registered with Clinical Trials.gov , number NCT01588496 . FINDINGS Of the 50 eligible patients r and omly assigned to the two treatment groups , 49 actually received the study drug and completed the study ( 16 in the placebo group and 33 in the evolocumab group ) . Compared with placebo , evolocumab significantly reduced ultracentrifugation LDL cholesterol at 12 weeks by 30·9 % ( 95 % CI -43·9 % to -18·0 % ; p events occurred in ten ( 63 % ) of 16 patients in the placebo group and 12 ( 36 % ) of 33 in the evolocumab group . No serious clinical or laboratory adverse events occurred , and no anti-evolocumab antibody development was detected during the study . INTERPRETATION In patients with homozygous familial hypercholesterolaemia receiving stable background lipid-lowering treatment and not on apheresis , evolocumab 420 mg administered every 4 weeks was well tolerated and significantly reduced LDL cholesterol compared with placebo . FUNDING Amgen", "Aim To evaluate the lipid‐lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus ( T2DM ) and hyperlipidaemia or mixed dyslipidaemia . Material s and methods BERSON was a double‐blind , 12‐week , phase 3 study ( NCT02662569 ) conducted in 10 countries . Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were r and omised 2:2:1:1 to evolocumab 140 mg every 2 weeks ( Q2W ) or 420 mg monthly ( QM ) or placebo Q2W or QM . Co‐ primary endpoints were the percentage change in low‐density lipoprotein cholesterol ( LDL‐C ) from baseline to week 12 and from baseline to the mean of weeks 10 and 12 . Additional endpoints included atherogenic lipids , glycaemic measures , and adverse events ( AEs ) . Results Overall , 981 patients were r and omised and received ≥1 dose of study drug . Evolocumab significantly reduced LDL‐C versus placebo at week 12 ( Q2W , −71.8 % ; QM , −74.9 % ) and at the mean of weeks 10 and 12 ( Q2W , −70.3 % ; QM , −70.0 % ; adjusted P atorvastatin . Non‐high‐density lipoprotein cholesterol , apolipoprotein B100 , total cholesterol , lipoprotein ( a ) , triglycerides , high‐density lipoprotein cholesterol , and very low‐density lipoprotein cholesterol improved significantly with evolocumab versus placebo . The overall incidence of AEs was similar between evolocumab and placebo‐treated patients , and there were no clinical ly meaningful differences in changes over time in glycaemic variables ( fasting serum glucose and HbA1c ) between the two groups . Conclusions In patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin , evolocumab significantly reduced LDL‐C and other atherogenic lipids , was well tolerated , and had no notable impact on glycaemic measures ", "Aims /hypothesisThe study aim ed to examine the efficacy of 12 weeks of monthly evolocumab or placebo in lowering LDL-cholesterol ( LDL-C ) in individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia and on a maximum-tolerated statin of at least moderate intensity . Methods For this r and omised , placebo-controlled outpatient study , eligible individuals were ≥18 years old with type 2 diabetes , HbA1c Lipid eligibility criteria varied by history of clinical cardiovascular disease . Participants were r and omised 2:1 to evolocumab 420 mg s.c . or placebo . R and omisation was performed central ly via an interactive web-based or voice recognition system . Allocation was concealed using the central ised r and omisation process . Treatment assignment was blinded to the sponsor study team , investigators , site staff and patients throughout the study . Co- primary endpoints were mean percentage change in LDL-C from baseline to week 12 and to the mean of weeks 10 and 12 . Additional endpoints included LDL-C . Exploratory analyses included percentage changes in fasting and post mixed-meal tolerance test ( MMTT ) lipoproteins and lipids , glucose metabolism variables and inflammatory biomarkers . Results In total , 421 individuals were r and omised and analysed , having received evolocumab ( 280 participants ) or placebo ( 141 participants ) ( mean [ SD ] age 62 [ 8 ] years ; 44 % women ; 77 % white ) . Evolocumab decreased LDL-C by 54.3 % ( 1.4 % ) at week 12 ( vs 1.1 % [ 1.9 % ] decrease with placebo ; p also decreased non-HDL-cholesterol ( HDL-C ) by 46.9 % ( 1.3 % ) at week 12 ( vs 0.6 % [ 1.8 % ] decrease with placebo ) and by 56.6 % ( 1.2 % ) at the mean of weeks 10 and 12 ( vs 0.1 % [ 1.6 % ] decrease with placebo ) . Evolocumab significantly improved levels of other lipids and allowed more participants to reach LDL-C LDL-C levels ≥50 % . After an MMTT ( 120 min ) , there were favourable changes ( p in chylomicron triacylglycerol ( triglycerides ) , chylomicron cholesterol , VLDL-C and LDL-C. Evolocumab had no effect on glycaemic variables and was well tolerated . Conclusions /interpretationIn statin-treated individuals with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia , evolocumab significantly reduced LDL-C and non-HDL-C. Favourable changes ( p of chylomicrons , VLDL-C and LDL-C.Trial registration Clinical Trials.gov NCT02739984 Funding This study was funded by Amgen Inc. Data availabilityQualified research ers may request data from Amgen clinical studies . Complete details are available at www.amgen.com/ data sharing", "Importance Reducing levels of low-density lipoprotein cholesterol ( LDL-C ) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels . Proprotein convertase subtilisin kexin type 9 ( PCSK9 ) inhibitors produce incremental LDL-C lowering in statin-treated patients ; however , the effects of these drugs on coronary atherosclerosis have not been evaluated . Objective To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients . Design , Setting , and Participants The GLAGOV multicenter , double-blind , placebo-controlled , r and omized clinical trial ( enrollment May 3 , 2013 , to January 12 , 2015 ) conducted at 197 academic and community hospitals in North America , Europe , South America , Asia , Australia , and South Africa and enrolling 968 patients presenting for coronary angiography . Interventions Participants with angiographic coronary disease were r and omized to receive monthly evolocumab ( 420 mg ) ( n = 484 ) or placebo ( n = 484 ) via subcutaneous injection for 76 weeks , in addition to statins . Main Outcomes and Measures The primary efficacy measure was the nominal change in percent atheroma volume ( PAV ) from baseline to week 78 , measured by serial intravascular ultrasonography ( IVUS ) imaging . Secondary efficacy measures were nominal change in normalized total atheroma volume ( TAV ) and percentage of patients demonstrating plaque regression . Safety and tolerability were also evaluated . Results Among the 968 treated patients ( mean age , 59.8 years [ SD , 9.2 ] ; 269 [ 27.8 % ] women ; mean LDL-C level , 92.5 mg/dL [ SD , 27.2 ] ) , 846 had evaluable imaging at follow-up . Compared with placebo , the evolocumab group achieved lower mean , time-weighted LDL-C levels ( 93.0 vs 36.6 mg/dL ; difference , -56.5 mg/dL [ 95 % CI , -59.7 to -53.4 ] ; P PAV , increased 0.05 % with placebo and decreased 0.95 % with evolocumab ( difference , -1.0 % [ 95 % CI , -1.8 % to -0.64 % ] ; P evolocumab ( difference , -4.9 mm3 [ 95 % CI , -7.3 to -2.5 ] ; P . Evolocumab induced plaque regression in a greater percentage of patients than placebo ( 64.3 % vs 47.3 % ; difference , 17.0 % [ 95 % CI , 10.4 % to 23.6 % ] ; P patients with angiographic coronary disease treated with statins , addition of evolocumab , compared with placebo , result ed in a greater decrease in PAV after 76 weeks of treatment . Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes . Trial Registration clinical trials.gov Identifier : NCT01813422", "BACKGROUND Bococizumab , a humanized monoclonal antibody targeting proprotein convertase subtilisin – kexin type 9 ( PCSK9 ) , reduces levels of low‐density lipoprotein ( LDL ) cholesterol . However , the variability and durability of this effect are uncertain . METHODS We conducted six parallel , multinational lipid‐lowering trials enrolling 4300 patients with hyperlipidemia who were r and omly assigned to receive 150 mg of bococizumab or placebo subcutaneously every 2 weeks and who were followed for up to 12 months ; 96 % were receiving statin therapy at the time of enrollment . The patients were assessed for lipid changes over time , stratified according to the presence or absence of antidrug antibodies detected during the treatment period . RESULTS At 12 weeks , patients who received bococizumab had a reduction of 54.2 % in the LDL cholesterol level from baseline , as compared with an increase of 1.0 % among those who received placebo ( absolute between‐group difference , ‐55.2 percentage points ) . Significant between‐group differences were also observed in total cholesterol , non – high‐density lipoprotein cholesterol , apolipoprotein B , and lipoprotein(a ) ( P high‐titer antidrug antibodies developed in a substantial proportion of the patients who received bococizumab , which markedly diminished the magnitude and durability of the reduction in LDL cholesterol levels . In addition , among patients with no antidrug antibodies , there was wide variability in the reduction in LDL cholesterol levels at both 12 weeks and 52 weeks . Major cardiovascular events occurred in 57 patients ( 2.5 % ) who received bococizumab and in 55 ( 2.7 % ) who received placebo ( hazard ratio , 0.96 ; 95 % confidence interval , 0.66 to 1.39 ; P=0.83 ) . The most common adverse event among patients who received bococizumab was injection‐site reaction ( 12.7 per 100 person‐years ) . CONCLUSIONS In six multinational trials evaluating bococizumab , antidrug antibodies developed in a large proportion of the patients and significantly attenuated the lowering of LDL cholesterol levels . Wide variation in the relative reduction in cholesterol levels was also observed among patients in whom antidrug antibodies did not develop . ( Funded by Pfizer ; SPIRE Clinical Trials.gov numbers , NCT01968954 , NCT01968967 , NCT01968980 , NCT02100514 , NCT02135029 , and NCT02458287 .", "BACKGROUND Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin – kexin type 9 ( PCSK9 ) and reduces levels of low‐density lipoprotein ( LDL ) cholesterol . We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk . METHODS In two parallel , multinational trials with different entry criteria for LDL cholesterol levels , we r and omly assigned the 27,438 patients in the combined trials to receive bococizumab ( at a dose of 150 mg ) subcutaneously every 2 weeks or placebo . The primary end point was nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for unstable angina requiring urgent revascularization , or cardiovascular death ; 93 % of the patients were receiving statin therapy at baseline . The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies , as seen in data from other studies in the program . The median follow‐up was 10 months . RESULTS At 14 weeks , patients in the combined trials had a mean change from baseline in LDL cholesterol levels of ‐56.0 % in the bococizumab group and + 2.9 % in the placebo group , for a between‐group difference of –59.0 percentage points ( P baseline LDL cholesterol level of ≥70 mg per deciliter [ 1.8 mmol per liter ] and the median follow‐up was 7 months ) , major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group ( hazard ratio , 0.99 ; 95 % confidence interval [ CI ] , 0.80 to 1.22 ; P=0.94 ) . In the higher‐risk , longer‐ duration trial ( in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [ 2.6 mmol per liter ] and the median follow‐up was 12 months ) , major cardiovascular events occurred in 179 and 224 patients , respectively ( hazard ratio , 0.79 ; 95 % CI , 0.65 to 0.97 ; P=0.02 ) . The hazard ratio for the primary end point in the combined trials was 0.88 ( 95 % CI , 0.76 to 1.02 ; P=0.08 ) . Injection‐site reactions were more common in the bococizumab group than in the placebo group ( 10.4 % vs. 1.3 % , P respect to major adverse cardiovascular events in the trial involving lower‐risk patients but did have a significant benefit in the trial involving higher‐risk patients . ( Funded by Pfizer ; SPIRE‐1 and SPIRE‐2 Clinical Trials.gov numbers , NCT01975376 and NCT01975389 .", "BACKGROUND Alirocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 , has been shown to provide significant reductions in low-density lipoprotein cholesterol ( LDL-C ) . Data about its efficacy and safety in patients from South Korea and Taiwan are limited . OBJECTIVE ODYSSEY KT assessed the efficacy and safety of alirocumab in patients from South Korea and Taiwan . METHODS Patients with hypercholesterolemia at high cardiovascular risk who were on maximally tolerated statin were r and omized ( 1:1 ) to alirocumab ( 75 mg every 2 weeks , with dose increase to 150 mg every 2 weeks at week 12 if LDL-C ≥70 mg/dL at week 8) or placebo for 24 weeks . The primary efficacy endpoint was percentage change in LDL-C from baseline to week 24 . Safety was assessed throughout . RESULTS At week 24 , alirocumab changed LDL-C levels by -57.1 % ( placebo : + 6.3 % ) . In the alirocumab group , 9 patients ( 9.5 % ) received dose increase at week 12 . At week 24 , 85.8 % of patients in the alirocumab group reached LDL-C ) . Alirocumab significantly improved non-high-density lipoprotein cholesterol ( non-HDL-C ) , apolipoprotein B , total cholesterol , lipoprotein ( a ) , and HDL-C vs placebo ( P ≤ .05 ) . Two consecutive calculated LDL-C values of alirocumab-treated patients . Overall , 58.8 % ( alirocumab ) and 61.8 % ( placebo ) of patients experienced treatment-emergent adverse events ; 2.1 % and 1.0 % discontinued treatment due to treatment-emergent adverse events , respectively . CONCLUSION Alirocumab significantly improved LDL-C , apolipoprotein B , non-HDL-C , lipoprotein ( a ) , HDL-C , and total cholesterol in Asian patients . Alirocumab was generally well tolerated . These findings are consistent with ODYSSEY findings to date", "BACKGROUND : Patients with heterozygous familial hypercholesterolemia ( FH ) and coronary heart disease have high mortality rates . However , in an era of high-dose statin prescription after acute coronary syndrome ( ACS ) , the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated . We compared coronary event rates between patients with and without FH after ACS . METHODS : We studied 4534 patients with ACS enrolled in a multicenter , prospect i ve cohort study in Switzerl and between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions : the American Heart Association definition , the Simon Broome definition , and the Dutch Lipid Clinic definition . We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infa rct ion and adjusted for age , sex , body mass index , smoking , hypertension , diabetes mellitus , existing cardiovascular disease , high-dose statin at discharge , attendance at cardiac rehabilitation , and the GRACE ( Global Registry of Acute Coronary Events ) risk score for severity of ACS . RESULTS : At the 1-year follow-up , 153 patients ( 3.4 % ) had died , including 104 ( 2.3 % ) of fatal myocardial infa rct ion . A further 113 patients ( 2.5 % ) experienced nonfatal myocardial infa rct ion . The prevalence of FH was 2.5 % with the American Heart Association definition , 5.5 % with the Simon Broome definition , and 1.6 % with the Dutch Lipid Clinic definition . Compared with patients without FH , the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses , although patients with FH were > 10 years younger . However , after multivariable adjustment including age , the risk was greater in patients with FH than without , with an adjusted hazard ratio of 2.46 ( 95 % confidence interval , 1.07–5.65 ; P=0.034 ) for the American Heart Association definition , 2.73 ( 95 % confidence interval , 1.46–5.11 ; P=0.002 ) for the Simon Broome definition , and 3.53 ( 95 % confidence interval , 1.26–9.94 ; P=0.017 ) for the Dutch Lipid Clinic definition . Depending on which clinical definition of FH was used , between 94.5 % and 99.1 % of patients with FH were discharged on statins and between 74.0 % and 82.3 % on high-dose statins . CONCLUSIONS : Patients with FH and ACS have a > 2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins" ]	41184d3e-06ff-11f0-808a-c43d1ab1c353
Background Both minimally invasive surgery ( MIS ) and computer-assisted surgery ( CAS ) for total hip arthroplasty ( THA ) have gained popularity in recent years . We conducted a qualitative and systematic review to assess the effectiveness of MIS , CAS and computer-assisted MIS for THA . Methods An extensive computerised literature search of PubMed , Medline , Embase and OVIDSP was conducted . Both r and omised clinical trials and controlled clinical trials on the effectiveness of MIS , CAS and computer-assisted MIS for THA were included . Method ological quality was independently assessed by two review ers . Effect estimates were calculated and a best- evidence synthesis was performed . Results Four high- quality and 14 medium- quality studies with MIS THA as study contrast , and three high- quality and four medium- quality studies with CAS THA as study contrast were included . No studies with computer-assisted MIS for THA as study contrast were identified . Strong evidence was found for a decrease in operative time and intraoperative blood loss for MIS THA , with no difference in complication rates and risk for acetabular outliers . Strong evidence exists that there is no difference in physical functioning , measured either by question naires or by gait analysis . Moderate evidence was found for a shorter length of hospital stay after MIS THA . Conflicting evidence was found for a positive effect of MIS THA on pain in the early postoperative period , but that effect diminished after three months postoperatively . Strong evidence was found for an increase in operative time for CAS THA , and limited evidence was found for a decrease in intraoperative blood loss . Furthermore , strong evidence was found for no difference in complication rates , as well as for a significantly lower risk for acetabular outliers . Conclusions The results indicate that MIS THA is a safe surgical procedure , without increases in operative time , blood loss , operative complication rates and component malposition rates . However , the beneficial effect of MIS THA on functional recovery has to be proven . The results also indicate that CAS THA , though result ing in an increase in operative time , may have a positive effect on operative blood loss and operative complication rates . More importantly , the use of CAS results in better positioning of acetabular component of the prosthesis	[ "Implant malposition and poor fixation are potential risks of compromising long-term results after total hip arthroplasty performed with a minimally invasive technique . Between September 2000 and February 2002 , 120 cemented primary total hip arthroplasties were performed at the authors ' institutions in patients with primary osteoarthritis of the hip and with BMI lower than 35 . In 60 of these cases selected at r and om , a posterolateral incision no longer than 10 cm was used . The other 60 THA 's were performed through a st and ard posterolateral approach . The inclination and anteversion of the cup and the position of the femoral stem were assessed on radiographs and statistically evaluated . In the miniinvasive group , the average inclination angle of the cup was 42.3 degrees ( range : 36 to 52 degrees ) and the anteversion angle 13.6 degrees ( range : 6 to 29 degrees ) . The coronal alignment of the femoral component was within 3 degrees of neutral in 54 cases ( 90.0 % ) . Following conventional implantation in the other group , the average cup inclination angle was 42.4 degrees ( range : 35 to 50 degrees ) and the anteversion angle 13.6 degrees ( range : 8 to 24 degrees . A total of 53 stems ( 88.3 % ) were implanted optimally . Statistical analysis found no significant difference between the two groups regarding components position . These findings suggest that using a smaller posterolateral incision as was done in this study does not introduce a potential risk of compromising long-term results", "BACKGROUND AIMS Evaluation of : 1 . early clinical and radiographic results of total hip arthroplasty ( THA ) through a st and ard lateral direct approach , 2 . early clinical and radiographic results of THA through a minimal lateral approach , 3 . comparison of the results of THA in these two groups . MATERIAL AND METHODS 120 THAs ( 60 cementless and 60 cemented ) done in 120 patients due to degenerative changes were evaluated prospect ively . 60 THAs were done through a minimal lateral approach and constituted a study group . 60 THAs were done through a direct lateral approach and constituted a control group . The mean age of the 120 patients ( 98 women and 22 men ) was 45 y.o . ( range : 32 - 67 y.o . ) . The duration of follow-up in the study group was from 6 to 12 months ( mean : 8.5 months ) . The duration of follow-up in the control group was from 10 to 16 months ( mean : 10.5 months ) . Mean preoperative functional status of the study group was 44.5 points according to the Harris hip score . Radiographic evaluation of the results was done according to the criteria of the Joint Committee of the Hip Society , AAOS and SICOT . RESULTS 6 months after THA , clinical results were 92 pts in the study group and 88 pts in the control group . Radiographic outcomes were very good in all 120 patients from both arms : there were no differences between the control and study group . The incidence of complications was similar in both groups . CONCLUSIONS Minimally invasive THA demonstrated its value in the treatment of degenerative changes of the hip joint with regard to short-term outcomes . The clinical and radiographic outcomes were comparable between the st and ard and minimally invasive approaches . Success with THA using a minimally invasive approach depends on excellent operative technique and experience with st and ard hip approaches rather than on the use of special instruments", "In a prospect i ve and r and omised clinical study , acetabular cups were implanted free-h and ( control group n=22 ) or with computer assistance using an image-free navigation system ( study group n=23 ) . The cup position was determined postoperatively on pelvic CT . An average inclination of 42.3 ° ( range : 30 ° –53 ° ; SD±7.0 ° ) and an average anteversion of 24.0 ° ( range : −3 ° to 51 ° ; SD±15.0 ° ) were found in the control group , and an average inclination of 45.0 ° ( ranage : 40 ° –50 ° ; SD±2.8 ° ) and an average anteversion of 14.4 ° ( range : 5 ° –25 ° ; SS±5.0 ° ) in the computer-assisted study group . The deviations from the desired cup position ( 45 ° inclination , 15 ° anteversion ) were significantly lower in the computer-assisted study group ( p cupules acétabulaires ont été implantées de façon habituelle ( n=22 ; groupe témoin ) ou avec assistance d’un ordinateur qui utilise un système de navigation image — libre ( n=23 ; groupe d’étude ) . La place de la cupule a été déterminée après l’opération sur un scanner pelvien . Une inclinaison moyenne de 42,3 ° ( 30 ° à 53 ° ; ±7.0 ° ) et une antéversion moyenne de 24,0 ° ( −3 ° à 51 ° ; ±15.0 ° ) ont été trouvées dans le groupe témoin et une inclinaison moyenne de 45,0 ° ( 40 ° à 50 ° ; ±2.8 ° ) et une antéversion moyenne de 14,4 ° ( 5 ° à 25 ° ; ±5.0 ° ) dans le groupe de l’étude assistée par ordinateur . Les déviations par rapport à la position désirée de la cupule ( 45 ° d’inclinaison , 15 ° d’antéversion ) étaient notablement inférieures dans le groupe de l’étude assistée par ordinateur ( p<0.001 chacun ) . Alors que seulement 11 des 22 cupules du groupe témoin étaient dans la zone sûre de Lewinnek , 21 des 23 cupules du groupe d’étude ont été placées dans cette région cible ( p=0.003 )", "Background The Levels of Evidence Rating System is widely believed to categorize studies by quality , with Level I studies representing the highest quality evidence . We aim ed to determine the reporting quality of R and omised Controlled Trials ( RCTs ) published in the most frequently cited general orthopaedic journals . Methods Two assessors identified orthopaedic journals that reported a level of evidence rating in their abstract s from January 2003 to December 2004 by search ing the instructions for authors of the highest impact general orthopaedic journals . Based upon a priori eligibility criteria , two assessors h and search ed all issues of the eligible journal from 2003–2004 for RCTs . The assessors extracted the demographic information and the evidence rating from each included RCT and scored the quality of reporting using the reporting quality assessment tool , which was developed by the Cochrane Bone , Joint and Muscle Trauma Group . Scores were conducted in duplicate , and we reached a consensus for any disagreements . We examined the correlation between the level of evidence rating and the Cochrane reporting quality score . Results We found that only the Journal of Bone and Joint Surgery – American Volume ( JBJS-A ) used a level of evidence rating from 2003 to 2004 . We identified 938 publications in the JBJS-A from January 2003 to December 2004 . Of these publications , 32 ( 3.4 % ) were RCTs that fit the inclusion criteria . The 32 RCTs included a total of 3543 patients , with sample sizes ranging from 17 to 514 patients . Despite being labelled as the highest level of evidence ( Level 1 and Level II evidence ) , these studies had low Cochrane reporting quality scores among individual method ological safeguards . The Cochrane reporting quality scores did not differ significantly between Level I and Level II studies . Correlations varied from 0.0 to 0.2 across the 12 items of the Cochrane reporting quality assessment tool ( p > 0.05 ) . Among items closely corresponding to the Levels of Evidence Rating System criteria assessors achieved substantial agreement ( ICC = 0.80 , 95%CI:0.60 to 0.90 ) . Conclusion Our findings suggest that readers should not assume that 1 ) studies labelled as Level I have high reporting quality and 2 ) Level I studies have better reporting quality than Level II studies . One should address method ological safeguards individually", "BACKGROUND Minimally invasive total hip arthroplasty has stirred substantial controversy with regard to whether it provides superior outcomes compared with total hip arthroplasty performed through longer incisions . The orthopaedic literature is deficient in well- design ed scientific studies to support the clinical superiority of this approach . The objective of this study was to compare the results of a single mini-incision approach with those of a st and ard-incision total hip arthroplasty in the early postoperative period . METHODS Two hundred and nineteen patients ( 219 hips ) admitted for unilateral total hip arthroplasty between December 2003 and June 2004 were r and omized to undergo surgery through a short incision of All patients were blinded to the size of the incision for the duration of the hospital stay . The anesthetic , analgesic , and postoperative physiotherapy protocol s were st and ardized , with the staff also blinded to the technique used . A single surgeon , who had performed more than 300 short-incision hip replacements prior to the start of this study and who performs an average of 415 primary total hip replacements a year , performed all procedures through a single-incision posterior approach using a cementless cup and cemented stem . RESULTS The two groups were matched for age , grade according to the system of the American Society of Anesthesiologists , and body mass index . No significant difference was detected with respect to postoperative hematocrit , blood transfusion requirements , pain scores , or analgesic use . We found no difference in early walking ability or length of hospital stay and no difference in component placement , cement-mantle quality , or functional outcome scores at six weeks . The patient variables significantly associated with a probability of early discharge independent of incision length were patient age and preoperative hemoglobin levels ( p surgical scars contracted significantly over six weeks ( p single-incision posterior approach by a high-volume hip surgeon with extensive experience in less invasive approaches to the hip is safe and reproducible . However , it offers no significant benefit in the early postoperative period compared with a st and ard incision of 16 cm . As it is not known whether lower-volume and less-experienced surgeons can achieve similar results , the mini-incision technique merits further study before wide dissemination and implementation of this family of surgical approaches can be recommended", "The version of the acetabular and femoral components in 111 primary total hip arthroplasties was prospect ively evaluated intraoperatively by the surgeon and compared with postoperative computed tomography ( CT ) scan measurements . Intraoperative estimations by the surgeons for acetabular and femoral components were all within 10 degrees to 30 degrees anteversion , with means of 16.0 degrees ( SD = 4.0 degrees ) and 16.4 degrees ( SD = 3.2 degrees ) , respectively . However , CT scan acetabular measurements ranged from 12 degrees retroversion to 52 degrees anteversion ( mean = 22.0 degrees anteversion , SD = 14.0 degrees ) . Similarly , femoral component version ranged from -15 degrees retroversion to 45 degrees anteversion ( mean = 16.8 degrees anteversion , SD = 11.1 degrees ) . According to CT calculations , only 71 % of femoral and 45 % of acetabular components were within the expected clinical version range . In conclusion , the intraoperative estimation of acetabular and femoral version in a total hip arthroplasty is of limited accuracy", "This study examined the effect of the surgical approach used in total hip arthroplasty ( THA ) on gait mechanics six months following surgery . Quantitative gait analysis was performed on 29 subjects : 10 anterolateral ( A-L ) and 10 posterolateral ( P-L ) THA patients and nine able-bodied , velocity-matched subjects . Discriminant function analysis was used to determine the distinction of the groups with respect to sagittal plane hip range of motion , index of symmetry , trunk inclination , pelvic drop , hip abduction , and foot progression angles . The A-L group had the largest trunk inclination ( 3.0+/-2.4 degrees ) and the smallest hip range of motion ( 34.0+/-7.4 degrees ) . Both THA groups demonstrated greater asymmetry as expressed by the smaller symmetry index ( 0.97+/-0.04 for A-L and 0.98+/-0.05 for the P-L ) than the able-bodied group ( 0.99+/-0.01 ) . The classification procedure correctly classified 89 % of the control group cases , 90 % of the A-L cases , and 50 % of the P-L cases . These results support the conclusion that six months following surgery , the gait of the majority ( 85 % ) of THA patients has not returned to normal . The A-L patients displayed distinct gait patterns , while a small percentage ( 30 % ) of the P-L patients demonstrated normal gait . While these differences are statistically significant , the clinical significance is unknown and linked to the duration that they persist", "Introduction Advantages of minimally invasive total hip arthroplasty ( THA ) are controversially discussed . Method In this prospect i ve study 51 patients ( 52 hips ) were r and omly allocated to a classical lateral or a minimally invasive approach ( modification of the Hardinge-approach ) . Operating time , intraoperative blood loss , postoperative hemoglobin , muscle enzymes CK and myoglobin were recorded . Radiologically the positioning of the prosthesis was analyzed . WOMAC- and Harris Hip Score ( HHS ) were assessed preoperatively , at discharge , at 6 weeks and 3 months . Results In the minimally invasive group there was a shorter length of surgery , the scores in the WOMAC and HHS were slightly better at discharge and at the 3 months- examination , myoglobin-rise was slightly less . The positioning of the prosthesis was good in both groups . Minimally invasive THA led to a quicker recovery , at 3 months postoperative there was still a slight difference to the st and ard group . Conclusion If these slight differences subside has to be examined in studies with a longer follow-up", "OBJECTIVES To study responsiveness and establish the minimal clinical ly important differences ( MCID ) and minimal detectable change ( MDC ) in patients undergoing total hip replacement ( THR ) using the Short Form 36 ( SF-36 ) and the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . METHODS We conducted a prospect i ve observational study in three public hospitals of all consecutive patients with a diagnosis of hip osteoarthritis ( OA ) on waiting lists to undergo THR . Patients completed the SF-36 and the WOMAC ( subscales transformed to 0 to 100 ) , which measured the health-related quality of life ( HRQoL ) , before intervention and 6 months and 2 years later , and additional transitional questions , which measured the changes in the joint 6 months postoperatively . RESULTS Improvements at 6 months after a THR were between 37 ( stiffness ) and 39 points ( pain ) , depending on the WOMAC domain . The SF-36 domains also showed improvements : physical function ( 31.91 ) , physical role ( 33.71 ) , and bodily pain ( 29.77 ) . From 6 months to 2 years , improvements ranged from 2 to 5 points , except for role physical ( 13.25 ) . A ceiling effect was detected on some WOMAC domains as well as a floor effect on the SF-36 . The MCID ranged from 25.91 ( stiffness ) to 29.26 ( pain ) on the WOMAC and from 10.78 ( physical role ) to 20.40 ( physical function ) on the SF-36 . The MDC ranged from 21.38 ( pain ) to 27.98 ( stiffness ) on the WOMAC and from 18.99 ( physical function ) to 42.05 ( social function ) on the SF-36 . CONCLUSIONS These values indicate expected gains after THR . However , the MCID and MDC values must be viewed cautiously due to the uncertainty of these estimators and should not be considered as absolute thresholds", "There has been little clinical research to examine the effects of patient positioning and pelvic motion on the alignment of the acetabular implant during total hip replacement surgery . Until now , no tools were capable of accurately measuring these variables during the actual procedure . As part of a broader program in medical robotics and computer assisted surgery , a clinical system has been developed that includes several enabling technologies . The hip navigation system ( HipNav ) continuously and precisely measures pelvic location and tracks relative implant alignment intraoperatively . HipNav technology is used to gauge current clinical practice and provide intraoperative feedback to surgeons with the goal of improving the precision and accuracy of acetabular alignment during total hip replacement . This system provides surgeons with a new class of image guided measurement tools and assist devices . These tools successfully were introduced into the clinical practice of surgery with results showing the following : ( 1 ) There exist unpredictable and large variations in the initial position of patients ' pelves on the operating room table and significant pelvic movement during surgery and during intraoperative range of motion testing ; ( 2 ) current mechanical acetabular alignment guides do not account for these variations , and result in variable and in the majority of cases unacceptable acetabular alignment ; and ( 3 ) press fitting oversized acetabular components influences the final cup orientation", "Objective : To compare responsiveness of the Harris Hip Score with generic measures ( that is , the Short Form-36 ( SF-36 ) , and a test of walking speed and pain during walking ) in patients with osteoarthritis ( OA ) of the hip . Method : The first 75 cases within the population of a r and omised clinical trial on manual therapy and exercise therapy were selected for secondary analysis . Experienced ( self reported ) recovery by the patients after treatment ( five weeks ) was used as an external criterion for clinical ly relevant improvement . Responsiveness was evaluated by comparing responsiveness ratios and receiver operating characteristic curves . Results : The responsiveness ratio for the Harris Hip Score was high ( 1.70 ) compared with walking speed ( 0.45 ) , pain during walking ( 0.66 ) , and the subscales of the SF-36—“bodily pain ” ( 0.42 ) and “ physical functioning ” ( 0.36 ) . The area under the curve also was highest for the Harris Hip Score ( 0.92 ) compared with walking speed ( 0.71 ) , pain during walking ( 0.73 ) , and the SF-36 subscales — bodily pain and physical functioning ( both 0.66 ) . Conclusion : The Harris Hip Score is more responsive than the test of walking speed , pain , and subscales for function of the SF-36 in patients with OA of the hip . The Harris Hip Score seems to be a suitable instrument to evaluate change in hip function in patients with OA of the hip", "Surgical approaches to the hip for total hip arthroplasty ( THA ) are termed minimally invasive when allowing for a skin incision length of 10 cm or less . The aim of this study was to explore if a minimally invasive posterior approach compared to a classic anterolateral approach negatively influenced surgical time , blood loss , implant position , or perioperative complications . Two groups of THA patients mainly differing with respect to the surgical approach were compared . Results of 76 consecutive THA via a posterior mini-incision approach were recorded prospect ively and those of 76 controls operated via a classic anterolateral approach were recorded retrospectively . THA was performed by the same surgeon in every case . Surgical time or intraoperative blood loss were not different among the groups . Total 24-h blood loss was significantly less in patients undergoing THA via minimally invasive posterior approaches . Median cup inclination was 45 degrees in both groups . Cup anteversion was 15 degrees ( classic anterolateral ) and 12 degrees ( minimally invasive posterior ) , respectively . Stem position was regarded as neutral in 80 % of THA through classic anterolateral and in 76 % through minimally invasive dorsal incisions . Complications occurred in 8 % ( classic anterolateral ) and 9 % ( minimally invasive posterior ) of THA patients . Surgical time , blood loss , risk of malpositioned implants , or complications were not increased for THA patients operated through minimally invasive posterior incisions compared to those operated via classic anterolateral approaches", "In a prospect i ve r and omised clinical study acetabular components were implanted either freeh and ( n = 30 ) or using CT-based ( n = 30 ) or imageless navigation ( n = 30 ) . The position of the component was determined post-operatively on CT scans of the pelvis . Following conventional freeh and placement of the acetabular component , only 14 of the 30 were within the safe zone as defined by Lewinnek et al ( 40 degrees inclination sd 10 degrees ; 15 degrees anteversion sd 10 degrees ) . After computer-assisted navigation 25 of 30 acetabular components ( CT-based ) and 28 of 30 components ( imageless ) were positioned within this limit ( overall p significant reduction in variation of the position of the acetabular component compared with conventional freeh and arthroplasty ( p duration of the operation was increased by eight minutes with imageless and by 17 minutes with CT-based navigation . Imageless navigation proved as reliable as that using CT in positioning the acetabular component", "BACKGROUND Malpositioning of the acetabular component during total hip arthroplasty increases the risk of dislocation , reduces the range of motion , and can be responsible for early wear and loosening . The purpose of this study was to compare computer-assisted with freeh and insertion of the acetabular component . METHODS A r and omized , controlled , matched prospect i ve study of two groups of thirty patients each was performed . In the first group , cup positioning was assisted by an imageless computer-assisted surgical system based on bone morphing . In the control group , the cup was placed freeh and . All of the patients were operated on by the same surgeon through an anterolateral approach . Cup anteversion and abduction angles were measured on three-dimensional computed tomography reconstructions postoperatively for each patient by an independent observer using special cup-evaluation software . RESULTS There were sixteen men and fourteen women in each group , and the mean body-mass index was approximately 25 in each group . The computer-assisted procedure took a mean of twelve minutes longer than the freeh and procedure . Fifty-seven percent ( seventeen ) of the thirty cups placed freeh and and 20 % ( six ) of the thirty in the computer-assisted group were outside of the defined safe zone ( outliers ) . This difference was significant ( p = 0.002 ) . There were no differences between the computer-assisted group and the freeh and -placement group with regard to the mean abduction and anteversion angles , but there was a significant heterogeneity of variances , with the lowest variations in the computer-assisted group . CONCLUSIONS Use of an imageless navigation system can improve cup positioning in total hip arthroplasty by reducing the percentage of outliers", "Optimal orientation of the acetabular component of a total hip prosthesis is an important factor in determining the early and long-term result of a total hip arthroplasty ( THA ) . Conventional positioning of the cup component is usually done using a free-h and method , or with the help of a mechanical acetabular alignment guide . However , these methods have proven to be inaccurate , and a great variation in orientation of the cup is found postoperatively . In this study , we wished to determine if the variability of the abduction angle of acetabular cups could be reduced with the use of computer navigation . The abduction angles of the acetabular components of three groups of 50 THAs were assessed . In the first group , a free-h and method was used to position the cup component . This group was operated in the period before we started using computer navigation for hip surgery . In the second group , CT-based computer navigation was used to plan and help position the cup . The third group consisted of 50 THA cases in which a free-h and method was used to position the cup , although these procedures were performed in the period after we had begun using the Computer Assisted Surgery ( CAS ) system . The variability in cup abduction angle was assessed in all three groups and compared . There was a significant reduction in variability in the CAS group compared to the first group . There was also a reduction in variability in the CAS group compared to the third group , although this was not statistically significant . It is concluded that the use of computer navigation helped the surgeon to place the cup component with less variability of the abduction angle , and , more importantly , we found that no cups were placed in the more extreme positions ( outliers )", "Minimally invasive ( MI ) total hip replacement ( THR ) supposedly provides improved ambulation in the immediate post-operative period . This study used a prospect i ve blinded design to analyse early post-operative walking ability using gait analysis . Seventeen patients were available for full analysis with nine having had the MI technique and eight having the st and ard incision ( SI ) technique . Patients were blinded as to the incision used , as were all physiotherapists and assessors . Differences in temporal-spatial variables and joint kinematics measured 1 day pre-operatively , 2 days post-operatively and 42 days ( 6 weeks ) post-operatively were compared between groups . There was no significant difference in velocity , step length of the affected or unaffected leg , stride length or stance phase duration between the MI and SI groups between any of the timepoints tested . There was no significant improvement in the gait kinematics of the MI group compared to the SI group either 2 days post-operatively or 6 weeks post-operatively . Contrary to previous studies , there was no improvement in early post-operative gait for those patients who received THR using the minimally invasive technique", "Objective : To compare the results of single-incision minimally invasive total hip replacement ( ≤ 10 cm ) to st and ard-incision ( 16 cm ) total hip replacement in the early postoperative period with respect to functional and mobilizing ability ( transfers , mobilizing , walking and stair assessment ) . Setting : Orthopaedic wards of a regional orthopaedic centre . Subjects : Two hundred and nineteen total hip replacement patients were tested between December 2003 and June 2004 . Interventions : Patients were r and omized to either total hip replacement through a minimally invasive ( ≤ 10 cm ) or st and ard incision ( 16 cm ) . A single surgeon performed all procedures using the same type of component fixation . Postoperative physiotherapy assessment and treatment was st and ardized . Analgesia was also st and ardized . All patients , physiotherapy staff and assessors were blinded to the incision used . Main outcome measures : Patients were tested two days post operatively and were assessed for the following activities : transfer from supine to sit , transfer from sitting to st and ing , mobilizing , ascending and descending stairs and weight-bearing . Results : The shorter incision offered no significant improvement in patient ability in relation to transfer from lying to sitting , transfer from sitting to st and ing , mobilizing or weight-bearing . Ascending/descending stairs gave a total time for the minimal incision of 38.7 s against 40.8 s for a st and ard incision . There was no difference in walking velocity between the st and ard incision and minimal incision groups two days post operatively ( minimal incision = 0.26 m/s versus st and ard incision = 0.26 m/s ) or six weeks post operatively ( minimal incision = 0.90 m/s versus st and ard incision = 0.93 m/s ) . There was no difference between groups with respect to walking aids at six-week review . The mean length of stay for the minimally invasive approach was 3.65 days ( SD 2.04 ) against 3.68 days ( SD 2.45 ) for the st and ard approach . This was not significantly different . Conclusion : Total hip replacement performed through a minimally invasive incision of ≤ 10 cm compared with a st and ard incision of 16 cm offers no significant benefit in terms of the rate or ability of patients to mobilize and perform functional tasks necessary for safe discharge ", "This prospect i ve study compares a mini-incision technique and traditional posterior approach for total hip arthroplasty ( THA ) . Thirty-three patients who had undergone a mini-incision THA were matched by diagnosis , gender , average age , and preoperative Harris Hip Score ( HHS ) to 33 patients who had undergone THA using the traditional posterior approach . The average length of the incision for group 1 was 11.7 cm ( range , 7.3 - 13.0 ) and for group 2 was 20.2 cm ( range , 14.8 - 26.0 ) . At the 3-month follow-up , patients in the mini-incision group had significant improvement in limp ( P ability to climb stairs ( P mini-incision group was significantly better in terms of limp ( P distance walked ( P stairs ( P pain , function , or range of motion at the 1-year follow-up examination", "The purpose of this prospect i ve r and omized study was to compare the early results of primary total hip arthroplasties performed with a minimally invasive technique or a st and ard technique . A consecutive series of 70 patients who underwent primary bilateral simultaneous total hip arthroplasties was studied . All procedures were performed through a posterolateral approach . Operative times and duration of hemovac drains were significantly shorter in the group with a minimally invasive technique ( P risk of infection when using this technique . There were no any late transfusions in any of our patients postdischarge . This minimally invasive technique did not offer any advantages because the results were not different , and in our h and s , it increased our infection rate", "Patients without prior hip surgery and body mass index lower than 30 undergoing primary total hip arthroplasty were eligible to participate in a r and omized prospect i ve study comparing a minimally invasive with a st and ard approach . The patients were r and omized to receive incisions of 8 cm ( group A , n = 28 ) or 15 cm ( group B , n = 32 ) . The groups were similar demographically . Patients in group A had significantly less intraoperative blood loss ( P total blood loss ( P Operative time , transfusion requirements , narcotic usage , length of hospital stay , achievement of rehabilitation milestones , cane usage , and complications were similar in both groups . There was no difference between the groups at 1- and 2-year follow-up . Compared with a st and ard incision , patients who underwent a minimally invasive total hip arthroplasty demonstrated decreased blood loss and limped less at 6-week follow-up", "BACKGROUND Few prospect i ve r and omized studies have demonstrated benefits of minimally invasive total hip arthroplasty when compared with conventional total hip arthroplasty . We hypothesized that patients treated with a posterior mini-incision would have better results than those treated with a posterior long incision with regard to the achievement of established goals for pain relief and functional recovery permitting hospital discharge by the second postoperative day . METHODS Sixty of 231 eligible patients were r and omized ( with thirty in each group ) to have a total hip arthroplasty performed through either a posterior mini-incision ( 10 + /- 2 cm ) or a traditional long incision ( 20 + /- 2 cm ) . After completion of the total hip arthroplasty , the mini-incision group underwent extension of the skin incision to 20 cm . Patients were evaluated on the basis of self-determined pain scores , requirements for pain medicine , need for assistive gait devices , and time until discharge . Gait analysis provided objective functional assessment . RESULTS The average hospital stay was 63.2 + /- 13.3 hours in the mini-incision group and 73.6 + /- 23.5 hours in the long-incision group ( p = 0.04 ) . More patients with a mini-incision were discharged by the second postoperative day ( p = 0.003 ) and more were using just a single assistive device at the time of discharge ( p = 0.005 ) . As scored on a verbal analog scale of 0 to 10 points , patients with a mini-incision had less pain on each postoperative day and the pain score remained significantly lower at the time of discharge ( mean , 2.2 + /- 1.0 points compared with 3.1 + /- 0.9 points in the long-incision group ; p = 0.002 ) . After hospital discharge , there were no clinical differences in pain or function between the two groups of patients . CONCLUSIONS Compared with conventional total hip arthroplasty performed through a posterior incision , posterior minimally invasive total hip arthroplasty result ed in better early pain control , earlier discharge to home , and less use of assistive devices . Subsequent evaluations at six weeks and three months showed equivalency between the clinical results in the two groups . LEVEL OF EVIDENCE Therapeutic Level", "Abstract Despite the high number of total hip arthroplasty ( THA ) procedures performed each year , there is no common consensus on the best surgical approach . Gait is known to improve following THA although it does not return to what is typically quantified as normal , and surgical approach is believed to be a contributing factor . The current study evaluates post-operative hip function and provides an objective assessment following two common surgical approaches : the McFarl and —Osborne direct lateral and the southern posterior . Faced with the common problem of providing an objective comparison from the wealth of data collected using motion analysis techniques , the current study investigates the application of an objective classification tool to provide information on the effectiveness of each surgery and to differentiate between the characteristics of hip function following the two approaches . Seven inputs for the classifier were determined through statistical analysis of the biomechanical data . The posterior approach group exhibited greater characteristics of non-pathological gait and displayed a greater range of functional ability as compared with the lateral approach cohort . The classification tool has proved to be successful in characterizing non-pathological and THA function but was insufficient in distinguishing between the two surgical cohorts" ]	41184dc0-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Various hormone therapies ( HT ) are available to treat menopausal vasomotor symptoms . Bioidentical hormones are chemically identical to those produced by the human body , and several types are well-tested and available on prescription . Many women have opted for bioidentical hormone therapy ( BHT ) on the assumption that it is safer than other forms of HT . We evaluated the evidence . OBJECTIVES To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms . SEARCH METHODS In July 2015 we search ed the Cochrane Central Register of Controlled Trials , PubMed , Embase , Literatura Latino-Americana e do Caribe em Ciências da Saúde ( LILACS ) , registers of ongoing trials and the reference lists of articles retrieved . SELECTION CRITERIA R and omised controlled trials ( RCTs ) comparing bioidentical hormone therapy ( BHT ) versus placebo or non-bioidentical hormones . DATA COLLECTION AND ANALYSIS We used st and ard method ological procedures expected by the Cochrane Collaboration . Our primary outcome was vasomotor symptoms ( hot flushes and night sweats ) . We evaluated the overall quality of the evidence using Grading of Recommendations Assessment , Development and Evaluation criteria ( GRADE ) . MAIN RESULTS We included 23 RCTs ( 5779 participants ) . Most studies ( 20/23 ) included only women with moderate to severe hot flushes . All studies compared unopposed 17 beta-estradiol ( beta-estradiol ) versus placebo or conjugated equine estrogens ( CEE ) . None of the studies reported night sweats as a separate outcome . BHT patch versus placebo Frequency of hot flushesFour RCTs reported data suitable for analysis . There were fewer hot flushes in the BHT group , with a moderate to large effect size ( SMD -0.68 , 95 % CI -0.83 to -0.53 , four RCTs , 793 women , I(2 ) = 67 % , low quality evidence ) . There was moderate heterogeneity , but a consistent direction of effect . Seven RCTs reported data unsuitable for analysis ; all reported a benefit in the intervention group . Symptom intensityTwo RCTs reported analysable data . Measured on a 0 - 100 visual analogue scale ( VAS ) , hot flush intensity was lower in the BHT group ( MD -19.94 points , 95 % CI -24.86 to -15.02 , two RCTs , 393 women , I(2 ) = 54 % , low quality evidence ) . There was moderate heterogeneity , but a consistent direction of effect . Adverse effectsAdverse events ( such as headache , vaginal bleeding , breast tenderness and skin reactions ) were more common in the intervention group ( odds ratio ( OR ) 2.14 , 95 % CI 1.29 to 3.54 , 9 RCTs , 1822 women , I(2 ) = 73 % , low quality evidence ) . There was moderate heterogeneity , but a consistent direction of effect . In one study , five women in the intervention group developed endometrial hyperplasia . BHT gel versus placebo Hot flush frequencyThree RCTs reported this outcome , but the data were unsuitable for analysis . All reported a benefit in the BHT group . Adverse effectsAdverse events were more common in the BHT group ( OR 1.41 , 95 % CI 1.09 to 1.83 , 3 RCTs , 1086 women , I(2 ) = 0 % , moderate quality evidence ) . Oral BHT versus placebo Hot flush frequencyTwo studies reported analysable data . There were fewer hot flushes in the BHT group , with a moderate to large effect size ( SMD -0.80 , 95 % CI -1.03 to -0.57 , two RCTs , 356 women , I(2 ) = 14 % , low quality evidence ) . Adverse effectsThere was no evidence of a difference between the groups ( OR 1.28 , 95 % CI 0.84 to 1.96 , 3 RCTs , 433 women , I(2 ) = 0 % , low quality evidence ) . Topical BHT emulsion versus placebo Hot flush frequencyOne study with data unsuitable for analysis reported a benefit in the intervention group . Adverse effectsThere was no evidence of a difference between the groups ( OR 1.46 , 95 % CI 0.80 to 2.66 , one RCT , 200 women , low quality evidence ) . Intranasal BHT versus placebo Hot flush frequencyOnly one study reported analysable data . There were fewer hot flushes per day in the BHT group ( MD -3.04 95 % CI -4.05 to -2.03 , one study , 458 women , moderate quality evidence ) Adverse effectsAdverse events ( such as headache , breast tenderness , arthralgia and nausea ) were more common in the intervention group ( OR 1.96 , 95 % CI 1.26 to 3.03 , one RCT , 458 women , moderate quality evidence ) . Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects . BHT patch versus 0.625 mg CEETwo RCTs reported this comparison , but the data were unsuitable for analysis . Hot flush frequencyBoth RCTs reported no evidence of a difference between the groups . Adverse effects Findings were inconsistent . In one comparison ( 0.1 mg BHT versus CEE ) , breast pain and vaginal bleeding were more frequent in the BHT group . Oral BHT versus 0.625 mg CEE Hot flush frequencyOne study with data unsuitable for analysis reported no evidence of a difference between the groups . Adverse effectsThere was no evidence of a difference between the groups ( OR 1.20 , 95 % CI 0.50 to 2.87 , one RCT , 103 women , very low quality evidence ) . AUTHORS ' CONCLUSIONS There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes . There was low to moderate quality evidence of higher rates of adverse effects such as headache , vaginal bleeding , breast tenderness and skin reactions in the BHT group . There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects . Although all the included studies used unopposed estrogen , it is recommended best practice to use progestogen therapy in women with a uterus taking estrogen in order to avoid endometrial hyperplasia , regardless of the source of the estrogen . No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack , stroke and breast cancer . There was no good evidence of a difference in effectiveness between BHT and CEE , and findings with regard to adverse effects were inconsistent . The quality of the evidence was too low to reach any firm conclusions .The main limitations in the quality of the evidence were study risk of bias ( mainly due to poor reporting of methods ) , imprecision and lack of data suitable for analysis	[ "Twenty-six postmenopausal women participated in a double-blind trial involving treatment according to a Latin square design with either ( i ) dl-norgestrel alone ( 0.075 mg/day ) continuously for two cycles , ( ii ) estradiol-17 beta alone ( 1 mg on 25 of 28 days ) for two cycles , or ( iii ) the combined hormones for six cycles . A placebo control cycle followed each hormonal treatment . Plasma triglycerides decreased by an average 22 % during treatment with either dl-norgestrel alone ( 123 + /- 11 vs. 160 + /- 10 mg/dl , n = 25 , P Plasma total cholesterol fell by 5 % during two cycles of treatment with either dl-norgestrel alone ( 229 + /- 11 vs. 242 + /- 10 mg/dl , n = 25 , P free of flushing ( vs. 31 % for control , P free of spotting not requiring protection ( control 75 % ) , 96 % of cycles were free of vaginal bleeding ( control 100 % ) , endometrial biopsy showed inactive endometrium in nine of the 10 subjects re-biopsied , fasting blood pyruvate decreased by 20 % ( P diastolic blood pressure fell by 4 % compared with control ( P glucose tolerance was unchanged . There was a significant reduction in vasomotor flushing beginning with the third to fourth cycles of combination therapy", "New estradiol ( E2 ) transdermal matrix patches developed for once-a-week application , releasing 25 μg E2 ( 7D-25 ) or 50 μg E2 ( 7D-50 ) daily , were investigated in comparison with a placebo patch and the twice-weekly parent patch releasing 50 μg E2 ( Derm-50 ) daily . Three hundred and eleven postmenopausal patients suffering at least seven hot flushes daily were r and omly assigned to the four parallel groups and treated continuously for 12 weeks without progestin opposition . The daily number of hot flushes significantly decreased in all groups . At the 12th week the decrease from a baseline average of eight to nine episodes per day was 78 % with 7D-25 , 93 % and 97 % respectively with 7D-50 and Derm-50 , and significantly ( p in terms of severity of hot flushes , Kupperman Index and patient self-rated overall efficacy . Minor systemic adverse events occurred in 10.0 % , 8.8 % , 16.9 % ) and 13.5 % patients in the placebo , 7D-25 , 7D-50 and Derm-50 groups respectively . Occasional mild and transient itching and /or erythema at the site of application was reported by a few patients , with no difference between groups or between once-weekly or twice-weekly application . In conclusion all E2 patches were significantly more effective than placebo in relieving climacteric symptoms in a dose-dependent fashion and all were well tolerated", "Background For postmenopausal women , the main reason to start hormone therapy ( HT ) is to reduce menopausal symptoms and to improve quality of life ( QOL ) . The aim of this study was to analyse the impact of HT on different aspects of symptom experience and QOL during a r and omised trial . A total of 1823 postmenopausal women were recruited into the Estonian Postmenopausal Hormone Therapy ( EPHT ) trial in 1999–2001 . Women were r and omised to blind HT , open-label HT , placebo or non-treatment arm . After one year in the trial , a question naire was mailed and 1359 women ( 75 % ) responded , 686 in the HT arms and 673 in the non-HT arms . Mean age at filling in the question naire was 59.8years . The question naire included Women 's Health Question naire ( WHQ ) to assess menopause specific QOL of middle-aged women together with a 17-item question naire on symptoms related to menopause , a question about painful intercourse , and a question about women 's self-rated health . Results After one year in the trial , fewer women in the HT arms reported hot flashes , trouble sleeping , and sweating on the symptom question naire . According to WHQ , women in the HT arms had fewer vasomotor symptoms , sleep problems , and problems with sexual behaviour , but more menstrual symptoms ; HT had no effect on depression , somatic symptoms , memory , attractiveness , or anxiety . A smaller proportion of women reported painful intercourse in the HT arms . There were no significant differences between the trial arms in women ’s self-rated subjective health . Conclusions The results from the EPHT trial confirm that HT is not justified for treating symptoms , other than vasomotor symptoms , among postmenopausal women . WHQ proved to be a useful and sensitive tool to assess QOL in this age group of women", "OBJECTIVES We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate ( MPA ) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infa rct ion , or both . BACKGROUND Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women ; however , women with an intact uterus also take progestin to protect against uterine malignancies . The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown . METHODS Eighteen postmenopausal women ( mean + /- SD age 59+/-7 years ) were given 17-beta-estradiol in single-blinded manner for four weeks ( 1 mg/day for three weeks then 2 mg/day for one week ) . Estradiol ( 2 mg/day ) was then continued , and the patients were r and omized ( double-blind ) for 12 days to either transvaginal progesterone gel ( 90 mg on alternate days ) and oral MPA placebo ( 10 mg/day ) , or vice versa . After another two weeks on estradiol alone , the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment . Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase . RESULTS Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline ( mean difference with 95 % confidence interval [ CI ] : 72 s [ 34 to 110 ] , p = 0.001 ) , and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy ( 92 s [ 35 to 149 ] , p = 0.001 ) ) . Two patients ( 11 % ) were withdrawn while taking estradiol/MPA owing to unstable angina . CONCLUSIONS Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia , as compared with estrogen/MPA . These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration", "The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid , pregnanolone , before and during different hormonal setting s of postmenopausal hormone replacement therapy ( HRT ) , using natural progesterone . A second aim was to investigate whether the response to pregnanolone was associated with cyclicity in negative mood symptoms during treatment . Twenty six postmenopausal women with climacteric symptoms were administered HRT in a r and omized , double blinded , placebo-controlled , crossover study . The women received 2 mg oral estradiol ( E(2 ) ) continuously during two 28-day cycles and 800 mg of vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle . Pharmacodynamic response to pregnanolone was assessed before treatment , and during the last week of each treatment cycle , by comparing the effects of intravenous pregnanolone ( 3alpha-hydroxy-5beta-pregnan-20-one ) on saccadic eye velocity ( SEV ) , saccade acceleration , saccade latency and self-rated sedation . Throughout the study daily symptom rating scales were kept . According to the daily symptom rating scales , patients were divided into two groups ; one group who displayed a significant variance in negative mood symptoms during HRT ( cyclicity ) and one group with no cyclical changes in negative mood symptoms during treatment . During treatment with either E(2 ) alone or E(2)+progesterone the response in saccadic eye movement parameters and in self-rated sedation to pregnanolone was enhanced compared to pretreatment values . The SEV , saccade acceleration and sedation responses to pregnanolone was also increased in women expressing cyclicity in negative mood symptoms compared to women with no cyclical changes in negative mood during HRT . In conclusion , during treatment with either E(2 ) alone , or E(2)+progesterone , pregnanolone sensitivity was increased . Women expressing cyclicity in negative mood symptoms were more sensitive to pregnanolone than women without symptom cyclicity during HRT", "Objective To evaluate the efficacy of two ultra-low-dose 17β-estradiol plus norethisterone acetate ( NETA ) treatment regimens for relieving menopausal symptoms . Design A total of 577 postmenopausal women were enrolled , in three treatment groups in a double-blind , r and omized , placebo-controlled study of 0.5 mg 17β-estradiol + 0.1 mg NETA or 0.5 mg 17β-estradiol + 0.25 mg NETA or placebo . Participants returned at weeks 4 , 8 , 12 and 24 for climacteric complaint evaluation based on a daily diary vasomotor symptom record . Patients were assessed by the Greene Climacteric Scale and urogenital symptoms were also evaluated . Results Treatment with ultra-low-dose 0.5 mg 17β-estradiol + 0.1 mg NETA ( 0.1 Group ) or 0.5 mg 17β-estradiol + 0.25 mg NETA ( 0.25 Group ) effectively reduced the severity and number of hot flushes within the initial weeks of therapy . Compared to placebo , a rapid , statistically significant decrease in the frequency and severity of hot flushes was achieved by week 3 , followed by further improvement which continued throughout the study . There were no statistically significant differences between the active treatment arms . Conclusions The data show that both ultra-low-dose regimens are effective in reducing the severity and number of hot flushes compared to placebo , with good safety profiles", "Objectives To investigate two different doses of oral estradiol to reduce the number of hot flushes in Japanese women with climacteric symptoms . Methods Women ( n = 211 ) aged 40–64 years who had experienced natural menopause or bilateral oophorectomy , with ≥ three moderate/severe hot flushes per day in the week before study , were r and omized to receive micronized estradiol ( E2 ) 0.5 or 1.0 mg or placebo once daily for 8 weeks . The primary efficacy endpoint was percentage change in mean daily number of hot flushes over 7 days from baseline to final examination . Results Percentage change in mean daily number of hot flushes at final examination was similar for E2 0.5 mg and E2 1.0 mg ( −79.58 ± 28.29 % vs. −82.49 ± 25.31 % , p = 0.555 ) but was significantly lower with placebo ( −57.89 ± 34.15 % , p significant difference in number of treatment-related adverse events occurring in the E2 0.5 and 1.0 mg groups ( 25 % and 36.6 % , respectively ) . The higher E2 dose showed more pronounced effects on symptom severity . Conclusions The dose of 0.5 mg/day was effective as the oral E2 starting dose for treatment of hot flushes in Japanese women", "Abstract Objective : To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone ( P ) parental monthly formulations using novel non-polymeric microspheres . Methods : This was a multicenter , r and omized , single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P ( Group A , n = 34 ) , 1 mg E + 20 mg P ( Group B , n = 24 ) or 1 mg E + 30 mg P ( Group C , n = 26 ) for 6 months . Primary efficacy endpoints included mean change in the frequency and severity of hot flushes and the effect over urogenital atrophy symptoms at 3 and 6 months . Safety variables included changes in the rate of amenorrhea , endometrial thickness and histopathology , and local and systemic adverse events . Results : Compared to baseline at month 6 , the three treatment schemes significantly decreased the rate of urogenital atrophy symptoms and the frequency ( mean number per day ) and severity ( mean number grade d as moderate and severe per month ) of hot flushes . No differences in studied efficacy parameters were observed between studied groups at baseline or at the end of the study . For all groups the most frequent adverse event was pain at the injection site ; however they were all rated as mild . At the end of the study peri- and postmenopausal women displayed no significant changes in endometrial thickness or histopathology in all treated groups . The rate of amenorrhea at the end of the study decreased for all studied groups yet was less evident among postmenopausal women as compared to perimenopausal ones . Conclusions : The three low-dose continuous sequential intramuscular monthly treatments of E/P using novel microsphere technology were effective at reducing menopausal symptoms at short-term with a low rate of adverse events . More long-term and comparative research is warranted to support our positive findings", "Two estradiol ( E2 ) transdermal patches releasing 25 micrograms/day E2 ( D-25 ) or 37.5 micrograms/day E2 ( D-37.5 ) were compared to a placebo patch on 156 patients in natural or surgical menopause suffering from at least 5 hot flushes per day , r and omly and blindly assigned to three parallel groups of 52 patients each , to be treated continuously for 12 weeks , without progestin opposition . \" Responders \" ( patients with less than 3 hot flushes per day at the end of treatment ) , were 82 % and 90 % under D-25 or D-37.5 , respectively , both significantly ( p placebo ( 44 % ) . Comparable efficacy was observed on severity of hot flushes , Kupperman Index and on the self-rated efficacy . Systemic adverse events occurred in 10 % , 10 % and 8 % of patients , respectively , under D-25 , D-37.5 or placebo . Occasional mild and transient itching and /or erythema on the site of application was reported by few patients and did never require discontinuation of application . In conclusion D-25 and D-37.5 were significantly more effective than placebo in relieving climacteric symptoms and were systemically and locally as well tolerated as placebo . D-25 ( Demestril 25 ) releasing 25 micrograms/day E2 can therefore be recommended for low-dosed estrogen replacement therapy", "Acute menopausal symptoms occur less frequently in Asian than in Caucasian women . Oestrogen replacement therapy has been shown to be effective in controlling acute symptoms in Caucasians , but the effect of oestrogens is not well documented in Asian women . A r and omized , double-blind , placebo-controlled , crossover study of the effect of oral oestradiol on the incidence of acute menopausal symptoms was conducted in 83 Hong Kong Chinese women who had experienced a surgical menopause . Although there was a significant increase in the oestradiol concentration with treatment compared with placebo ( P reporting of symptoms between the treatment and placebo groups . There is no obvious explanation for this apparent lack of effect of oestrogen on acute menopausal symptoms in Chinese women . Whilst it may be related to the generally low incidence of symptoms or to a higher dietary intake of phytoestrogens in Chinese women , further studies are necessary to explain these findings", "INTRODUCTION Recent clinical trials have caused physicians to reconsider the use of hormone therapy ( HT ) . Low-dose therapy has been proposed for those patients who tolerate st and ard doses poorly . OBJECTIVE to evaluate low-dose and ultra low-dose estrogen therapy ( ET ) for vasomotor symptom control . MATERIAL S AND METHOD Thirty five healthy postmenopausal women with moderate to severe climacteric symptoms were recruited . Symptoms were evaluated at baseline and three months after the beginning of treatment by a modified Kupperman 's index ( KI ) . Endometrial thickness was assessed with pelvic ultrasonography . Patients were r and omly assigned to one of these therapies : I ) Esterified conjugated estrogens ( ECE ) 0.156 mg/day ( ultra low-dose ) ( n = 18 ) or II ) ECE 0.312 mg/day ( low-dose ) ( n = 17 ) for 12 weeks . Statistical analysis was done with student 's t test for independent and paired sample s. RESULTS In groups I and II , the ab and on rate was 33.3 % and 47.0 % , respectively . No differences were found among the groups in general data nor in KI . The KI at the end of the study was 47.8+/-37.9 and 48.9+/-33.2 for group I and group II , respectively , for a mean decrease of 32.1 % and 37 % without differences between the groups . When comparing each group separately , KI decreased in group 1 , but without statistical significance . In group II there was significant decrease in KI . Endometrial thickness increased from 2.5+/-1.0 to 4.2+/-1.7 mm in group I , and from 3.5+/-1.3 to 6.0 + /-1.4 mm in group II . CONCLUSION low dose and ultra-low dose ET were useful in decreasing climacteric symptoms", "Objectives To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms . Design Multicenter , double-blind , r and omized , placebo-controlled study . Results Of 165 subjects r and omized to estradiol 0.014 mg/day or placebo for 12 weeks , 80 per group were included in the analysis . Groups were comparable at baseline , although time since menopause was slightly shorter in the estradiol group . There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group ( 55 % ) than the placebo group ( 40 % ; p moderate and severe hot flushes ( −58 % vs. −39 % , respectively ) . Reductions were statistically significant at weeks 4 , 8 , and 12 . Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period , but there were no significant changes in the placebo group . Vaginal maturation value increased more in the estradiol than the placebo group ( p had vaginal bleeding or spotting . Quality of life improved similarly in both groups . Urogenital symptoms improved considerably from baseline in both treatment groups , with no significant differences . Eight subjects experienced treatment-related adverse events ( seven in the estradiol group ) . Conclusions In Asian women , micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms . The bleeding profile was comparable with that of placebo . Micro-dose estradiol was safe and well tolerated in Asian women", "OBJECTIVE To assess if regular physical exercise or oral oestradiol therapy decreased vasomotor symptoms and increased quality of life in previously sedentary postmenopausal women . SETTING A prospect i ve , r and omised trial at a University Hospital . METHODS 75 postmenopausal , sedentary women with vasomotor symptoms were r and omised to : exercise three-times weekly over 12 weeks ( 15 women ) , oral oestradiol therapy for 12 weeks ( 15 women ) and 45 women to three other treatment arms . Results from the exercise and oestradiol groups are presented here . The effects on vasomotor symptoms and wellbeing were assessed with logbooks and vali date d question naires . RESULTS Ten women fulfilled 12 weeks of exercise . The number of flushes was rather unchanged in five women and decreased to 28 % ( range 18 - 42 % ) of baseline in the other five women . Five of the ten women continued to exercise another 24 weeks , thus in all 36 weeks . The mean number of flushes decreased by about 50 % in these five women ( from 6.2/24 to 3.2 flushes/24 h at 36 weeks ) . In the same group a score made as the product of reduction in number and severity of flushes decreased by 92 % at 12 weeks , 75 % at 24 weeks and 72 % at 36 weeks compared with baseline . In the estrogen group flushes decreased from 8.4 to 0.8 ( P Well-being according to different measurements improved significantly in both groups , albeit more markedly in the estrogen group . CONCLUSIONS Apart from many other health benefits regular physical exercise may decrease vasomotor symptoms and increase quality of life in postmenopausal women , but this has to be further evaluated scientifically . Exercise should be introduced gradually to ensure compliance", "Objectives : To evaluate the efficacy and safety of different doses of 17&bgr;‐estradiol for the treatment of vasomotor and vulvovaginal symptoms . Design : This was a r and omized , double‐blind , multicenter , parallel‐group study . One hundred forty‐five subjects , including naturally postmenopausal women aged 40‐60 ( who had not experienced menses for at least 12 months ) , women who had undergone hysterectomy , and women aged 25‐60 who had undergone bilateral oophorectomy with or without hysterectomy were studied . Either placebo or 17&bgr;‐estradiol ( 1 mg or 0.5 mg ) was given orally every day for 12 weeks , and vasomotor symptoms and vaginal epithelial cytology were evaluated . Results : There were significant differences between placebo and the active treatments in the percentage change from baseline in the number of hot flushes ( all hot flushes , 1 mg vs. placebo , p mean number of hot flushes of 83.2 % ) . Both doses were also more effective than placebo in increasing the proportion of mature vaginal cells ( end‐of‐treatment mean values of 0 % , 78.5 % , and 21.5 % for parabasal , intermediate , and superficial cells , respectively , in the 1‐mg group ; mean values of 0.3 % , 80.8 % , and 18.9 % in the 0.5‐mg group ; and mean values of 15.2 % , 74.7 % , and 10.2 % in the placebo group ) . The proportion of subjects reporting no vaginal dryness was greatest in the 1‐mg group ( mean percentage of days without dryness of 86.1 % at weeks 9‐12 ) . Conclusions : For the relief of vasomotor and vulvovaginal symptoms , 17&bgr;‐estradiol 1 mg is effective and has an excellent safety profile . ( Menopause 2000;7:310‐317 . © 2000 , The North American Menopause Society .", "OBJECTIVE : To investigate the safety and efficacy of a transdermal estradiol ( E2 ) spray in women with postmenopausal vasomotor symptoms . METHOD : A r and omized , double-blind , placebo-controlled , multicenter , parallel-group clinical trial was conducted . Postmenopausal women ( N=454 ) with at least eight moderate-to-severe hot flushes per day applied daily , one , two , or three E2 ( 90 microliter spray contains 1.53 mg E2 ) or matching placebo sprays . The primary efficacy endpoints were mean change from baseline in frequency and severity of moderate-to-severe hot flushes at weeks 4 and 12 . RESULTS : All three E2 groups showed a significant decrease in hot flushes at weeks 4 and 12 compared with their placebo groups ( P mean change in frequency at week 12 was eight fewer flushes per day for women in the E2 groups and between four and six fewer flushes for women in the placebo groups . Women in the three- and two-E2 spray groups demonstrated significant ( P reductions in severity score at weeks 4 and 12 ; women in the one-spray group showed significant reductions at week 5 . At week 12 , the majority ( 74–85 % ) of women on E2 showed at least a 50 % hot flush frequency reduction as compared with 46 % in the placebo group . The systemic E2 delivery rates at week 12 were approximately 0.021 mg/d , 0.029 mg/d , and 0.040 mg/d for the one- , two- , and three-spray doses , respectively . Common adverse events were similar to those previously reported with other transdermal products . Treatment-related application site reaction rate was similar to placebo ( 1.3 % compared with 1.8 % ) . CONCLUSION : The three dose levels of E2 spray achieved efficacy at 0.021–0.040 mg/d delivery rates . The spray is a well-tolerated , new , convenient method of delivering low-dose E2 transdermally . Clinical Trial Registration : Clinical Trials.gov , www . clinical trials.gov , NCT00122200 LEVEL OF EVIDENCE :", "Objective To determine the efficacy and tolerability of two strengths of percutaneous 17&bgr;-estradiol in a hydroalcoholic gel and placebo in controlling vasomotor symptoms of menopause . Design A total of 221 postmenopausal women were assigned r and omly to treatment with percutaneous 17&bgr;-estradiol gel 1.25 g ( containing 0.75 mg of estradiol ) or 2.5 g ( containing 1.5 mg of estradiol ) or placebo gel applied once daily for 12 weeks . The primary efficacy variable was the mean change from baseline in the frequency of moderate/severe hot flushes . In addition , the mean changes from baseline in the frequency and severity of all hot flushes were assessed . Safety and tolerability were evaluated from endometrial biopsy , adverse events , and laboratory tests . Results A significant reduction ( P mean frequency of moderate-to-severe hot flushes and mean frequency and severity of all hot flushes was observed with both 17&bgr;-estradiol gel groups compared with placebo . The mean number of moderate-to-severe hot flushes at the end of the study with 17&bgr;-estradiol gel 2.5 g , 17&bgr;-estradiol gel 1.25 g , and placebo gel was 2.0 , 2.8 and 5.2 , respectively . The overall incidence of adverse events was not significantly different among groups , though a higher incidence of estrogen-related adverse events was reported with the 17&bgr;-estradiol gel 2.5-g dose . Conclusions 17&bgr;-estradiol gel was effective and well tolerated for alleviating moderate-to-severe hot flushes in postmenopausal women . Therapy may be initiated with the 1.25-g dose with an increase to the 2.5-g dose if needed", "Objective : To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system ( lipophilic emulsion-type base ) to relieve climacteric symptoms . The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern . Design : An open , r and omized , comparative , between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments . Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months . Pharmacokinetic data following transdermal administration of 17β-estradiol ( 0.3 mg , daily ) and progesterone ( 100 mg , daily ) were calculated from saliva levels using high-performance liquid chromatography analysis . Results : Improvement in climacteric symptoms was reported in 93 % of women evaluated before and after 3 and 6 months of treatment . Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL , and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders , 88 % characterized symptom relief as complete . No adverse health-related events were attributed to the bioidentical hormone therapy . Time to maximum saliva concentrations ( Tmax ) , in all experimental cases , was observed after 6 hours . Baseline values were reached within 24 hours , indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period , ie , its daily biological rhythm . Conclusion : Percutaneous absorption of 17β-estradiol , as well as the absorption of progesterone , was associated with relief of climacteric symptoms . The cyclical transdermal delivery of combined bioidentical hormones may be advantageous because it mimics the secretory profiles of 17β-estradiol and progesterone in normally cyclic women over a 28-day period . Larger studies are needed to determine the long-term effects of our therapy", "This study reports the clinical effects in a group of post-menopausal women after 4 months of treatment with 2 mg micronized 17 beta-oestradiol ( E2 ) in combination with different doses of micronized progesterone ( 50 , 100 or 200 mg ) for 25 days each month . The 30 participants were divided into three groups . All of the subjects tolerated the preparation well and obtained relief from their climacteric complaints . None dropped out because of side effects and no changes were observed in blood pressure , weight or Papanicolaou cytology . Breakthrough bleeding was noted in the first cycle , mainly in the group receiving the lowest dose of progesterone . Endometrial biopsies performed before and after 4 months of treatment showed an atrophic endometrium in most of the women who received 100 mg progesterone and in all of the women on 200 mg progesterone . The results showed that this new combination of 2 mg E2 and micronized progesterone in different doses was both effective and well accepted ", "BACKGROUND Pulsed estrogen therapy is a new approach in estrogen replacement therapy . We carried out a prospect i ve study to evaluate the efficacy of pulsed estrogen therapy in relatively younger patients with surgically induced menopause . METHODS Patients ( n=138 ) After the initiation of pulsed estrogen therapy ( 300 microg/day ) , the patients were re-evaluated every 4 weeks . The dose was increased at each follow-up , if necessary ( to a maximum of 600 microg/day ) . The patients who preferred another method after the first 12 weeks were prescribed oral conjugated estrogen ( 0.625 mg/day ) and at the end of the second 12 weeks their satisfaction levels were assessed . RESULTS At the end of the first 12 weeks , 26 patients were completely satisfied ( 18.8 % ) and 47 were moderately satisfied ( 34.1 % ) , whereas 65 concluded that the pulsed estrogen therapy they received was ineffective ( 47.1 % ) . At the end of the second 12 weeks , all the patients were completely satisfied . CONCLUSION Pulsed estrogen therapy for 12 weeks reduced the frequency of hot flushes in relatively younger patients with surgically induced menopause ; however , 81.2 % of patients were not completely satisfied at the end of this period", "Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms . Treatment was with either 2 mg 17 beta-oestradiol with 1 mg norethisterone acetate [ E2 + NETA ] ; 2 mg oestradiol valerate with 75 micrograms levonorgestrel [ E2V + LNG ] ; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [ E2V + MPA ] ; or 1.5 mg 17 beta-oestradiol with 150 micrograms desogestrel [ E2 + DG ] . A placebo-controlled study lasting 12 - 24 months was completed by 143 healthy early postmenopausal women . Bleeding lengths were not substantially different ; in all regimens the majority of women were bleeding for 3 - 6 days . Bleeding onset showed differences when related to the 11th day of progestogen addition ; in the regimen with E2V + LNG , 21 % of the women women were bleeding before the 11th day of progestogen addition 26 % on , and 53 % after that day . In the regimen with E2V + MPA , 56 % of the women were bleeding before the 11th day , 28 % on , and 17 % after that day , whereas in the regimen with E2 + DG , 15 % of the women were bleeding before the 11th day , 5 % on , and 80 % after that day . All regimens reduced climacteric symptoms to the same extent . Breast tenderness occurred in all the regimens , except in the E2 + DG . Conclusively , the differences between the responses to treatment were not conspicuous . However , our data indicate that one regimen ( E2 + DG ) result ed in optimal bleeding control , optimal effect on climacteric symptoms , and no production of breast tenderness", "CONTEXT Postmenopausal hormone therapy use increased dramatically during the past 2 decades because of a prevailing belief in its health benefits . Recent evidence from r and omized trials published in July 2002 demonstrated adverse cardiovascular disease events and other risks with hormone therapy in the form of oral estrogen combined with progestin . OBJECTIVE To describe patterns of hormone therapy use from 1995 until July 2003 , including the impact of recent evidence . DESIGN , SETTING , AND POPULATION Two data bases were used to describe national trends in hormone therapy use from January 1995 to July 2003 . The National Prescription Audit data base provided data on the number of hormone therapy prescriptions filled by retail pharmacies and the National Disease and Therapeutic Index data base provided data on patient visits to office-based physicians during which hormone therapy was prescribed . MAIN OUTCOME MEASURES Annual number of hormone therapy prescriptions and characteristics of visits to physicians during which hormone therapy was prescribed . RESULTS Annual hormone therapy prescriptions increased from 58 million in 1995 to 90 million in 1999 , representing approximately 15 million women per year , then remained stable through June 2002 . Adoption of new oral estrogen/progestin combinations , primarily Prempro , accounted for most of this growth . Obstetrician/gynecologists provided more than 70 % of hormone therapy prescriptions , and more than one third of patients were older than 60 years . Following the publication of trial results in July 2002 , hormone therapy prescriptions declined in successive months . Relative to January-June 2002 , prescriptions from January-June 2003 declined by 66 % for Prempro and 33 % for Premarin . Small increases were observed in vaginal formulations and in new prescriptions for low-dose Premarin . If prescription rates observed through July 2003 remain stable , a decline to 57 million prescriptions for 2003 , similar to the rate in 1995 , is projected . CONCLUSIONS Clinical practice responded rapidly to recent evidence of harms associated with hormone therapy . Since July 2002 , many patients have discontinued hormone therapy or are tapering to lower doses", "CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD", "OBJECTIVES To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch ( Fem7 , Merck KGaA , Germany ) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo . DESIGN A multicentre , r and omized , double-blind study with an initial screening phase ( phase I ) , a 3-month double-blind placebo-controlled phase ( phase II ) and a 3-month open follow-up phase ( phase III ) . METHODS 186 patients were r and omized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up ( total duration ; 6 months ) . The changes in Kupperman Index ( primary efficacy variable ) , hot flushes and urogenital symptom score were studied from baseline to the end of the study . In addition , skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy . RESULTS A reduction in Kupperman Index was observed in both groups , and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo ( last value vs. baseline P = 0.0006 ) . From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group . The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase ( mean weekly hot flush reduction at the end of the placebo-controlled treatment phase : -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo , P = 0.0025 ) . The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1 - 3 and 4 - 7 . Subjective acceptance of the 7-day-Estradiol patch was good and 72.4 % of patients who took active medication throughout the study were willing to consider continuing its use . CONCLUSIONS The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women , with a rapid onset of action and 7-day duration of therapeutic effect . Although a placebo effect was observed , the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period", "OBJECTIVE To examine the efficacy and tolerability of a new matrix patch delivering estradiol ( E2 Matrix ) at doses of 0.05 and 0.10 mg per day ( Estraderm MX 50 , 100 ) in the treatment of moderate to severe postmenopausal symptoms . METHODS A total of 254 postmenopausal women were r and omized to receive treatment with E2 Matrix 0.10 mg ( N = 86 ) , E2 Matrix 0.05 mg ( N = 82 ) , or placebo ( N = 86 ) in a double-blind , double-dummy fashion for a period of 12 weeks continuously . Patches were applied twice weekly to the buttocks with each patient wearing two patches at all times . The primary efficacy criterion was the difference from baseline of the mean number of moderate to severe hot flushes per 24 h during the last 2 weeks of treatment . Other efficacy variables included reduction in hot flushes at 4 and 8 weeks , reduction in daytime flushing and night sweats , and Kupperman Index at 4 , 8 , and 12 weeks . RESULTS E2 Matrix 0.10 and 0.05 mg were both significantly superior to placebo in reducing hot flushes per 24 h after 4 , 8 , and 12 weeks of treatment ( P efficacy parameters studied , both dosage strengths of E2 Matrix were statistically significantly superior to placebo at all time points ( P Local tolerability was good in both groups . A slight increase in estrogen related adverse effects ( breast tenderness , leukorrhoea ) was seen with the 0.10 mg patch . Adhesion of patches and compliance were good . Overall systemic tolerability was good in both treated groups . However , a 4.8 % overall incidence of endometrial hyperplasia was observed in patients with an intact uterus . CONCLUSIONS This new matrix patch offers an effective and well tolerated dosage form for delivery of 0.05 and 0.1 mg estradiol per day . It may be particularly suitable for those women who experience local sensitivity to alcohol-containing systems . In light of the observed hyperplasia after treatment in five patients , estrogen therapy should as yet be supplemented monthly with a progestogen in women with an intact uterus", "OBJECTIVE The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a r and omized trial over 12 weeks . STUDY DESIGN Two hundred forty-two women were r and omized , and 223 were analyzed for efficacy ( n = 112 for estradiol and n = 111 for placebo ) . The quality of life was assessed by means of a battery of st and ard question naires . RESULTS Quality of life improved after both therapies , but health-related quality of life ( p = 0.0003 ) and well being ( p = 0.003 ) improved more after transdermal estradiol therapy than after placebo . This was also the case for all specific climacteric aspects , including sexual problems ( p dysfunction ( p = 0.01 ) , at comparison with placebo . Self-rated symptom relief was more pronounced with estrogen therapy than with placebo ( p estradiol therapy was superior to placebo in relieving symptoms and improving quality of life", "OBJECTIVE To assess the efficacy and safety of 17-beta estradiol buccal tablets in reducing hot flush frequency ( HFF ) in postmenopausal women . METHODS Estradiol buccal tablets containing 0.05 , 0.1 , 0.2 , or 0.4 mg or placebo were administered for 28 days to 99 postmenopausal women in a r and omized , double-blind study ; 19 premenopausal women were studied concurrently for comparison of laboratory data . Objective and subjective assessment s of HFF were obtained along with measures of estradiol , estrone , follicle-stimulating hormone ( FSH ) , and luteinizing hormone ( LH ) . RESULTS Measurements of HFF revealed significant decreases from baseline in all estradiol groups ( P HFF decreased significantly compared to placebo ( P estradiol doses produced similar improvement in the vaginal maturation index . Mean serum estradiol levels increased as doses increased but were lower than in the premenopausal subjects . Mean serum FSH and LH levels decreased in all estradiol groups but not to the levels of the premenopausal subjects ; the greatest decrease occurred at the two highest estradiol doses . CONCLUSION A numerical dose-response relationship with hot flushes was seen in this pilot study comparing 0.05 , 0.1 , 0.2 , and 0.4 mg buccal estradiol . Only 0.4 mg 17-beta estradiol significantly reduced the occurrence of hot flushes compared to placebo ", "OBJECTIVE To investigate the effect of pulsed estrogen therapy S21400 ( intranasal 17 beta-estradiol ) on different quality of life ( QoL ) dimensions in early postmenopausal women treated with S21400 150 microg per day , S21400 300 microg per day , or placebo in a double blind , r and omized , controlled 2-year study . STUDY DESIGN QoL was assessed based on the vali date d Women 's Health Question naire design ed for peri- and post-menopausal women . Three hundred and thirty-five healthy , early postmenopausal Danish women , 53 years of age in average , who completed one question naire at baseline and one under study treatment were included in the analysis set . All analyses were performed on an intention-to-treat basis . RESULTS QoL improved significantly in both S21400 groups compared to placebo in the dimensions ' memory/concentration ' , ' vasomotor symptoms ' , ' sleep problems ' and ' sexual behavior ' ( difference in mean change scores being respectively + 7.9 , + 28.3 , + 9.9 and + 10.8 % , p ' anxiety/depressed mood ' and ' well-being ' . CONCLUSION Pulsed estradiol therapy had a pronounced effect not only on vasomotor symptoms but also a significant and clinical ly relevant improvement in several other QoL dimensions ", "CONTEXT Investigating the adverse effects of oral hormone replacement therapy ( HRT ) , the clinical effectiveness of alternative combinations and route of administrations . AIM To compare the effects of intranasal and transdermal 17 beta-estradiol combined with vaginal progesterone on vasomotor symptoms and vaginal cytology . SETTING S AND DESIGN A 12-week , prospect i ve , r and omized comparative study was conducted between July 2005 and September 2006 . MATERIAL S AND METHODS Eighty postmenopausal women aged between 42 - 57 years , who had scores of > or = 1.7 on the menopause rating scale-I ( MRS-I ) items \" 1 - 6 \" , were r and omly assigned to receive intranasal ( 300 microg/day , n = 40 ) or transdermal ( 50 microg/day , n = 40 ) 17 beta-estradiol continuously . All patients also received a vaginal progesterone gel twice weekly . Vasomotor symptoms were evaluated at weeks 0 , 4 , 8 and 12 . Vaginal maturation index ( VMI ) was evaluated at weeks 0 and 12 of the study . STATISTICAL ANALYSES The Mann-Whitney U and the Wilcoxon tests were used . P Thirty-two women in the intranasal and 29 women in the transdermal group completed the study . The total score of the MRS , the sum-scores of Factor 1 \" HOT FLUSHES \" and Factor 2 \" PSYCHE \" significantly decreased in both groups at week 4 . Factor 3 \" ATROPHY \" scores significantly decreased only in the transdermal group at week 12 . The VMI showed no changes within and between the two groups at the end of the study . CONCLUSION Intranasal and transdermal 17beta-estradiol combined with vaginal progesterone gel as a continuous HRT caused a similar decrease in vasomotor symptoms but did not have any significant effect on VMI after 12 weeks of treatment in this study population", "Progestogen treatment is associated with a number of subjective symptoms . In the present study , 148 healthy post-menopausal women suffering from mild climacteric symptoms were r and omly allocated to 12 weeks of treatment with ( a ) 2 mg oestradiol valerate combined with cyproterone acetate , medroxyprogesterone acetate or levonorgestrel ; ( b ) 1.5 mg 17 beta-oestradiol combined with desogestrel ; or ( c ) placebo . Climacteric symptoms , Kupperman index scores and potential adverse progestogen effects were recorded before treatment and three times per month during therapy . All the hormone regimens had a rapid effect , reducing the severity of climacteric symptoms to about 30 % of the baseline values ( P less than 0.001 ) within one month . Hot flushes were reduced in severity and /or frequency by 76 100 % within 3 months ( P less than 0.001 ) . The regimens which included hydroxyprogesterone derivatives produced a transient increase in breast tenderness . Other recorded potential adverse progestogen effects showed no significant changes during the study . We concluded that the addition of progestogens ( whether 19-nortestosterone or hydroxyprogesterone derivatives ) does not produce significant side effects during combined hormone replacement therapy", "Five women with premature ovarian failure were studied in a r and omized cross-over design to compare the biochemical effects of transdermal to oral estradiol administration when used in doses appropriate for endometrial preparation in a donor oocyte program . Patients r and omly received increasing dosages of oral micronized or transdermal estradiol for 4 week , with progesterone added in the last 2 weeks , to mimic a normal hormonal cycle . Serum sample s were assayed throughout treatment and compared to those from normally cycling premenopausal controls . In general , serum estradiol remained within the normal range in both treatment groups , whereas peak serum estrone levels were 10-fold higher in the orally treated group than those in the transdermally treated group . Serum levels of sex hormone-binding globulin , thyroid binding globulin , and renin substrate were all significantly elevated by day 14 in the orally treated patients and unchanged in the transdermal subjects . While plasminogen was unaltered by either route of administration , antithrombin-III levels fell with both treatments . Changes in gonadotropin levels were similar in both groups , with suppression of FSH by the end of the simulated cycles , but not into the normal premenopausal range . In conclusion , both estrogen replacement regimens provided near-normal serum estradiol profiles . However , despite the relatively high doses necessary to mimic a hormonally normal cycle , the transdermal route did not significantly alter the hepatic parameters studied , suggesting that this route of administration may have less adverse hepatic effects", "OBJECTIVE To develop a condition-specific quality of life question naire for the menopause with documented psychometric properties , based on women 's experience . METHODS SUBJECTS Women 2 - 7 years post-menopause with a uterus and not currently on hormone replacement therapy . Question naire development : A list of 106 menopause symptoms was reduced using the importance score method . Replies to the item-reduction question naire from 88 women result ed in a 30-item question naire with four domains , vasomotor , physical , psychosocial and sexual , and a global quality of life question . Psychometric properties : A separate sample of 20 women was used to determine face validity , and a panel of experts was used to confirm content validity . Reliability , responsiveness and construct validity were determined within the context of a r and omized controlled trial . Construct validation involved comparison with the Neugarten and Kraines'Somatic , Psychosomatic and Psychologic subscales , the reported intensity of hot flushes , the General Well-Being Schedule , Channon and Ballinger 's Vaginal Symptoms Score and Libido Index , and the Life Satisfaction Index . RESULTS The face validity score was 4.7 out of a possible 5 . Content validity was confirmed . Test-retest reliability measures , using intraclass correlation coefficients were 0.81 , 0.79 , 0.70 and 0.55 for the physical , psychosocial , sexual domains and the quality of life question . The intraclass correlation coefficient for the vasomotor domain was 0.37 but there is evidence of systematic change . Discriminative construct validity showed correlation coefficients of 0.69 for the physical domain , 0.66 and 0.40 for the vasomotor domain , 0.65 and -0.71 for the psychosocial domain , 0.48 and 0.38 for the sexual domain , and 0.57 for the quality of life question . Evaluative construct validity showed correlation coefficients of 0.60 for the physical domain , 0.28 for the vasomotor domain , 0.55 and -0.54 for the psychosocial domain , 0.54 and 0.32 for the sexual domain , and 0.12 for the quality of life question . Responsiveness scores ranged from 0.78 to 1.34 . CONCLUSIONS The MENQOL ( Menopause-Specific Quality of Life ) question naire is a self-administered instrument which functions well in differentiating between women according to their quality of life and in measuring changes in their quality of life", "The aim of this study was to evaluate the efficacy of pulsed estrogen therapy ( intranasal 17β-estradiol ) in the prevention of postmenopausal bone loss . A total of 386 women ( 40–65 years old ) , less than 5 years past menopause , were r and omized to intranasal placebo , 17β-estradiol 150 µg , or 300 µg daily for 2 years . Women with an intact uterus received micronised progesterone 200 mg per day , 14 days of each 28-day cycle . Women r and omised to placebo-treatment received placebo progesterone . The primary endpoints were changes in BMD at the spine ( L2–L4 ) and femoral neck . Secondary endpoints were changes in bone turnover markers : serum osteocalcin ( sOC ) as a marker of bone formation and urinary C-terminal telopeptides ( uCTX ) as a marker of bone resorption . BMD increased at all measured sites in women receiving active treatment in a dose-related manner , the difference compared to placebo being 5.2 % and 6.7 % at the spine , and 3.2 % and 4.7 % at the hip , respectively , with 150 μg and 300 μg ( P the spine and hip , respectively , was observed in women receiving placebo ( P risk factor for osteoporotic fracture , the difference between placebo and 150 μg or 300 µg was even higher at the spine ( 5.4 % and 7.4 % , respectively ) , and at the femoral neck ( 4.0 % and 5.2 % , respectively ) . Correspondingly , uCTX decreased from baseline by 39 % and 46 % , and sOC by 22 % and 27 % , in the 150 µg group and 300 µg group ( all P of bone turnover markers after 1 year and BMD after 2 years , emphasizing that bone markers can predict BMD response during hormonal treatment . Acceptability and general tolerance were good . This study demonstrates that pulsed estrogen therapy at the dose of 150 μg and 300-μg per day prevents bone loss in a dose-dependant manner at each site studied , and normalizes bone turnover markers to premenopausal levels", "OBJECTIVE : To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol ( E2 ) gel for relief of menopausal symptoms in a population of postmenopausal women . METHODS : This study was a r and omized , double-blind , placebo-controlled , multicenter , parallel-group study . Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d ( n=136 ) , 1.7 g/d ( n=142 ) , or 2.6 g/d ( n=69 ) E2 gel or placebo gel ( n=137 ) topically for 12 weeks . The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined . RESULTS : With increasing E2 doses , mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3–5 , E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day ( P in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group . At week 12 , vaginal pH was more acidic and vaginal maturation index more mature compared with placebo ( P most bothersome vulvovaginal atrophy symptoms ( P well tolerated at the site of application and produced no unexpected adverse effects . The 0.87 g/d dose produced fewest adverse events . CONCLUSION : The 0.87 g/d dose of this new transdermal E2 gel , which delivers an estimated 0.0125 mg E2 daily , delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00391417 LEVEL OF EVIDENCE :", "Objective The aim of this study was to determine the efficacy , safety , and lowest practical dose of a transdermal estradiol gel in the treatment of symptomatic postmenopausal women . Methods Healthy postmenopausal women with seven or more moderate to severe hot flushes per day or 50 to 60 or more per week were r and omized to transdermal gel containing 1.5 mg ( n = 73 ) or 0.75 mg ( n = 75 ) estradiol ( EstroGel 0.06 % ) or placebo ( n = 73 ) in a phase 3 study , or to 0.375 mg ( n = 119 ) or 0.27 mg ( n = 118 ) estradiol ( 0.03 % gel ) or placebo ( n = 114 ) in a phase 4 study . Results The frequency of moderate to severe hot flushes and severity of all hot flushes significantly decreased versus placebo at weeks 4 and 12 with 1.5 , 0.75 , and 0.375 mg estradiol . Overall participant responder rates were generally lower in the phase 4 study than those in the phase 3 study with the approved 0.75-mg estradiol dose . Vaginal maturation index ( VMI ) shifts from baseline to week 12 were significant ( P estradiol versus placebo ; VMI improved ( P superficial cells increased ( P = 0.005 ) , and parabasal cells decreased ( P = 0.002 ) with 0.375 mg estradiol vs placebo but not with 0.27 mg estradiol . The most frequently reported treatment-emergent adverse events , although not necessarily treatment related , were headache , infection , breast pain , and nausea ( phase 3 study ) and insomnia and headache ( phase 4 study ) . No serious adverse events were related to treatment ; no deaths occurred . Conclusion A transdermal gel with 0.75 mg estradiol was the lowest practical dose that effectively reduced the frequency and severity of moderate to severe hot flushes , improved VMI , and was well tolerated", "ABSTRACT Objectives To determine the efficacy and safety of low-dose maintenance therapy with transdermal estradiol ( E2 ) gel in Japanese women with climacteric disorder and estrogen deficiency symptoms . Methods Women ( n = 209 ) aged 37–59 years who had climacteric disorder or estrogen deficiency symptoms received a st and ard dose of transdermal E2 gel ( 1.8 g/day , containing E2 1.08 mg/day ) for 8 weeks as induction treatment . A total of 177 women in whom the number of daily hot flushes had decreased to less than one-third of the baseline value ( marked improvement ) at week 8 were double-blindly r and omized to receive low-dose E2 ( n = 88 , 0.9 g/day , containing E2 0.54 mg/day ) or E2-free placebo ( n = 89 ) for 16 weeks . Results Improvement rates in the number of daily hot flushes at the final evaluation ( primary endpoint ) in the low-dose E2 group ( marked 90.8 % , moderate 6.9 % , mild 1.1 % , no change 1.1 % , worsening 0 % ) were significantly greater than in the placebo group ( marked 77.0 % , moderate 10.3 % , mild 4.6 % , no change 2.3 % , worsening 5.7 % ) ( p = 0.0097 ) , showing an inhibitive effect on the flare-up of climacteric symptoms . The incidence of treatment-related adverse events in the low-dose group ( 21.6 % ) was similar to that in the placebo ( 22.5 % ) but was lower than that in the st and ard-dose treatment ( 32.5 % ) . Conclusions Low-dose maintenance therapy that was half the st and ard dose of transdermal E2 gel ( 0.9 g/day ) applied to women who had achieved marked improvement in the number of hot flushes at the st and ard dose ( 1.8 g/day ) was demonstrated to be effective ( inhibition of recurrence ) and safe for the treatment of climacteric disorder and estrogen deficiency symptoms", "OBJECTIVE The efficacy and safety of chlormadinone acetate ( CA ) versus micronized progesterone ( P ) were assessed in non-hysterectomized postmenopausal women . MATERIAL S AND METHODS This was a multicenter , r and omized , parallel group study with a 6-month double-blind period followed by a 12-month open period . Patients were r and omized to receive every month during 18 months percutaneous 17 beta-estradiol ( E(2 ) ) 1.5 mg/day from Day 1 to 24 of treatment cycle , combined from Day 11 to 24 to either CA 10 mg/day ( n=167 ) or P 200 mg/day ( n=169 ) . Endometrial biopsy ( EB , main analysis criterion ) was performed at baseline , and at Day 18 - 24 of the 6th and 18th cycles . RESULTS At Month 6 , EB did not evidence any hyperplasia . EB were inadequate for assessment in 24.5 % and 47.5 % of patients in the CA and MP groups , respectively . CA was found to be as protective as P ( 96.3 % and 92.0 % of success ) . However , the hormonal status of the endometrium differed ( P secretory endometrium was found in 81.5 % of the CA patients , compared to 50.7 % in the P group . These transformations result ed in predictable , cyclic bleeding in 94.5 % of the CA patients , compared to only 62.3 % of the P patients ( P=0.0001 ) . Unscheduled bleeding , spotting and /or metrorrhagia , were more frequent under P than under CA ( 17.9 % and 13.7 % , respectively ) . The beneficial effects on hot flushes were more important in the CA group than in the P ( P clinical results were similar to those obtained at Month 6 . The safety profile , particularly the lipid one , was similar in both groups , except for drowsiness and dizziness , which were significantly more frequent under P than under CA . CONCLUSION The progestative effects of CA on the endometrium and on menopause-related symptoms were at least as good as those of P. Moreover , CA result ed more often than P in secretory effects , and in satisfying bleeding patterns", "OBJECTIVE To compare the effectiveness of tibolone and 17beta-estradiol on climacteric symptoms , in a r and omized , single-blind , cross-over study in surgically menopausal women . MATERIAL AND METHODS Forty surgically menopausal women were divided r and omly into two groups . Group A received treatment with tibolone for 6 months , while group B received 17beta-estradiol . After 3 weeks washout period , treatment protocol s were exchanged for another 6 months . The climacteric symptoms were assessed with Greene Climacteric Scale at baseline , during washout and after the treatments . Statistical analysis was done with the Wilcoxon 's Sign Rank test . RESULTS Both treatments significantly improved the scores of all subscales with respect to baseline . However , the improvement in psychological , somatic and sexual subscales were significantly superior in the tibolone group compared with 17beta-estradiol group . Both treatments showed comparable improvements in the relief of vasomotor symptoms . CONCLUSION Our findings suggest that tibolone may improve mood , libido and somatic symptoms in surgically menopausal women to a greater extent than estrogen therapy alone", "OBJECTIVE To compare the efficacy of two strengths of an estradiol matrix transdermal delivery system with daily oral doses of conjugated equine estrogens in reducing the frequency of moderate-to-severe hot flushes in postmenopausal women . DESIGN The design of the study provided for the following treatment regimens : an estradiol transdermal delivery system ( Alora 0.05 or 0.1 mg/day ) administered twice weekly or oral doses of conjugated equine estrogens ( CEE 0.625 or 1.25 mg ) administered daily were given to 321 highly symptomatic postmenopausal women for 12 weeks following a r and omized , parallel-group , double-blind , double-dummy design . RESULTS Results indicate no statistically significant differences at any time point in mean frequency or mean percentage reduction in frequency of moderate-to-severe hot flushes between patients given Alora 0.1 mg/day and those receiving CEE 1.25 mg/day . Similarly , no significant differences were observed at any time in mean frequency of moderate-to-severe hot flushes between the Alora 0.05 mg/day and CEE 0.625 mg/day groups , although the group receiving CEE 0.625 mg/day exhibited a statistically greater percentage reduction than the Alora 0.05 mg/day group at weeks 3 , 4 and 8 . By week 12 , these two treatments were statistically indistinguishable . There were no serious or unexpected adverse events with the two transdermal systems and local skin tolerability was excellent . Other estrogenic effects such as restoration of vaginal cytology , breast tenderness and unexpected vaginal bleeding were comparable between transdermal and oral administration groups except for a lower incidence of bleeding in those women receiving the lower dose transdermal regimen", "OBJECTIVE To evaluate the efficacy and safety of a new , seven-day , transdermal estradiol system in healthy postmenopausal women with hot flushes . METHODS Two studies are described . In the first study , subjects were r and omized to treatment with a 0.05 mg/day estradiol patch , a 0.1 mg/day estradiol patch , or a placebo patch ; and in the second study , to treatment with either of the two estradiol patches or oral conjugated estrogens ( as Premarin ) 0.625 mg/day . Efficacy was evaluated on the basis of diary entries recording hot-flush frequency and severity . Subjects ' and investigators ' global assessment s of treatment efficacy were recorded at follow-up visits . RESULTS In Study 1 , both the 0.05-mg and 0.1-mg estradiol patches were significantly more effective than placebo in reducing hot flushes and were associated with higher global assessment s. In Study 2 , all three active treatments produced a significant reduction in the number of hot flushes compared with base-line . There were no statistically significant between-group differences , although the response to the 0.1-mg estradiol patch was greater , and to the 0.05-mg estradiol patch less , than the response to conjugated estrogens . The patches were generally well tolerated . Skin irritation from the patch was the most common adverse experience in both studies . CONCLUSIONS The new , seven-day , transdermal system effectively and safely treats post-menopausal vasomotor symptoms", "Objective The use of estrogen and progesterone to manage vasomotor symptoms ( ie , hot flashes and night sweats ) has declined because of concerns about their risks , and there is an increased interest in alternate , effective , and low-risk treatments . This study reports the results of a r and omized controlled trial of clinical hypnosis for treating vasomotor symptoms among postmenopausal women . Methods This is a r and omized , single-blind , controlled , clinical trial involving 187 postmenopausal women reporting a minimum of seven hot flashes per day ( or at least 50 hot flashes a week ) at baseline between December 2008 and April 2012 . Eligible participants received five weekly sessions of either clinical hypnosis or structured-attention control . Primary outcomes were hot flash frequency ( subjectively and physiologically recorded ) and hot flash score assessed by daily diaries on weeks 2 to 6 and week 12 . Secondary outcomes included measures of hot flash – related daily interference , sleep quality , and treatment satisfaction . Results In a modified intent-to-treat analysis that included all r and omized participants who provided data , reported subjective hot flash frequency from baseline to week 12 showed a mean reduction of 55.82 ( 74.16 % ) hot flashes for the clinical hypnosis intervention versus a mean reduction of 12.89 ( 17.13 % ) hot flashes for controls ( P mean reduction in hot flash score was 18.83 ( 80.32 % ) for the clinical hypnosis intervention as compared with 3.53 ( 15.38 % ) for controls ( P mean reduction in physiologically monitored hot flashes was 5.92 ( 56.86 % ) for clinical hypnosis and 0.88 ( 9.94 % ) for controls ( P hot flash – related interference ( P sleep quality ( P treatment satisfaction ( P hot flashes and hot flash scores in postmenopausal women", "Objective : To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years . Design : This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial , a r and omized , placebo-controlled , double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol . Four hundred seventeen postmenopausal women , aged 60 to 80 years , were r and omly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d ( n = 208 ) or placebo ( n = 209 ) . Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a st and ardized question naire . Results : At baseline , 16 % of women reported hot flashes , 32 % reported vaginal dryness , and 35 % reported trouble sleeping . Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes , vaginal dryness , or sleep difficulties than those who received placebo . Treatment with ultralow-dose estradiol did not cause breast tenderness , uterine bleeding , or other symptoms often attributed to estrogen , but vaginal discharge was more common in women who received estradiol compared with those who received placebo . Conclusion : In this population of older , largely asymptomatic women , ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge . Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger , more symptomatic women", "Several formulations combining estrogens and progestins for hormone therapy ( HT ) have been approved worldwide for the treatment of menopausal symptoms , yet recent data indicate a decline in their use and an increase in compounded bioidentical HT . Up to now , no single product combining natural 17β-estradiol and progesterone has been approved by the US Food and Drug Administration ( FDA ) or the European Medicines Agency ( EMA ) . A phase 3 trial ( REPLENISH ) is underway to study a novel oral formulation of solubilized 17β-estradiol and natural progesterone combined in a single gelatin capsule ( TX-001HR ; TherapeuticsMD , Inc , Boca Raton , FL ) for treating vasomotor symptoms ( VMS ) in postmenopausal women . The REPLENISH trial evaluates the efficacy and safety of TX-001HR ( 4 doses ) versus placebo for the reduction of moderate to severe VMS frequency and severity at 4 and 12 weeks and evaluates the endometrial safety of the combinations at 1 year . TX-001HR contains hormones that are molecularly identical to endogenous estradiol and progesterone and is intended as an option for women who prefer bioidentical hormones ; further , it does not contain peanut oil , a common allergen . The constituents of TX-001HR , in a pharmacokinetic report , showed similar bioavailability and safety compared with reference estradiol tablets and micronized progesterone capsules administered together . Published data suggest a safer profile of estradiol and natural progesterone compared with HT containing conjugated equine estrogens and progestins . This report summarizes the methodology of the REPLENISH trial and review s the evidence suggesting clinical differences between HT containing progesterone or progestins , and estradiol or conjugated equine estrogens", "Objective To compare the efficacy and patient acceptability of intranasal versus transdermal 17β-estradiol ( E2 ) delivery systems for postmenopausal symptoms . Methods Postmenopausal women were r and omly assigned to intranasal 17β-E2 , 300 μg daily ( n = 176 ) or transdermal 17β-E2 ( delivering 50 μg/day ) , two patches per week ( n = 185 ) for 12 weeks , followed by a 4-week period with the alternate treatment . Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12 . Patient acceptability was compared by patient choice of administration route and by question naire at week 16 . Results Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12 . Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups ( P the Kupperman Index score of −0.5 ± 0.9 ( 95 % confidence interval −2.3 , 1.3 ) was within the predetermined interval of equivalence . Both therapies were well tolerated with similar adverse event rates , except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 ( 7.2 % ) than with the patch ( 15.5 % , P = .02 ) . Sixty-six percent of patients chose to continue the intranasal therapy and 34 % the transdermal therapy ( P Satisfaction was greater with intranasal therapy at week 16 ( P Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles . Intranasal therapy was the patients ' choice for long-term treatment", "Objective : To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone ( T ) , thyroxine ( T4 ) , and cortisol ( C ) and the concentrations of their serum binding globulins sex hormone-binding globulin , thyroxine-binding globulin , and cortisol-binding globulin in naturally menopausal women . Design : R and omized , open-label , crossover . Interventions included a 6-week withdrawal from previous hormone therapy ( baseline ) , followed in r and omized order by 12 weeks of oral conjugated equine estrogens ( CEE ) ( 0.625 mg/d ) and 12 weeks of transdermal estradiol ( TD E2 ) ( 0.05 mg/d ) , with oral micronized progesterone ( 100 mg/d ) given continuously during both transdermal estrogen therapy regimens . Results : Twenty-seven women were enrolled in the study , and 25 completed both treatment periods . The mean(SD ) percentage changes from baseline of sex hormone-binding globulin , total T , and free T with oral CEE were + 132.1 % ( 74.5 % ) , + 16.4 % ( 43.8 % ) , and −32.7 % ( 25.9 % ) , respectively , versus + 12.0 % ( 25.1 % ) , + 1.2 % ( 43.7 % ) , and + 1.0 % ( 45.0 % ) with TD E2 . The mean ( SD ) percentage changes of thyroxine-binding globulin , total T4 , and free T4 with oral CEE were + 39.9 % ( 20.1 % ) , + 28.4 % ( 29.2 % ) , and −10.4 % ( 22.3 % ) , respectively , versus + 0.4 % ( 11.1 % ) , −0.7 % ( 16.5 % ) , and + 0.2 % ( 26.6 % ) with TD E2 . The mean ( SD ) percentage changes of cortisol-binding globulin , total C , and free C with oral CEE were + 18.0 % ( 19.5 % ) , + 29.2 % ( 46.3 % ) , and + 50.4 % ( 126.5 % ) , respectively , versus −2.2 % ( 11.3 % ) , −6.7 % ( 30.8 % ) , and + 1.8 % ( 77.1 % ) with TD E2 . Concentrations of all hormones and binding globulins were significantly different ( P ≤ 0.003 ) during administration of oral versus transdermal estrogen therapy , except for free T4 and free C. Conclusions : Compared with oral CEE , TD E2 exerts minimal effects on the total and free concentrations of T , T4 , and C and their binding proteins", "The treatment of postmenopausal symptoms was studied in 26 healthy women using a new synthetic rubber ( Kraton D 2109 ) vaginal ring containing 53 mg of 17 beta-oestradiol . All women were postmenopausal , at least 6 months after the last vaginal bleeding and suffering from daily hot flushes . The study was conducted in a double-blind placebo-controlled intrapatient cross-over fashion , and the study period was 6 months . The rings used give an initial in vitro release rate of 0.4 mg/E2 per day . The in vitro release rate decreases to about 0.2 mg/day after 20 days and levels off asymptotically to about 0.1 mg/day after 50 days . Serum E2 levels equivalent to the follicular phase of the normal menstrual cycle were measured after 1 month 's use , and serum E2 level stayed above postmenopausal levels throughout the study period . FSH was suppressed during use of the E2-releasing vaginal ring , while LH showed no statistically significant suppression in continued use . Postmenopausal complaints were recorded by Visual Analogue Scales ( VAS ) as judged by both the patient and the examining doctor ; all complaints had favourable outcomes during use of the E2-releasing vaginal ring without deterioration of symptoms during use of the placebo ring . No serious side-effects were encountered , and the possibility of managing all postmenopausal complaints with intravaginal oestrogen treatment is discussed", "Objective To determine the efficacy and local tolerance of a new matrix transdermal drug-delivery system that delivers 0.02 mg of 17β-estradiol ( E2 ) daily for 7 days for the relief of vasomotor symptoms . Methods A total of 324 surgically or naturally menopausal women , all with prior hysterectomy and moderate to severe vasomotor symptoms ( 56 - 140 hot flushes per week , with episodes of sweating , during a baseline observation period ) , participated in two independent , 12-week , r and omized , double-blind , placebo-controlled studies . After a 4-week , treatment-free period , each woman received a continuous regimen of either one E2 transdermal system , two E2 transdermal systems , or placebo transdermal system(s ) applied every week for 12 weeks . Efficacy was measured as reduction in hot flush frequency , determined from subject diaries . To measure local tolerance , skin irritation ( erythema and edema ) was objective ly and systematic ally evaluated under blue light after removal of the transdermal system(s ) . Serum E2 and estrone concentrations were determined in one of the studies during baseline and on days 1 , 9 , 30 , 58 , 79 , and 84 . Results Mean hot flush frequency decreased from 80 hot flushes per week at baseline to approximately 13 hot flushes per week ( 84 % decrease ) after 12 weeks of transdermal E2 treatment . Compared with placebo , the decrease in hot flush frequency was significant as early as weeks 2 and 3 , and was maintained through the end of the study . Few clinical ly significant skin reactions occurred , and only nine ( 3 % ) of the subjects withdrew because of a skin effect . After initial increase , serum E2 concentrations remained stable throughout the study , achieving values of approximately 20 and 40 pg/mL above baseline for one and two E2 transdermal systems , respectively . Conclusion The E2 transdermal system effectively reduced the frequency of moderate to severe vasomotor symptoms as early as the second week of therpy and was very well tolerated . The decrease in hot flush frequency was similar to that reported for oral and other transdermal estrogens , but at lower serum E2 concentrations . This result may be due to the stable E2 blood level achieved with this transdermal system", "Background and Objective The highest level of scientific evidence available for each therapy for menopausal symptoms was sought , for example , systematic review s of r and omised controlled trials ( RCTs ) . Results There is reasonable evidence that some symptoms are modified by lifestyle , for example , cessation of smoking , exercise , reduction of alcohol , diet and alleviation of psychosocial stress . No complementary medicine , for example , phytoestrogens , black cohosh , herbal or homeopathic medicines or complementary therapies , for example , acupuncture , yoga , chiropractic manipulation , reflexology or magnetic devices have a greater effect than the usual placebo effect seen in quality blinded RCTs . Some have potential side-effects . So-called ' bioidentical hormones ' have no evidence -base and potential for harm . None of the above therapies have evidence of efficacy and long-term safety . Selective serotonin and noradrenaline re-uptake inhibitors ameliorate vasomotor symptoms and sometimes menopausal depression better than placebo . The most effective therapy for menopausal ( oestrogen ) deficiency symptoms is oestrogen which is the main component of hormone replacement therapies ( HRT ) . Compared with placebo HRT is highly effective in relieving hot flushes , night sweats , dry vagina and dyspareunia . It also improved joint pains , sexuality and sleeplessness and reduced subsequent fractures in RCTs . The increased risk of oral HRT for thromboembolism is small around menopause , for those without thrombotic risk factors , and is not elevated with non-oral routes . Cardiovascular disease may be reduced when HRT is initiated near menopause . Breast cancer risk increases after several years with the use of oral HRT containing progestogens at an annual rate of 8/10 000 ( breast cancer risk was seen with oestrogen-only HRT", "Regularly menstruating women are relatively protected from cardiovascular disease . Epidemiological and endothelial function studies attribute this protection to estradiol ( E(2 ) ) , but both progesterone ( P ) and E(2 ) are normally present . A range of vascular effects of added progestins have been described , from neutral to detrimental , but the effects of P per se on endothelial function in humans have not been reported . We therefore investigated the acute effects of E(2 ) , P , and E(2 ) combined with P , on endothelium-dependent and -independent forearm blood flow responses . Using venous occlusion plethysmography , forearm blood flow ( FBF ) was measured during acute brachial artery infusions , achieving physiologic levels of 17-beta-E(2 ) , P , and 17-beta-E(2 ) with P in healthy menopausal women with no cardiovascular disease risk factors . Vehicle or hormones were infused , in r and om order , on 4 days , 1 week apart . Flow responses were measured during coinfusions of hormone with the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside . Twenty-seven healthy menopausal women were studied , and all had normal baseline endothelial responses . Small ( approximately 15 % ) , statistically nonsignificant increases in endothelium-dependent flow responses were seen after all acute hormone treatments . No impairment in response was seen with P alone or in combination with 17-beta-E(2 ) . In healthy menopausal women without cardiovascular disease risk factors and without baseline defects in endothelial function , acute exposure to physiologic levels of 17-beta-E(2 ) , P , and 17-beta-E(2 ) with P produced equivalent endothelium-dependent responses . These data suggest that P does not have detrimental vascular effects in humans", "Objective : To assess the efficacy and safety of topical micellar nanoparticle estradiol emulsion ( MNPEE ; Estrasorb ; Novavax , Inc. , Malvern , PA ) in postmenopausal women with moderate to severe vasomotor symptoms . Design : A multicenter , r and omized , double-blind , placebo-controlled study was conducted in 200 postmenopausal women with seven or more moderate to severe hot flushes per day . The study consisted of a 3-week screening period followed by a 1-week placebo emulsion run-in period and a 12-week active or placebo treatment period . Women were r and omized ( 1:1 ) to receive MNPEE ( 3.45 g daily dose of emulsion containing 8.6 mg estradiol ) or matching placebo emulsion . The primary efficacy variable was the change from baseline in the frequency of moderate and severe hot flushes at weeks 4 and 12 . Adverse events were monitored throughout the trial . Results : Topical micellar nanoparticle estradiol emulsion was statistically significantly superior to placebo emulsion in reducing the mean frequency of moderate to severe vasomotor symptoms by week 3 ( P = 0.003 ) , with superiority to placebo maintained from weeks 4 to 12 ( P mean daily frequency of hot flush count by 11.1 ( P mean symptom severity from weeks 4 to 12 ( P mean serum concentrations of estradiol and estrone were 63 and 89 pg/mL , respectively , in the MNPEE group . The mean endpoint ratio of estradiol to estrone in these patients was 0.774 . MNPEE was safe and well tolerated . Conclusion : Once-daily application of 3.45 g of micellar nanoparticle estradiol emulsion containing 8.6 mg of estradiol was safe and effective in providing significant relief of vasomotor symptom frequency and severity in postmenopausal women", "OBJECTIVE Bioidentical compounded hormone therapy is popular among patients , but providers do not have pharmacokinetic information or dosing guidelines for these preparations . Our objective was to compare the pharmacokinetics of the commonly used compounded preparations with conventional hormonal preparations that are considered bioequivalent in practice . METHODS We conducted a r and omized , blinded , four-arm 16-day clinical trial of forty postmenopausal women assigned to one of three doses of a compounded estrogen cream ( Bi-est ( 80:20 ) ; 2.0 , 2.5 , or 3.0 mg)+compounded oral progesterone 100 mg , or to a conventional estradiol patch ( Vivelle-Dot ™ 0.05 mg)+Prometrium ™ 100 mg . Serum levels of estrone , estradiol , estriol , and progesterone were obtained at multiple time intervals during the first 24-h , and at steady-state . RESULTS Results were analyzable for 37/40 women . Study medications were well tolerated . The AUC at 24h and at steady-state for estrogens remained consistently lower for all doses of Bi-est tested relative to the patch . The difference was statistically significant for Bi-est 2.0 mg ( AUC-estradiol=181 vs. 956 ; p vs. 917 ; p remained low in all study arms . Serum progesterone levels were comparable in conventional vs. compounded groups . CONCLUSIONS This pharmacokinetic trial showed that the currently used doses of compounded hormones yield lower levels of estrogen compared to the st and ard-dose estradiol patch . To find comparable doses , further studies are needed . This successfully conducted r and omized controlled study attests to the feasibility of using a similar design in the setting of a larger clinical trial", "BACKGROUND Relief of climacteric symptoms is currently the main role of hormone therapy . However , vaginal bleeding complicating this therapy is among the leading causes for its early discontinuation . OBJECTIVES To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms , produce an acceptable pattern of vaginal bleeding and control endometrial proliferation . METHODS Twenty-nine postmenopausal women with an intact uterus were studied . All had climacteric symptoms . The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone ( high dose progesterone ) or 1.8 g ( low dose progesterone ) , and were kept in place for 4 - 6 months . Serum progesterone , estradiol and estrone were measured and endometrial thickness determined . All women kept a daily diary of bleeding/spotting and completed a question naire on climacteric symptoms at monthly intervals . The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women . RESULTS A total of 18 patients ( 9 in each group ) completed the study . Mean levels of estradiol , estrone and progesterone were at their peak after 2 to 4 weeks . All rings were effective in alleviating vasomotor symptoms , although there was evidence of \" escape from effect \" in month 6 . Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia . Of the 18 women who completed the study , 5 had amenorrhea throughout , 7 had amenorrhea after 3 months , and the remainder had one or two bleeding episodes after 3 months . Therapy was discontinued in 11 women . CONCLUSIONS A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms , prevented endometrial proliferation , and provided an acceptable bleeding pattern . It should be viewed as a possible alternative for short-term estrogen-progesterone therapy", "OBJECTIVE The main purpose in organizing this survey was to collect information relevant to The North American Menopause Society 's ( NAMS ) educational mission and to document women 's knowledge of , and attitudes toward , menopause . DESIGN During June-July 1997 , The Gallup Organization conducted 750 telephone interviews with a r and omly selected sample of women 45 - 60 years of age from across the United States . Women were asked about their sources of information on menopause , what changes in health they anticipated as a result of menopause , why they used hormone therapy , and their attitudes toward menopause as a natural or a medical event . RESULTS Women are more likely to believe that depression and irritability are associated with menopause than heart disease , but only a few associate menopause with an increasing vulnerability to either memory loss or Alzheimer 's disease . Relief of physical symptoms of menopause was mentioned as the reason for starting hormone therapy more often than to protect against osteoporosis ( 25 % relative to 15 % ) , or to prevent stroke or a heart attack ( 10 % ) , or to reduce the risk of developing Alzheimer 's disease ( 2 % ) . The single main source of women 's information on menopause was a health professional ( 49 % ) . The majority of women who were already menopausal or experiencing menstrual changes expressed an attitude toward menopause that was either neutral ( 42 % ) or positive ( 36 % ) . CONCLUSIONS Women are divided in their views of menopause , some seeing it as a medical condition requiring medical treatment , whereas others see it as a natural transition to be managed by \" natural \" means . Providing women with accurate , up-to- date information and enhancing communication between healthcare providers and menopausal women remain the challenges for NAMS", "BACKGROUND Because natural progesterone is poorly absorbed and rapidly metabolized , synthetic derivatives of progesterone , such as medroxyprogesterone acetate ( MPA ) , are used in combination with estrogen in hormone replacement therapy . A micronized form of natural progesterone is available that is readily absorbed and reaches peak serum concentrations from 1 to 4 hours after administration . OBJECTIVE The purpose of this study was to compare the quality of life ( QOL ) , menopausal symptoms , and costs associated with a natural micronized progesterone ( MP ) formulation versus MPA as add-on therapy to estrogen in hormone replacement for post-menopausal women . METHODS This prospect i ve , multicenter , r and omized , fixed-dose , open-label , parallel-group study enrolled postmenopausal , otherwise healthy , nonhysterectomized women 45 to 65 years of age who had been amenorrheic for > or = 6 months and exhibited symptoms of estrogen deficiency . All women received 0.625 mg conjugated equine estrogens on days 1 to 25 of a 30-day cycle ; on days 12 to 25 , women were r and omized to receive either MP 200 mg or MPA 5 mg ; patients were followed for 9 months . QOL , the primary end point , was measured at baseline and months 3 , 6 , and 9 using the 36-Item Short-Form Health Survey ( SF-36 ) , the Nottingham Health Profile ( NHP ) , and the condition-specific Women 's Health Question naire ( WHQ ) . Bleeding pattern , compliance , menopausal symptoms , and cost were evaluated as secondary end points . Costs ( in 1997 Canadian dollars ) were assessed from the societal perspective and included costs of study medication , hormone therapy monitoring , concomitant medication , outpatient re sources , out-of-pocket expenses , and patient and caregiver time loss . RESULTS A total of 182 women were enrolled ; 89 received MP and 93 received MPA . Improvements in climacteric symptoms were observed from baseline to month 9 for both treatments . Mean scores on all domains of the SF-36 at month 9 were greater than scores at baseline in both treatment groups but the increases were not statistically significant . All domains within the NHP and WHQ improved significantly over this period for both groups ( P menstrual problems and cognitive domains of the WHQ . The difference in average 9-month cost per patient was not statistically significant , at Can 367 dollars + /- 120 dollars and Can 360 dollars + /- 369 dollars for patients receiving MP and MPA , respectively . CONCLUSIONS MP is a clinical ly effective , well-tolerated , and cost-comparable alternative to MPA", "OBJECTIVES To compare continuous and cyclical transdermal estrogen replacement therapy ( ERT ) with or without an oral progestogen regarding climacteric symptoms , body weight and bleeding pattern . METHODS A total of 2459 postmenopausal women were treated for three cycles of 28 days in an open , r and omized , parallel group multicenter study . Patients received an estrogen matrix patch ( 50 micrograms 17/beta-estradiol/day ) twice weekly , either continuously ( eight patches/cycle ) or cyclically ( six patches/cycle , i.e. 3 weeks on , 1 week off ) . A total of 1232 patients were treated continuously and 1227 cyclically . In the study group 1150 patients had an intact uterus ( 543 in the continuous and 607 in the cyclical treatment arm ) and received , in addition to the estrogen patch , an oral progestogen in a transformation dose for 12 days of each cycle . Hysterectomized patients totaling 1309 ( 689 in the continuous versus 620 in the cyclical group ) did not receive progestogen . Of the 2459 patients , 771 ( 31.4 % ) participated in a follow-up study with two further treatment cycles , which was offered to the patients at the end of the main study . The main outcome measures were climacteric symptoms , measured at the end of cycles 1 - 3 by a Visual Analogue Scale at baseline , and body weight measured at baseline at the end of cycles 3 and 5 . In addition , the bleeding time per cycle ( days ) was evaluated in all patients with an intact uterus . RESULTS Continuous and cyclical transdermal ERT reduced , over three treatment cycles , the average climacteric symptom score by 1.77 and 1.70 , respectively . The percentage remission and improvement rates for the ten climacteric symptoms ranged between 69.3 and 88.0 % and did not differ between the two groups . In patients with a higher symptom score at baseline , the continuous treatment was slightly more effective . However , this effect was statistically not significant . After three treatment cycles body weight increased in both treatment groups by between 500 and 700 g. Further treatment during the follow-up study induced an additional average weight gain of 200 - 400 g. These results were not influenced by the addition of an oral progestogen . In patients with an intact uterus , the average bleeding time at the end of the first cycle ( 5.4 days in the continuous versus 5.3 days in the cyclical group ) increased slightly during cycle 2 and returned to baseline values at the end of cycle 3 . CONCLUSIONS Continuous and cyclical transdermal ERT were equally effective in reducing climacteric symptoms . The short term use of five cycles transdermal ERT induced a slight increase in body weight which was independent of the treatment regimen . These results were not influenced by the type and mode of administration of a progestogen . Both ERT regimens were very well tolerated and are suitable alternatives for estrogen replacement therapy of postmenopausal women", "One hundred and ten ( 110 ) healthy early post-menopausal women with mild subjective vasomotor symptoms ( mean Kupperman index score 11 ) participated in a long-term , double-blind , placebo-controlled therapeutic trial . The effects of 2 hormone regimens were evaluated . Group I received percutaneous oestrogen therapy for 2 yr , opposed by oral micronized progesterone ( 200 mg ) during the second year , while Group II received oral 17 beta-oestradiol valerate together with cyproterone acetate ( CPA ) . The serum oestrogen concentrations differed markedly in the 2 treatment groups . In Group I the serum/oestrone/oestradiol ratio was 1 ( comparable to the pre-menopausal value ) , but in group II the ratio was greater than 5 . Despite the difference in the serum oestradiol and oestrone concentrations , the mean symptom scores were rapidly and similarly reduced in both treatment groups ( P less than 0.001 ) . They remained low throughout the study and were not significantly different from pre-menopausal values", "OBJECTIVE To evaluate the bleeding patterns and clinical compliance associated with postmenopausal amenorrhea-inducing forms of hormone replacement therapy using either percutaneous estradiol-gel and a levonorgestrel-releasing intrauterine device or an oral/vaginal natural progesterone . METHODS Sixty postmenopausal women with an intact uterus were followed over 12 months in this open , non-r and omised , parallel group study . All patients continuously received a gel containing 1.5 mg of estradiol daily . The women were divided into three groups on the basis of progestin administration . Twenty women ( group I ) had a levonorgestrel-releasing device ( LNG-IUD ) inserted at the beginning of the study . Twenty-one women ( group II ) received oral natural micronised progesterone ( oral P ) 100 mg daily during 25 calendar days each month , and 19 women ( group III ) used vaginal natural micronised progesterone ( vaginal P ) 100 - 200 mg daily during 25 calendar days each month ( higher dose if spotting occurred ) . Clinic visits were at 0 , 3 , 6 and 12 months . Bleeding patterns were recorded by the patient in a diary and clinical compliance was evaluated at control visits during the treatment . Symptoms were recorded using a modified Kuppermann index . The serum estradiol concentration was determined at the 0 , 6 and 12 month control visits . RESULTS 80 % ( n = 16 ) of the patients in the LNG-IUD group , 67 % ( n = 14 ) in the oral P group II and 53 % ( n = 10 ) in the vaginal P group were without bleeding at 12 months . Spotting was common during the first 3 months . Symptom relief was good in each group . The LNG-IUD did not cause any serious side-effects . Compliance was good for LNG-IUD and oral progesterone but not for vaginal progesterone . CONCLUSIONS Percutaneous estradiol-gel associated with LNG-IUD is an appropriate method of hormone replacement therapy . The combination of oral natural progesterone with estradiol-gel is also useful , although bleeding episodes complicated the treatment in one third of the patients . The vaginal administration of natural progesterone was impractical due to bleeding disorders", "OBJECTIVE To establish whether estrogen treatment affects well-being in postmenopausal women without current or previous vasomotor symptoms . DESIGN Forty postmenopausal women , aged 45 - 59 years , without current or previous vasomotor complaints , were included . They were r and omized to masked treatment with either transdermal 17beta-estradiol 50 microg/24 h or to placebo . At baseline and after 12 and 14 weeks of treatment , the women completed a question naire which reflects well-being , the Psychological General Well-Being ( PGWB ) Index . RESULTS The women scored high on the PGWB Index , both at baseline and after 12 and 14 weeks of treatment . There was no significant difference in well-being according to PGWB Index between the groups treated with estrogen and placebo , neither at baseline , nor after therapy . Furthermore , there was no difference in change during therapy between the treatment groups . CONCLUSION There is a gradual decline in estrogen during the climacteric , and it is controversial to which extent this affects women 's mental health . The PGWB scores in this study were high before therapy , reflecting that these women without previous or current vasomotor complaints represented a selected sample . Neither short-term estrogen treatment over 12 weeks nor addition with medroxyprogesterone acetate during 2 weeks improved well-being in postmenopausal women without vasomotor symptoms who had high well-being at baseline", "OBJECTIVE : To investigate the efficacy of micro-dose transdermal estrogen in relieving menopausal vasomotor symptoms . METHODS : A r and omized , double-blind , placebo-controlled , multi-center trial . Healthy postmenopausal women with at least seven moderate or severe hot flushes per day for at least 1 week , or at least 50 per week , applied transdermal patches with a nominal delivery of 0.023 mg/d 17β-estradiol and 0.0075 mg/d levonorgestrel ( low-dose E2/levonorgestrel ; n=145 ) , 0.014 mg/d E2 ( micro-dose ; n=147 ) , or placebo ( n=133 ) for 12 weeks . The co primary efficacy variables were the mean changes from baseline in frequency and severity of moderate and severe hot flushes at the week 4 and 12 endpoints . RESULTS : At the week 12 endpoint , mean weekly frequencies of moderate and severe hot flushes were significantly reduced compared with placebo with low-dose E2/levonorgestrel ( −51.80 ; P E2 ( −38.46 ; P Severity scores were also significantly reduced with both treatments compared with placebo . At week 12 endpoint , 41.3 % of women receiving micro-dose E2 were treatment responders ( 75 % or more reduction from baseline in hot flush frequency ; P=.003 compared with 24.2 % placebo ) . In this group , the mean reduction in moderate and severe hot flushes from baseline was approximately 50 % after 2 , 70 % after 4 , 90 % after 8 , and 95 % after 12 weeks . There were no differences between active treatments and placebo regarding adverse events . CONCLUSION : Micro-dose E2 ( 0.014 mg/d ) was clinical ly and statistically significantly more effective than placebo in reducing the number of moderate and severe hot flushes , with a 41 % responder rate , supporting the concept of the lowest effective dose . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00206622 LEVEL OF EVIDENCE :", "OBJECTIVES To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day ( Estraderm MX 50 ) in postmenopausal women with moderate to severe postmenopausal symptoms . METHODS A multicenter , double-blind , r and omized , between-patient , placebo controlled trial in 109 postmenopausal women was carried out . Patches were applied twice weekly for 12 weeks . Patients were assessed at 4 , 8 and 12 weeks of treatment . The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes ( including night sweats ) per 24 h during the last 2 weeks of treatment . Other variables included Kupperman Index , local and systemic tolerability . Plasma concentrations of estradiol ( E2 ) , estrone ( E1 ) and estrone sulfate ( E1S ) were determined before and after treatment . RESULTS Estraderm MX was significantly superior to placebo ( P mean number of moderate to severe hot flushes ( including night sweats ) per 24 h after 4 , 8 and 12 weeks of treatment . The estimate of treatment group differences after 12 weeks was 4.2 hot flushes ( 95 % confidence interval : 2.6 - 5.8 ) . Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo ( P mean E2 , E1 and E1S plasma levels as expected ( E2 : baseline 2.7 pg/ml , 12 weeks 38.9 pg/ml ; E1 : baseline 18.8 pg/ml , 12 weeks 41.6 pg/ml ; E1S : baseline 235.6 pg/ml , 12 weeks 765.1 pg/ml ) . Overall rates of adverse experiences were similar for Estraderm MX and placebo . The number of patients reporting skin irritation was low and similar in both groups . CONCLUSIONS Estraderm MX 50 , a new matrix patch , offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day", "Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause", "OBJECTIVE The aim of this study was to assess pharmacists ' beliefs about bioidentical hormone therapy ( BHT ) and to identify factors influencing these beliefs . STUDY DESIGN This was a cross-sectional survey of pharmacists . An email invitation to participate in the online survey was sent to a r and om sample of 2000 pharmacists in Alberta . The survey was accessible for a six-week period from May to July , 2011 . A 54-item question naire was used to capture knowledge and beliefs about , and confidence in BHT . Summary statistics and multivariate regression were used for analyses . RESULTS Overall , 401 pharmacists completed the survey ( response rate 20 % ) . Respondents were mainly female ( 64 % ) , above 30 years of age ( 81 % ) and in practice for more than 10 years ( 63 % ) . Only 35 % of respondents correctly classified BHT as including both compounding and commercial products . In regards to beliefs , 68 % of respondents agreed that BHT is as effective as non-bioidentical hormones for vasomotor symptoms , while 60 % agreed BHT had equal risk . Beliefs on estriol , progesterone , and saliva testing however , were more diverse with many \" do not know \" responses ( 40 % ) . In multivariate analysis , pharmacists who worked in pharmacies that compounded BHT were more likely to believe in BHT safety ( p confidence with BHT ( p pharmacists had varying beliefs on BHT . In addition , beliefs on the safety of BHT were associated with pharmacists ' practice , specifically working in a pharmacy that compounds BHT . This study helps identify areas for targeted education" ]	41184e38-06ff-11f0-808a-c43d1ab1c353
A systematic review and meta- analysis was conducted of studies that address the association of bile acid ( BA ) with obesity and of studies on the effects of treatment in patients with obesity on BA metabolism , assessed from systemic BA , fibroblast growth factor 19 ( FGF19 ) , 7α-hydroxy-4-cholesten-3-one ( C4 ) level , and faecal BA . We search ed PubMed , Embase , and the Cochrane Library from inception to 1 August 2019 using the keywords obesity , obese , body mass index , and overweight with bile acid , FGF19 , FXR , and TGR5 . Two review ers independently search ed , selected , and assessed the quality of studies . Data were analysed using either fixed or r and om effect models with inverse variance weighting . Of 3771 articles , 33 papers were relevant for the association of BA with obesity of which 22 were included in the meta- analysis , and 50 papers were relevant for the effect of obesity interventions on BA of which 20 were included in the meta- analysis . Circulating fasting total BA was not associated with obesity . FGF19 was inversely and faecal BA excretion was positively associated with obesity . Roux-en-Y gastric bypass ( RYGB ) and sleeve gastrectomy ( SG ) modulated BA metabolism , ie , increased BA and FGF19 . Our results indicate that BA metabolism is altered in obesity . Certain bariatric surgeries including RYGB and SG modulate BA , whether these underlie the beneficial effect of the treatment should be investigated	[ "OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively . However , the effects of diets high in whole versus refined grains on circulating bile acids , which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor ( FXR ) and G protein-coupled bile acid receptor 1 ( TGR5 ) , have not been studied . MATERIAL S AND METHODS We conducted a secondary analysis from a r and omized controlled crossover feeding trial ( NCT00622661 ) in 80 healthy adults ( 40 women/40 men , age 18 - 45 years ) from the greater Seattle Area , half of which were normal weight ( BMI 18.5 - 25.0 kg/m2 ) and half overweight to obese ( BMI 28.0 - 39.9 kg/m2 ) . Participants consumed two four-week controlled diets in r and omized order : 1 ) a whole grain diet ( WG diet ) , design ed to be low in glycemic load ( GL ) , high in whole grains , legumes , and fruits and vegetables , and 2 ) a refined grain diet ( RG diet ) , design ed to be high GL , high in refined grains and added sugars , separated by a four-week washout period . Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography t and em mass spectrometry . Concentrations of glucose , insulin , and CRP were measured in fasting serum . Linear mixed models were used to test the effects of diet on bile acid concentrations , and determine the association between plasma bile acid concentrations and HOMA-IR and CRP . Benjamini-Hochberg false discovery rate ( FDR ) plasma bile acids were reliably detected and retained for analysis . Taurolithocholic acid ( TLCA ) , taurocholic acid ( TCA ) and glycocholic acid ( GCA ) were statistically significantly higher after the WG compared to the RG diet ( FDR association of bile acids and HOMA-IR , GCA , taurochenodeoxycholic acid , ursodeoxycholic acid ( UDCA ) , 5β‑cholanic acid‑3β,12α‑diol , 5‑cholanic acid‑3β‑ol , and glycodeoxycholic acid ( GDCA ) were statistically significantly positively associated with HOMA-IR individually , and as a group , total , 12α‑hydroxylated , primary and secondary bile acids were also significant ( FDR , chenodeoxycholic acid ( CDCA ) , cholic acid ( CA ) , UDCA , 5β-cholanic acid-3β , deoxycholic acid , and total , 12α-hydroxylated , primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals ( FDR , CA , UDCA , GDCA , glycolithocholic acid ( GLCA ) , total , primary , 12α‑hydroxylated , and glycine-conjugated bile acids were significantly associated with HOMA-IR among women , and CDCA , GDCA , and GLCA were significantly associated among men ( FDR between bile acids and CRP . CONCLUSIONS Diets with comparable macronutrient and energy composition , but differing in carbohydrate source , affected fasting plasma bile acids differently . Specifically , a diet characterized by whole grains , legumes , and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA , TCA and GCA , lig and s for FXR and TGR5 , which may have beneficial effects on glucose homeostasis", "Background Bile acids ( BAs ) are post-pr and ial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure . Total and glycine-ami date d BAs increase after sleeve gastrectomy ( SG ) and correlate to improved metabolic disease . No specific bile acid subtype has been shown conclusively to mediate the weight loss effect . Therefore , the objective of this study was to prospect ively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response . Methods Patients were prospect ively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity . Primary and secondary plasma bile acids and their ami date d ( glycine , G- , or taurine , T- ) subtypes were measured at fasting , 30 and 60 min after a liquid meal performed pre-op , and at 6 and 12 weeks post-op . Area under the curve ( AUC ) was calculated for the hour meal test for each bile acid subtype . BAs that were significantly increased post-op were correlated to body mass index ( BMI ) loss . Results Total BA AUC was significantly increased at 6 ( p total BA AUC was due to a statistically significant increase in G-BAs . Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op . Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss ( p = 0.03 ) . Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 ( p = 0.05 ) and 12 weeks ( p = 0.006 ) . Conclusions SG induced an early and persistent post-pr and ial surge in multiple bile acid subtypes . Increased G-hyocholic consistently correlated with greater early BMI loss . This study provides evidence for a role of BAs in the surgical weight loss response after SG", "Background : The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery . Methods : We prospect ively investigated the effects of the bilio-intestinal bypass ( BI-bypass ) with a wide cholecysto-jejunal anastomosis and of adjustable gastric b and ing ( AGB ) on blood lipid concentrations in obese patients . To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass , daily fecal sterol excretion was measured by gas-liquid chromatography ( GLC ) . Results : At 1 year after BI-bypass compared to baseline , the hypercholesterolemic ( n=18 ) and the normocholesterolemic ( n=19 ) patients significantly reduced total ( −38 % and −27 % , respectively ) , LDL ( −47 % and −24 % , respectively ) and HDL ( −11 % and −13 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −25 % and −13 % , respectively ) . At 1 year after AGB , the total / HDL cholesterol ratio was significantly decreased ( −11 % ) compared to baseline in hypercholesterolemic ( n=12 ) but not in normocholesterolemic ( n=6 ) patients , while total and LDL cholesterol were not affected in both groups . At 3 years after BI-bypass compared to baseline , the hypercholesterolemic ( n=9 ) and the normocholesterolemic ( n=11 ) patients significantly reduced total ( −43 % and −28 % , respectively ) and LDL ( −53 % and −29 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −38 % and −21 % , respectively ) . The BI-bypass induced a significant ( P in mean fecal cholesterol output . Conclusions : The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output . BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia", "Summary Bariatric surgery is currently the most effective procedure for the treatment of obesity . Given the role of the gut microbiota in regulating host metabolism and adiposity , we investigated the long-term effects of bariatric surgery on the microbiome of patients r and omized to Roux-en-Y gastric bypass or vertical b and ed gastroplasty and matched for weight and fat mass loss . The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and result ed in altered levels of fecal and circulating metabolites compared with obese controls . By colonizing germ-free mice with stools from the patients , we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice . These mice also had a lower respiratory quotient , indicating decreased utilization of carbohydrates as fuel . Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery", "Evidence suggests a correlation between the gut microbiota composition and weight loss caused by caloric restriction . Laparoscopic sleeve gastrectomy ( LSG ) , a surgical intervention for obesity , is classified as predominantly restrictive procedure . In this study we investigated functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very low calorie diet in ten obese subjects ( n = 5 per group ) demonstrating identical weight loss during a follow-up period of six months . For gut microbiome analysis next generation sequencing was performed and faeces were analyzed for targeted metabolomics . The energy-reabsorbing potential of the gut microbiota decreased following LSG , indicated by the Bacteroidetes/Firmicutes ratio , but increased during diet . Changes in butyrate-producing bacterial species were responsible for the Firmicutes changes in both groups . No alteration of faecal butyrate was observed , but the microbial capacity for butyrate fermentation decreased following LSG and increased following dietetic intervention . LSG result ed in enhanced faecal excretion of nonesterified fatty acids and bile acids . LSG , but not dietetic restriction , improved the obesity-associated gut microbiota composition towards a lean microbiome phenotype . Moreover , LSG increased malabsorption due to loss in energy-rich faecal substrates and impairment of bile acid circulation . This trial is registered with Clinical Trials.gov NCT01344525", "OBJECTIVE Increased delivery of bile acid salts ( BA ) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery . To further eluci date a potential role of BA in the secretion of GLP-1 and PYY , we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospect i ve , r and omized 1-year trial . DESIGN AND METHODS Patients received a st and ard test meal and blood was collected before and after eating , prior to , and 1 week , 3 months , and 12 months after surgery . RESULTS Pre-surgery , basal BA concentrations were significantly lower in bariatric patients than in healthy controls . One year post-surgery , bariatric patients expressed variably increased BA concentrations ( gastric bypass patients ∼2 fold increase , P ≤ 0.05 ) . However , whereas in both patient groups , marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery , changes in plasma BA followed a different pattern : basal and postpr and ial plasma BA concentrations increased much slower , more progressively with significant increases only 1-year post-surgery . CONCLUSIONS Based on these findings , BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients ", "Abstract Objective . Exogenous bile acid ( BA ) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass ( RYGB ) surgery . Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB , with subsequent increased fasting plasma BAs . The study assessed fasting and post-pr and ial plasma BA response before and 15 months after RYGB . Material and methods . The prospect i ve study recruited 63 obese individuals ( 43 females ) , aged 43 ( 36–56 ) [ median ( IQR ) ] years . Blood sample s were collected before and every 30 min for 120 min after a st and ard 400 kcal meal . Fasting and post-pr and ial plasma BAs , glucagons like peptide-1 ( GLP-1 ) , –tyrosine ( PYY ) , fasting C-reactive protein ( CRP ) , glucose and insulin were measured and homeostasis model assessment -insulin resistance ( HOMA-IR ) was calculated . Results . Following RYGB , body mass index , CRP , fasting glucose and HOMA-IR decreased ; 43.7 ( 39.3–49.2 ) kg/m2 to 29.2 ( 25.1–35.0 ) kg/m2 , 7.9 ( 4.1–11.9 ) mg/L to 0.4 ( 0.2–1.0 ) mg/L , 5.5 ( 5.0–6.0 ) mmol/L to 4.6 ( 4.3–4.9 ) mmol/L and 5.9 ( 3.5–9.2 ) to 1.7 ( 1.1–2.2 ) , respectively , all P 0.001 . Fasting total BAs , GLP-1 and PYY increased after RYGB ; 1.69 ( 0.70–2.56 ) µmol/L to 2.43 ( 1.23–3.82 ) µmol/L ( P = 0.02 ) , 6.8 ( 1.5–15.3 ) pmol/L to 17.1 ( 12.6–23.9 ) pmol/L ( P post-pr and ial total BAs , total glycine-conjugated BAs , GLP-1 and PYY were greater after RYGB ; 486 ( 312–732 ) µmol/L/min versus 1012 ( 684–1921 ) µmol/L/min , 315 ( 221–466 ) µmol/L/min versus 686 ( 424–877 ) µmol/L/min , 3679 ( 3162–4537 ) pmol/L/min versus 5347 ( 4727–5781 ) pmol/L/min and 1887 ( 1423–2092 ) pmol/L/min versus 3296 ( 2534–3834 ) pmol/L/min , respectively , all P in post-pr and ial plasma BA response due to larger amounts of glycine-conjugated BAs . This suggests up regulation of BA production and conjugation after RYGB", "BACKGROUND Bile acids have been proposed as key mediators of the metabolic effects after bariatric surgery . Currently no reports on bile acid profiles after duodenal switch exist , and long-term data after gastric bypass are lacking . OBJECTIVE To investigate bile acid profiles up to 5 years after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch and to explore the relationship among bile acids and weight loss , lipid profile , and glucose metabolism . SETTING S Two Sc and inavian University Hospitals . METHODS We present data from a r and omized clinical trial of 60 patients with body mass index 50 - 60 kg/m2 operated with gastric bypass or duodenal switch . Repeated measurements of total and individual bile acids from fasting serum during 5 years after surgery were performed . RESULTS Mean concentrations of total bile acids increased from 2.3 µmol/L ( 95 % confidence interval [ CI ] , -.1 to 4.7 ) at baseline to 5.9 µmol/L ( 3.5 - 8.3 ) 5 years after gastric bypass and from 1.0 µmol/L ( 95 % CI , -1.4 to 3.5 ) to 9.5 µmol/L ( 95 % CI , 7.1 - 11.9 ) after duodenal switch ; mean between-group difference was -4.8 µmol/L ( 95 % CI , -9.3 to -.3 ) , P = .036 . Mean concentrations of primary bile acids increased more after duodenal switch , whereas secondary bile acids increased proportionally across the groups . Higher levels of total bile acids at 5 years were associated with lower body mass index , greater weight loss , and lower total cholesterol . CONCLUSIONS Total bile acid concentrations increased substantially over 5 years after both gastric bypass and duodenal switch , with greater increases in total and primary bile acids after duodenal switch . ( Surg Obes Relat Dis 2017;0:000 - 000 . ) © 2017 American Society for Metabolic and Bariatric Surgery . All rights reserved", "A previous study surprisingly showed that after jejunoileal bypass a ratio of 1:3 compared with 3:1 between the jejunal and ileal segment left in continuity result ed in a smaller synthesis rate , pool size , and postcibal jejunal levels of bile acids . These findings are reevaluated in the present study of 34 patients who either were waiting for or 3 , 9 , or 15 months earlier , had undergone bypass surgery with a 3:1 or 1:3 jejunoileal ratio . Compared with 3:1 bypass , the 1:3 bypass result ed in ( i ) greater reduction of the fasting bile acid pool , significant for chenodeoxycholic acid but not for cholic adic , ( ii ) less increase in synthesis rate of both bile acids , ( iii ) less decrease in relative content of taurine-conjugated bile acids in bile , and ( iv ) equal reduction of postcibal levels of bile acids in jejunum . We conclude that the increase in synthesis of bile acids compensates insufficiently for the excess fecal loss ; the lower synthesis rate after bypass with a short jejunum relative to ileum in function may be due to an impaired stumulation of bile acid synthesis , the mechanism of which is unexplained", "OBJECTIVES : Orlistat , an intestinal lipase inhibitor , has recently been approved by the US Food and Drug Administration for treatment of obesity . The effects of orlistat on hepatobiliary function have not been previously defined . A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet . METHODS : A total of 23 obese ( BMI 30–41 kg/m2 ) subjects were r and omized to a double blind t.i.d . treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet ( 1200–1500 kcal/day ) . The study was design ed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat . Cholesterol saturation , bile composition , and gallbladder motility were measured . RESULTS : At the end of the treatment period , mean weight loss of 3.8 kg was achieved in the orlistat group ( vs 2.3 kg with placebo , p = NS ) . Total bile acid concentration decreased significantly with placebo ( –18.57 ± 6.99 mmol/L ; 95 % CI = –32.26 to –4.87 ) , but not with orlistat . Biliary phospholipid concentration decreased significantly with placebo ( −4.38 ± 1.91 mmol/L ; 95 % CI = –8.13 to –0.64 ) but not with orlistat . Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups . Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group . CONCLUSIONS : Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids . Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function . We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat ", "Previous suggested , surprisingly , that after jejunoileal bypass surgery the lithogenicity of the bile , assessed by its cholesterol saturation and rate of gallstone formation , increases more with a 1:3 than with a 3:1 jejunoileal ratio of the functioning segment . The present study re-evaluates this by examining fasting bile sample s drawn from duodenum after cholecystokinin stimulation in 34 obese patients without gallstones , who either were waiting for or had had bypass surgery , with a 1:3 or 3:1 jejunoileal ratio , 3,9 , or 15 months earlier . In all groups , the cholesterol content exceeded the solubilizing capacity of the bile as determined on the basis of total lipid concentration and content of phospholipid relative to bile acids . The cholesterol supersaturation increased with bypass surgery as such , increased more with a 1:3 than with a 3:1 jejunoileal ratio , decreased with time after surgery , and reached the preoperative level at 15 months . Assuming a total lipid concentration of 10 g/dl in the bile did not change this pattern . Our results indicate that during the period of weight loss after bypass surgery the lithogenicity of gallbladder bile increases more with a 1:3 than with a 3:1 jejunoileal ratio", "BACKGROUND Bariatric surgery is the most effective treatment alternative in morbid obesity . The mechanisms contributing to these benefits remain poorly understood . Bile acids ( BAs ) are mediators of different regulatory functions in glucose and cholesterol homeostasis and energy expenditure . Recent evidence suggests that BAs are critically important for the beneficial effects of sleeve gastrectomy ( SG ) . OBJECTIVES The aim of this study was to evaluate the effect of SG on BA synthesis . SETTING University Hospital . Santiago , Chile . METHODS Obese patients were evaluated before and after SG ( 1 , 3 , 6 , and 12 months ) . BA synthesis was evaluated through the serum marker , 7 α-hydroxy-4-cholesten-3-one ( C4 ) . Primary and secondary BA and C4 were determined by high performance liquid chromatography coupled with t and em mass spectrometry detection ( HPLC-MS/MS ) . RESULTS From June 2013 to January 2014 , 19 patients ( age 37.6±7.8 years ; BMI 35.8±3.5 kg/m(2 ) ; 79 % female ) were included in this study . Mean weight loss at 1 , 3 , 6 , and 12 months was 11.3 , 17.5 , 23.6 , and 25.4 kg , respectively , equivalent to 11.8 , 18.6 , 24.8 , and 26.9 of total body water percentage ( % TBW ) ( P ) . Serum C4 levels at baseline , 1 , 3 , 6 , and 12 months were 23.4±21.1 , 4.9±8.2 , 8.7±12.1 , 13.8±12.9 , and 18.8±16.8 ng/mL ( P respectively . Fibroblast growth factor 19 ( FGF19 ) levels at baseline , 1 , 3 , 6 , and 12 months were 71±33.3 , 130.5±66.2 , 117.8±57.2 , 134.6±91.7 , and 124.3±85.9 pg/mL ( P = .019 ) , respectively . CONCLUSION Serum levels of C4 decrease after SG , indicating a reduction in the synthesis of BA . FGF19 may play a role in decreasing BA synthesis . Further studies are necessary to characterize the effect of bariatric surgery on BA homeostasis", "BACKGROUND & AIMS Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity . Because of orlistat 's mode of action , increased fecal fat is presented to the colonic mucosa , and fecal bile acid and free fatty acid composition may be altered during treatment . Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation . METHODS Twenty-four obese ( body mass index , 30 - 40 kg/m2 ) but otherwise healthy male and female subjects were enrolled in a single-center , r and omized , double-blind , placebo-controlled , parallel-group study . Participants were hospitalized during days 1 - 3 and 33 - 42 of treatment and were treated as out patients for the remaining days . RESULTS Treatment with orlistat for 6 weeks result ed in significantly greater increases in fecal weight , total fecal fat , and fecal free fatty acids than placebo . Total fecal bile acid amounts decreased slightly with orlistat , and increased significantly with placebo treatment ( P Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices ( 5-bromo-2-deoxyuridine , whole crypt mitotic count , and proliferating cell nuclear antigen ) . CONCLUSIONS Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation , a putative biomarker of colon cancer risk", "Jejunoileal bypass may impair liver function . The hypothesis of the present study was that this may depend on the jejunoileal ratio of the segment left in continuity in a manner that affects the transport of bile acids from blood to bile . We investigated five extremely obese patients before and 29 patients 3 , 9 and 15 months after bypass surgery with a 3:1 or 1:3 jejunoileal ratio of the functioning segment . Routine liver function tests , plasma disappearance rate of intravenously administered 3H-cholic acid and 14C-24-chenodeoxycholic acid , and fasting and postpr and ial serum concentrations of total 3-alpha-hydroxy bile acids showed no appreciable significant relationship with bypass surgery as such , time after surgery , or the jejunoileal ratio of the functioning segment", "CONTEXT It has been hypothesized that increased plasma bile acids ( BAs ) contribute to metabolic improvements after Roux-en-Y gastric bypass ( RYGB ) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones . OBJECTIVE The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis ( insulin secretion and sensitivity ) and energy metabolism ( resting energy expenditure and thyroid hormone axis ) . DESIGN , PARTICIPANTS , INTERVENTION , AND MAIN OUTCOME MEASURE : Eighteen extremely obese subjects were studied before and after 20 % weight loss , induced by either laparoscopic adjustable gastric b and ing ( LAGB ) ( n = 10 ) or RYGB surgery ( n = 8) . RESULTS Plasma BAs more than doubled after RYGB [ fasting : 1.08 ( 0.26 - 1.42 ) to 2.28 ( 1.59 - 3.28 ) μmol/L , P = .03 ; postpr and ial : 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L , P = .01 ] but were either lower or did not change after LAGB [ fasting : 1.80 ( 1.49 - 2.19 ) to 0.92 ( 0.73 - 1.15 ) μmol/L , P = .02 ; postpr and ial : 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L , P = .14 ] . Skeletal muscle expression of TGR5 targets , Kir6.2 and cyclooxygenase IV , increased after RYGB but not LAGB . Surgery-induced changes in BAs were associated with increased peak postpr and ial plasma glucagon-like peptide-1 ( r(2 ) = 0.509 , P = .001 ) and decreased serum TSH ( r(2 ) = 0.562 , P the change in insulin response to a meal ( r(2 ) = 0.013 , P = .658 ) , insulin sensitivity ( assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure ) ( r(2 ) = 0.001 , P = .995 ) , or resting energy expenditure ( r(2 ) = 0.004 , P = .807 ) . CONCLUSIONS Compared with LAGB , RYGB increases circulating BAs and TGR5 signaling , but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism" ]	41184eba-06ff-11f0-808a-c43d1ab1c353
Obesity continues to increase in prevalence worldwide . Hypertension has long been associated with obesity , and weight loss continues to be a first-line therapy in the treatment of hypertension . Lifestyle modification and pharmacologic therapy , however , often meet with treatment failure . Bariatric surgery continues to be the most successful approach to sustained weight loss . This review focuses on the underlying physiologic mechanisms of obesity-hypertension , and the impact of bariatric surgery on the treatment of hypertension . Current available literature on the physiologic mechanisms of obesity-hypertension , and the major trials , meta-analyses and systematic review s of the impact of bariatric surgery procedures on hypertension are review ed . Evidence suggests significant improvement in obesity-hypertension in patients who undergo surgical weight-reduction procedures . Malabsorptive techniques such as the Roux-en-Y gastric bypass or surgical resection techniques such as laparoscopic sleeve gastrectomy appear to offer superior results in regards to hypertension control over restrictive techniques such as Gastric B and ing . Though long-term control of hypertension following surgery remains a concern , available follow-up post-operative data of up to 10 years suggests a sustained , if lessened , effect on hypertension control over time	[ "Background / Objectives . Embolization of the left gastric artery ( LGA ) , which preferentially supplies the gastric fundus , has been shown to produce weight loss in animal models . However , weight loss after LGA embolization in humans has not been previously established . The aim of this study was to evaluate postprocedural weight loss in patients following LGA embolization . Subjects/ Methods . A retrospective analysis of the medical records of patients who underwent LGA embolization for upper gastrointestinal ( GI ) bleeding was performed . Postprocedural weight loss in this group was compared to a control group of patients who had undergone embolization of other arteries for upper GI bleeding . Results . The experimental group ( N = 19 ) lost an average of 7.3 % of their initial body weight within three months of LGA embolization , which was significantly greater than the 2 % weight loss observed in the control group ( N = 28 ) ( P = 0.006 ) . No significant differences were seen between the groups in preprocedural body mass index ( BMI ) , age , postprocedural care in the intensive care unit , history of malignancy , serum creatinine , or left ventricular ejection fraction . Conclusions . The current data suggest that body weight in humans may be modulated via LGA embolization . Continued research is warranted with prospect i ve studies to further investigate this phenomenon", "Overweight patients with uncomplicated essential hypertension were followed up biweekly for six months : 24 not receiving antihypertensive-drug therapy ( Group I ) and 83 on regular but inadequate ( despite drug manipulation ) antihypertensive-drug therapy ( Group II ) . All patients in Group I and 57 r and omly selected patients from group II ( IIa ) participated in a weight-reduction program . The remaining 26 from Group II ( IIb ) did not receive a dietary program . Salt intake was in the normal range in all three groups . All patients on the dietary program lost at least 3 kg ( mean , 10.5 kg ) , and all but two showed a meaningful reduction in blood pressure ; 75 per cent of Group I and 61 per cent of Group IIa returned to normal blood pressure . The weight and blood-pressure reductions were highly significant ( P less than 0.001 ) , were present in both sexes and all ages , and were directly associated . In Group IIb , no significant change in blood pressure or weight occurred ( P greater than 0.30 )", "Objectives To investigate plasma total ghrelin and obestatin levels and the ghrelin/obestatin ratio prospect ively , in hypertensive obese patients . Methods Height , weight , and waist and hip circumferences were measured in hypertensive and normotensive obese patients and matched healthy controls ; the body mass index and waist to hip ratio were calculated . Fasting glucose and insulin levels were measured and the homeostasis model assessment of insulin resistance ( HOMA-IR ) was determined . Fasting ghrelin and obestatin concentrations were measured by radioimmunoassay and the ghrelin/obestatin ratio was calculated . Results A total of 38 hypertensive obese patients , 40 normotensive obese patients and 38 controls were enrolled . Hypertensive obese patients had lower plasma levels of ghrelin and obestatin than normotensive obese patients or controls . In addition , normotensive obese patients had lower plasma ghrelin and obestatin levels than controls . In hypertensive obese patients , ghrelin and obestatin levels were negatively associated with systolic and diastolic blood pressure , fasting insulin and HOMA-IR . In normotensive obese patients , ghrelin , obestatin and the ghrelin/obestatin ratio were negatively associated with fasting insulin and HOMA-IR . In both patient groups , fasting obestatin and ghrelin concentrations were significantly and positively correlated with each other . Conclusion Changes in the levels of ghrelin and obestatin may play a role in the pathophysiology of obesity and hypertension", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline", "Objective To compare two bariatric surgical principles with regard to effects on blood pressure and salt intake . Background In most patients bariatric surgery induces a sustained weight loss and a reduced cardiovascular risk profile but the long-term effect on blood pressure is uncertain . Methods Cohort study with data from the prospect i ve , controlled Swedish Obese Subjects ( SOS ) study involving 480 primary health care centres and 25 surgical departments in Sweden . Obese patients treated with non-surgical methods ( Controls , n = 1636 and n = 1132 at 2 y and 10 y follow up , respectively ) were compared to patients treated with gastric bypass ( GBP , n = 245 and n = 277 , respectively ) or purely restrictive procedures ( vertical b and ed gastroplasty or gastric b and ing ; VBG/B , n = 1534 and n = 1064 , respectively ) . Results At long-term follow-up ( median 10 y ) GBP was associated with lowered systolic ( mean : −5.1 mm Hg ) and diastolic pressure ( −5.6 mmHg ) differing significantly from both VBG/B ( −1.5 and −2.1 mmHg , respectively ; p Diurnal urinary output was + 100 ml ( P Urinary output was linearly associated with blood pressure only after GBP and these patients consumed approximately 1 g salt per day more at the follow-ups than did VBG/B ( P transient blood pressure lowering effect , whereas gastric bypass was associated with a sustained blood pressure reduction and an increased diuresis . The daily salt consumption was higher after gastric bypass than after restrictive bariatric surgery", "OBJECTIVES To determine relationship of intra-abdominal pressure to central obesity and the comorbidity of obesity . DESIGN Non-r and omized , prospect i ve . SETTING University hospital , operating room . SUBJECTS Eighty-four anaesthetized consecutive patients prior to gastric bypass for morbid obesity and five non-obese patients before colectomy for ulcerative colitis . MAIN OUTCOME MEASURES Weight , body mass index ( BMI ) , co-morbid history , sagittal abdominal diameter , waist : hip ( W : H ) ratio and urinary bladder pressure , as an estimate of intra-abdominal pressure . RESULTS Urinary bladder pressure was greater in the obese than the non-obese ( 18 + /- 0.7 vs. 7 + /- 1.6 cm H2O , P ( hypoventilation , gastroesophageal reflux , venous stasis , stress incontinence , incisional hernia ) or possibly ( hypertension , diabetes ) due to increased abdominal pressure . W : H ratio correlated with urinary bladder pressure in men ( r = + 0.6 , P intraabdominal pressure which contributed to obesity-related comorbidity . W : H ratio was not a reliable indicator of intra-abdominal pressure for women who often have both peripheral and central obesity . Further studies are needed to evaluate the relationship between intra-abdominal pressure and Type II diabetes and hypertension", "Background Laparoscopic Roux-en-Y gastric bypass ( LRYGB ) is the most common bariatric technique . Laparoscopic sleeve gastrectomy ( LSG ) is a restrictive procedure ; the metabolic and endocrine effects of which remain unknown . We compared the effects of both procedures on glucose metabolism and fasting and meal-stimulated gut hormone levels . Methods Seven patients were r and omised to LRYGB and eight to LSG . All patients were evaluated before and at 3 and 12 months postoperatively . Plasma levels of glucose , insulin , ghrelin , leptin , peptide YY ( PYY ) , GLP-1 and pancreatic polypeptide were measured before and after 10 and 60 min of a st and ard test meal ingestion . Results Age , body mass index and preoperative hormone levels were similar in both groups . A significant reduction of plasma glucose and insulin levels was observed after surgery . Moreover , a normalisation of homeostatic model assessment for insulin resistance value was also seen after both procedures . The fasting and postpr and ial leptin levels were significantly lower in the LRYGB group . LSG was followed by a significant reduction in fasting ghrelin levels . In the LRYGB group , GLP-1 levels increased significantly after the test meal . Conclusions LRYGB and LSG markedly improved glucose homeostasis . Only LSG decreased fasting and postpr and ial ghrelin levels , whereas GLP-1 and PYY levels increased similarly after both procedures", "Purpose This study examines the effect of Roux-en-Y gastric bypass ( RYGB ) and laparoscopic adjustable gastric b and ing ( LAGB ) on renal function for at least 5 years post-operatively in a tertiary referral center for bariatric surgery . Material s and Methods This prospect i ve cohort study of patients undergoing RYGB and LAGB measured renal function , blood pressure , and diabetes status pre-operatively and then 1 and 5 years post-operatively . Renal function was assessed using the Modification of Diet in Renal Disease ( MDRD ) , Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) , and Cockcroft-Gault formulae . Hypertension and diabetes were defined by the European Society of Hypertension and European Society of Cardiology joint guidelines and American Diabetes Association guidelines , respectively . A sub-group who had completed 10 years post-operative follow-up was also included . Results Estimated glomerular filtration rate ( eGFR ) increased over 5 years after RYGB ( N = 190 ; 94 ± 2 mL/min/1.73 m2 to 102 ± 22 mL/min/1.73 m2 , p = 0.01 ) and LAGB ( N = 271 ; 88 ± 1 to 93 ± 22 mL/min/1.73 m2 , p = 0.02 ) . In a sub-group with up to 10 years post-operative date , this trend was maintained . In patients with renal impairment , eGFR improved over 5 years ( 52 ± 2 to 68 ± 7 mL/min/1.73 m2 , p = 0.01).Remission of hypertension was greater after RYGB than LAGB at 1 year ( 32 vs. 16 % , p = 0.008 ) and at 5 years post-operatively ( 23 vs. 11 % , p = 0.02 ) . Conclusions Bariatric surgery stabilizes eGFR post-operatively for at least 5 years . In a sub-group with renal impairment , eGFR is increased in the first post-operative year and this is maintained for up to 5 years . RYGB is an effective procedure in achieving blood pressure control " ]	41184f32-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer ( T1 - 4 , N1 - 2 , M0 ) . OPTIONS Neoadjuvant or adjuvant treatments compared with " curative " surgery alone . OUTCOMES Overall survival , disease-free survival , and adverse effects . EVIDENCE The MEDLINE , CANCERLIT and Cochrane Library data bases and relevant conference proceedings were search ed to identify r and omized trials . VALUES Evidence was selected and review ed by one member of the Cancer Care Ontario Practice Guidelines Initiative ( CCOPGI ) Gastrointestinal Cancer Disease Site Group and method ologists . A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice , to develop an evidence -based practice guideline . This report has been review ed and approved by the Gastrointestinal Cancer Disease Site Group , comprising medical oncologists , radiation oncologists , surgeons , a pathologist and 2 community representatives . BENEFITS , HARMS AND COSTS When compared with surgery alone , at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9 % ( 50 % v. 41 % , p = 0.005 ) and to improve relapse-free survival from 31 % to 48 % ( p = 0.001 ) . At 5 years , it has been shown to increase overall survival by 11.6 % ( 40 % v. 28.4 % ) and to improve relapse-free survival from 25 % to 38 % ( p toxic deaths in 1 % of patients . The most frequent adverse effects ( > grade 3 [ Southwest Oncology Group toxicity scale ] are hematologic ( 54 % ) , gastrointestinal ( 33 % ) , influenza-like ( 9 % ) , infectious ( 6 % ) and neurologic ( 4 % ) . The radiation fields used can possibly damage the left kidney , result ing in hypertension and other renal problems . Furthermore , this therapy could increase the dem and on radiation re sources . Physicians and patients should underst and the tradeoffs between survival benefit and toxicity and cost before making treatment decisions . RECOMMENDATIONS After surgical resection , patients whose tumours have penetrated the muscularis propria or involve regional lymph nodes should be considered for adjuvant combined chemoradiotherapy . The current st and ard protocol consists of 1 cycle of 5-fluorouracil ( 5-FU ) ( 425 mg/m2 daily ) and leucovorin ( 20 mg/m2 daily ) administered daily for 5 days , followed 1 month later by 45 Gy ( 1.8 Gy/d ) of radiation given with 5-FU ( 400 mg/m2 daily ) and leucovorin ( 20 mg/m2 daily ) on days 1 through 4 and the last 3 days of radiation . One month after completion of radiation , 2 cycles of 5-FU ( 425 mg/m2 daily ) and leucovorin ( 20 mg/m2 daily ) in a daily regimen for 5 days are given at monthly intervals . There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria . For patients unable to undergo radiation , adjuvant chemotherapy alone may be of benefit , particularly for those with lymph-node metastases . The optimal regimen remains to be defined . There is insufficient evidence from r and omized trials to recommend neoadjuvant chemotherapy , or neoadjuvant or adjuvant radiotherapy or immunotherapy , either alone or in combination , outside a clinical trial . VALIDATION A draft version of this document was circulated to 166 clinicians using a 21-item feedback question naire . Ninety-nine ( 63 % ) returned the question naire , and 74 of these indicated that the guideline was relevant to their clinical practice and completed the survey . Of the 74 clinicians , 52 ( 70 % ) agreed that the document should be approved as a practice guideline . SPONSORS The CCOPGI is supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care	[ "One hundred forty‐two patients with all stages of gastric carcinoma were prospect ively stratified into two divisions according to T.N.M. stage following , but irrespective of the type of surgical procedure . Division I ( T 1‐3 , N 1‐2 , M O ) was r and omized into a control group , and a treatment group who received 2000 rad in 8 fractions over 10 days with intravenous 5 Fluorouracil ( 5 F.U. ) at a dose of 500 mg daily × 4 days preirradiation and then 12.5 mg/kg daily for 5 days every 28 days for six courses . Division II ( T4 or M1 ) was r and omized into three groups ; a control group , a group who received radiotherapy and 5 F.U. in the same schedule as division one and a group who received Thiotepa 45 mg intravenously daily for three days and then every 28 days for 6 months . Four and one‐half years after commencement of the trial 86 % of the patients had died . There was no difference in survival rate between the treatment and control groups , ( p > 0.5 ) in Division I or II . Survival appeared to correlate with the T.N.M. stage of disease and not therapy . Blind assessment of the quality of life showed no difference between the treatment groups and the controls . In the dose schedules used , this form of oncological therapy had no efect on survival or quality of life in patients with gastric carcinoma . Cancer 44:385‐391 , 1979", "In this prospect ively r and om study , the effect of oral Ftorafur as an adjuvant chemotherapy was compared with that of oral placebo in patients with Stage II and Stage III gastric cancer . Patients had undergone a subtotal gastrectomy with a resection margin that should have been free of tumors . Ftorafur ( 10 mg/kg ) was given daily to 59 Group A patients . Multiple vitamins were given twice a week to 56 Group B patients . We found that there was no statistical significance in Stage II patients with regard to survival . In Stage III patients , those treated with oral Ftorafur had better 3-year and 5-year survival rates than those receiving oral placebo . This preliminary report on this ongoing study seems to indicate that long-term postoperative Ftorafur treatment may be beneficial to Stage III gastric cancer patients", " Summary Two hundred and seventeen patients with advanced gastric cancer were classified according to the resectability of the tumour into two groups : I , resectable ( non-radical surgery ) , 99 patients , and II , non-resectable carcinoma , 118 patients . Within each group patients were r and omly assigned to receive 5-fluorouracil ( 5-FU ) + BCG , 5-FU , or no further treatment ( surgery only ) . BCG was given by scarification . A 2-year follow-up is reported . The group of patients with resectable tumours and receiving chemoimmunotherapy had a statistically significant prolongation of survival compared with the 5-FU and surgery only groups . No differences in survival were observed between these treatment modalities in patients with non-resectable tumour . These observations indicate that chemoimmunotherapy may be of benefit for a selected group of patients with gastric cancer", "Combination chemotherapy ( CT ) has , in some groups of patients with gastric cancer ( GC ) , who are at a high risk for relapse , result ed in a small but measurable improvement in palliation and patient survival not reaching statistical significance and therefore remaining applicable in an investigational setting . Based on the above data , we studied adjuvant CT with FEM ( 5-fluorouracil ( 5-FU ) , epirubicin , mitomycin C ) in a r and omized study of patients with completely resected stage III GC and patients with stages T1 - 3 with a low histologic grade . CT was started 2 - 3 weeks after surgery . From August 1988 until February 1994 , 84 patients with completely resected tumors and lymph nodes were r and omized to either group A ( FEM ) or group B ( no treatment ) . Patients were eligible for r and omization if they had a Karnofsky score > 60 , no postoperative evidence of residual tumor , and normal cardiac , hepatic and renal functions . Forty-two patients were r and omized to each group , with no significant differences regarding : age distribution , group A 53 years ( 41 - 65 ) , group B 57 years ( 35 - 66 ) ; sex , group A 32/10 , group B 25/17 ( men/women ) ; site of primary tumor , group A 22/20 , group B 25/17 ( pylorus/antrum ) ; histologic grade , group A 0/19/23 , group B 0/25/17 ( grade s I/II/III ) ; lymph node metastases , group A 30 , group B 32 , and surgical procedure , group A 33/9/6 , group B 35/7/9 ( total gastrectomy/partial gastrectomy/splenectomy ) . Group A received 5-FU 600 mg/m2/day i.v . on days 1 , 8 , 29 and 36 , epirubicin 45 mg/m2/day i.v . on days 1 and 29 , and mitomycin C 10 mg/m2 i.v . on day 1 . The schedule was repeated every 56 days for 3 cycles . Group B received no treatment odd was only subjected to the regular follow-up . At the last follow-up at 66 months , 27/42 patients in group A ( 64 % ) had relapsed or died , compared to 34/42 patients in group B ( 81 % ) . The differences in the relapse and the disease-free and the overall survival rates were not statistically significant . Only the subgroup of patients with histologic grade III tumors receiving adjuvant FEM demonstrated a trend towards improved survival ( p = 0.085 ) . Main therapy-related toxicities for the treatment group were grade I-II anemia , neutropenia , and throbocytopenia in 16 , 45 , and 22 % of patients , respectively , and grade I-II nausea and vomiting in 29 % of patients . Based on the present findings and those of previous studies , even if one considers the difference reaching statistical significance in the latter for histologic grade III tumors , it becomes evident that with current therapeutic modalities adjuvant therapy has no established role in the management of resectable GC . Studies of new-generation regimens , such as FAMTX ( 5-FU , Adriamycin and methotrexate ) as well as ELF ( etoposide , Leucoverin , and 5-FU ) , should be conducted in the adjuvant therapy setting with a nontherapy control group , in order to clarify the issue of adjuvant CT in resectable GC", "Sixty-eight patients admitted for resection of gastric carcinoma entered a prospect ively r and omized trial . Patients in the therapy group ( n = 34 ) received a preoperative controlled infusion of 10 mg Propionibacterium avidum KP-40 . The therapy and control group did not differ with regard to postoperative complications , tumor recurrence rates ( therapy group : 41 % , control group : 38 % ) , and patient survival rates ( survival rate in the therapy group after 25 months : 53 % , in the control group after 25 months : 50 % )", "From September 1979 through March 1981 , a total of 302 patients with gastric cancer and undergoing gastrectomy at the Department of Surgery at Chiba University Hospital and its 14 affiliated hospitals was studied for clinical effectiveness of immunotherapy with Nocardia rubra cell wall skeleton . The patients were stratified by gross stage of cancer and degree of operative curability . They were then assigned r and omly to either chemotherapy group or chemotherapy plus immunotherapy group . Immunotherapy used was intradermal injection of 400 micrograms of N. rubra cell wall skeleton which was given weekly for the first month and monthly thereafter . After the specimen was examined microscopically , the patients were classified by histological stage of cancer and radicality of surgical intervention into curative or noncurative groups . The patients were surveyed for survival period in December 1981 . The postoperative survival rate was compared in patients of histologically curative or noncurative resection cases between the two treatment groups . No statistical difference was detected between the groups in age , sex , or operative procedures that might influence the patient 's survival . As a result , statistical intergroup difference in survival rates was not seen in patients of the curative group , probably due to a short observation period . However , the intergroup difference in survival rates was statistically significant in patients of the noncurative group ( p less than 0.01 ) . These results indicate the adjunctive effect of N. rubra cell wall skeleton as an immunotherapeutic agent in patients undergoing gastrectomy for gastric cancer", "BACKGROUND In Japan the surgical approach to treatment of potentially curable gastric cancer , including extended lymphadenectomy , seems in retrospective surveys to give better results than the less radical procedures favoured in Western countries . There has , however , been no evidence from r and omised trials that extended lymphadenectomy ( D2 gastric resection ) confers a survival advantage . This question was addressed in a trial involving thirty-two surgeons in Europe . METHODS In a prospect i ve r and omised controlled trial , D1 resection ( level 1 lymphadenectomy ) was compared with D2 resection ( levels 1 and 2 lymphadenectomy ) . Central r and omisation ( 200 patients in each arm ) followed a staging laparotomy . FINDINGS The D2 group had greater postoperative hospital mortality ( 13 % vs 6.5 % ; p=0.04 [ 95 % Cl 9 - 18 % for D2 , 4 - 11 % for D1 ] and higher overall postoperative morbidity ( 46 % vs 28 % ; p postoperative stay was also longer . The excess postoperative morbidity and mortality in the D2 group was accounted for by distal pancreaticosplenectomy and splenectomy . In the whole group ( 400 patients ) , survival beyond three years was 30 % in patients whose gastrectomy included en-bloc pancreatico-splenic resection versus 50 % in the remainder . INTERPRETATION D2 gastric resections are followed by higher morbidity and mortality than D1 resections . These disadvantages are consequent upon additional pancreatectomies and distal splenectomies , and in long-term follow-up the higher mortality when the pancreas and spleen are resected may prove to Noneify any survival benefit from D2 procedures", "After en bloc resection of gastric adenocarcinoma , 180 patients were r and omized to 2 years of 5‐fluorouracil ( 5‐FU ) + semustine ( MeCCNU ) chemotherapy or to observation only . After a median follow‐up time of 64 months , 48 of 89 control patients and 51/91 treated patients recurred ( P recurrent cancer were similar for both groups : liver , 32 % ; local esophagus or stomach , 51 % ; abdominal nodes and peritoneum , 38 % ; and extra‐abdominal nodes , 14 % . The survival curves overlap ; 51/89 controls and 57/91 treated patients died with a median survival of 32.7 and 36.6 months , respectively ( P experienced clinical ly important hematologic toxicity and two treated patients died of marrow failure with leukemia . Because of the toxicity and the lack of effectiveness , adjuvant 5‐FU + MeCCNU is not recommended for patients with resectable gastric cancer", "OBJECTIVE Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy . This r and omized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer . SUMMARY BACKGROUND DATA Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients . Resection site and peritoneal surface spread , along with liver metastases , are the most common areas of recurrence . Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced . METHODS In a prospect i ve r and omized trial of 248 patients , intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection . Patients who were thought to have stage II or stage III disease were r and omized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy . After final pathologic examinations , there were 39 patients with stage I , 50 with stage II 95 with stage III , and 64 with resected stage IV cancer . RESULTS The 5-year survival of the surgery-only group was 29.3 % , and the surgery-plus-intraperitoneal chemotherapy group was 38.7 % ( p = 0.219 ) . In a subset analysis , the patients with stage I , stage II , and stage IV disease showed no statistically significant difference in survival . The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4 % versus a survival rate of 49.1 % for patients who underwent surgery plus intraperitoneal chemotherapy ( p = 0.011 ) . CONCLUSIONS In a subset analysis , patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy . Further studies in patients with gastric cancer with surgically directed chemotherapy are suggested", "Sixty-two patients with resectable but poor-prognosis gastric carcinoma were r and omized to either no surgical adjuvant therapy or treatment with 5-fluorouracil ( 15 mg/kg by rapid intravenous injection X 3 ) plus radiation ( 3,750 rad in 24 fractions ) initiated 3 1/2 to six weeks postoperatively . Informed consent was obtained after r and omization and only from the 39 r and omized to treatment . Ten patients refused their treatment assignment . The five-year survival rate for patients r and omized to treatment was 23 % , and for those r and omized to no treatment , 4 % ( P less than .05 ) . Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups ( P = .024 ) and favored treatment assignment . When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing , five-year survival rates were : treated , 20 % ; treatment refusal , 30 % ; controls , 4 % ; the three survival distributions were not significantly different . Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54 % of those who received no treatment . This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research . This study also illustrates the potential problems that may be encountered in interpreting results when patients are r and omized to a study before consent is obtained", "In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a r and omised trial on 134 patients in two arms : a control one with no further treatment after surgery versus a treatment arm given mitomycin-C ( MMC ) , 20 mg/m2 intravenously one day every 6 weeks for four courses , starting before the sixth week after surgery . The median follow-up was 105 months . In the control arm , 49 out of 66 patients died due to recurrence , versus 40 out of 68 patients in treatment arm . Actuarial survival curve was statistically significant ( P Liver metastases were lower in adjuvant group than in the control group ( 8/68 versus 19/66 ) . Toxicity was mild . Main toxic effects were thrombocytopenia , leukopenia , nausea and vomiting . A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed . In that particular case MMC was given after surgery . We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery , improves survival rate in gastric cancer resected patients", "Adjuvant immunochemotherapy using schizophyllan ( SPG ) , an extract from the culture broth ofSchizophyllum commune Fries , was prescribed at r and om for 326 Japanese patients with resectable gastric cancer . The overall survival rates for 3 years did not differ between the SPG and control groups . In 62 patients with stage I gastric cancer and 67 with stage II , there was little difference in the 3-year survival rates . The survival rates for 100 patients with stage III were enhanced at p=0.0811 in the SPG group , as compared to the controls . The survival rates in 97 patients with stage IV cancer were much the same . These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer", " 5‐Fluorodeoxyuridine was administered to 185 patients r and omized to the treated group following gastric resection for carcinoma of the stomach . Two hundred twelve patients were r and omized to control groups . There are no significant differences in operative mortality , complications , or 3‐year survival rates", "Summary Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a r and omized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer . The British Stomach Cancer Group conducted a r and omized , double-blind , placebo-controlled trial examining the effects of cimetidine ( 400 mg or 800 mg twice a day ) on the survival of patients with early ( stages I , II and III : n = 229 ) and advanced ( stages IVa and IVb : n = 201 ) gastric cancer . The primary end point was death . A total of 442 patients were r and omized by 59 consultants in 39 hospitals between February 1990 and March 1995 . Log-rank survival analysis was used to assess differences between the groups . Three hundred and forty patients died during the study : 166 ( 49 % ) in the cimetidine treatment groups and 174 ( 51 % ) in the placebo groups . Median survival for patients receiving cimetidine was 13 months ( 95 % confidence interval ( CI ) 9–16 months ) and 11 months in the placebo arm ( 95 % CI 9–14 months ) . There was no significant difference in survival between the two treatment groups ( P = 0.42 ) or between different doses of cimetidine tablets ( P = 0.46 ) . Five-year survival of those patients r and omized to cimetidine was 21 % compared to 18 % for those patients r and omized to placebo . Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo", "Summary The usefulness of LMS in postoperative immunochemotherapy of gastric cancer was investigated . In compliance with the protocol , MMC was given at a dose of 20 mg on the day of gastrectomy , and an additional 10 mg on the next day IV . The patients receiving 600 mg Tegafur daily were then divided into two groups according to whether LMS was also given or not . LMS was administered for 3 days before the operation in a daily dose of 150 mg and for 1 year or more after operation according to a schedule of 3 days ' administration followed by an 11-day interval . The 2-year follow-up demonstrated that in stage III patients , the LMS ( + ) regimen was superior to the LMS ( − ) regimen , since the former prolonged the relapse-free interval significantly . The survival rate for stage III disease was also significantly higher in the LMS ( + ) than in the LMS ( − ) group . There was no significant difference in the incidence of subjective or objective side-effects between two groups . The incidence of agranulocytosis was comparable in the two groups", "This prospect i ve evaluation of 5‐fluorouracil ( 5‐FU ) and methyl‐CCNU administered in combination to patients with surgery for histologically proved gastric adenocarcinoma is based upon 312 patients r and omized between August 1974 and May 1980 . Patients were stratified into three categories of resectability , ( 1 ) complete , ( 2 ) proven incomplete , and ( 3 ) nonresectable , prior to r and om treatment assignment to surgery alone or surgery followed by adjuvant chemotherapy . Drug therapy consisted of discrete 5‐day courses administered at 7‐week intervals . Toxic reactions were reported in association with 42 % of the courses . Treatment was suspended or discontinued in 6 % of the courses because of hematologic toxicity . Treated patients with curative resections experienced a more favorable survival than did controls , but the early advantage was lost by the end of the second follow‐up year . However , no statistically significant improvements in survival or reductions in risks of recurrence were observed . Similar proportions of treated and control deaths were attributable to residual or recurrent disease", "After curative resection for gastric adenocarcinoma , 103 patients , all with positive nodes , were r and omised so that 48 received adjuvant chemotherapy of epidoxorubicin ( EPI ) 75 mg m-2 on day 1 , leucovorin ( LV ) 200 mg m-2 on days 1 - 3 and 5-fluorouracil ( 5-FU ) 450 mg m-2 on days 1 - 3 , every 21 days for 7 months , whereas the remaining 55 did not . During the first year of observation , 21 control patients ( 38 % ) and five treated patients had recurrences . After a follow-up period of 36 months , 12 of the treated patients ( 25 % ) and only seven controls ( 13 % ) were still alive . At that point , the median survival was 13.6 months for the 55 untreated patients and 20.4 months for the 48 treated patients , a significant difference . We found a survival advantage for patients treated with the EPI-LV-5-FU regimen and a consistent delay in the appearance of recurrent or metastatic cancer . Acute toxicity was mild and treatment was well accepted by all patients . There was no long-term toxicity or any cardiac toxicity . We conclude that this particular chemotherapy , administered shortly after gastric resection , improves survival rate in node-positive gastric cancer patients , even although final assessment of this particular adjuvant approach must await completion of the trial", "Summary The clinical effectiveness of immunotherapy with the cell wall skeleton of Bacillus Calmette-Guérin was assessed in a study involving 140 consecutive patients with gastric cancer , who were gastrectomized at a single institution from January 1976 through December 1978 . These patients were r and omized by an envelope method after operation and divided into three treatment groups : ‘ control ’ , ‘ chemotherapy ’ , and ‘ chemotherapy plus immunotherapy with BCG-CWS . ’ Only two patients who died during surgery were excluded , and a survey of survival periods was made on the remaining 138 patients in January 1982.As a result , statistically significant differences in the survival rate curve were observed between the control and chemotherapy plus immunotherapy groups ( P chemotherapy and chemotherapy plus immunotherapy groups ( P BCG-CWS as an adjuvant immunotherapeutic agent in gastrectomized cancer patients", "PURPOSE An attempt was made to define the role of radiotherapy before operation for AGC . METHODS AND MATERIAL S From January 1978 to May 1989 , a prospect i ve r and omized trial on preoperative radiotherapy ( R+S ) vs. surgery alone ( S ) for AGC was carried out in 370 patients . Patients were r and omized into a combined group ( R+S , 171 patients ) or a surgery alone group ( S , 199 patients ) by the envelope method . 8-MV photon or telecobalt was used for the preoperative radiation therapy , using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia , lower segment of the esophagus , fundus , lesser curvature , and hepatogastric ligament . Surgery was performed after 2 to 4 weeks rest . RESULTS The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10 % and 19.75 % , 20.26 % and 13.30 % , respectively . The survival curves of these two groups diverged right from the beginning after the operation over the ninth year . Statistics by Kaplan-Meier log rank test proves that the difference is significant ( chi2 = 6.74 , p = 0.0094 ) . The immediate results were : resection rate 89.5 % and 79.4 % ( p pathologic stage after resection T2 12.9 % and 4.5 % ( p lymph node metastasis rates 64.3 % and 84.9 % ( p operative mortality rates 0.6 % and 2.5 % ; intrathoracic leak rates 1.8 % and 4.0 % , respectively . The causes of failure were : local uncontrol and recurrence 38.6 % vs. 51.7 % ( p regional lymph node metastasis 38.6 % vs. 54.6 % ( p distant metastasis 24.3 % vs. 24.7 % . CONCLUSION Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia", "Gastric carcinoma is decreasing in incidence in Western Europe and the United States . However , this disease is still a major cause of cancer death [ 1 ] . Extended surgical procedures over the past 20 years have not profoundly altered the poor outcome of patients with gastric carcinoma [ 2 ] . This fact indicates that surgery alone may not be enough to control the disease . In 1978 we began a prospect i ve r and omized , one-center trial to determine , whether postoperative treatment with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) , and cytosine-arabinoside ( Ara-C ) given for three courses could substantially improve the overall survival of patients treated by curative resection for gastric carcinoma . The regimen employed had been shown to be the most effective chemotherapy combination at the time the study started [ 3 ] . At a median follow-up of 5 years we found no significant effect of adjuvant chemotherapy on overall survival compared with an untreated control group . However , in a retrospective subgroup analysis we observed a significant improvement in the overall survival of patients with the intestinal tumor type , but no effect in patients with mucocellular carcinoma . We therefore believe that there is a selective effect of adjuvant chemotherapy in patients with gastric carcinoma with intestinal type of tumors", "PURPOSE Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles ( M-CH ) in preventing intraabdominal recurrence following curative surgery for gastric cancer . The Austrian Working Group for Stomach Cancer , a subgroup of the Austrian Working Group for Surgical Oncology , initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen . PATIENTS AND METHODS A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were r and omly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound ( n = 46 ) or served as a surgical control group ( n = 45 ) . Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment . RESULTS After a median observation period of 597 days ( range , 72 to 1,096 ) , a significantly higher postoperative complication rate was observed in the M-CH group ( 35 % ) compared with the control group ( 16 % ) ( P mortality rate was also significantly elevated in the M-CH group ( 11 % v 2 % in the control group ) . Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy , the protocol committee decided to stop further recruitment of patients onto this study . CONCLUSION Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications . However , no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial", "Abstract Purpose : To evaluate FAM [ 5-FU ( 5-fluorouracil ) , doxorubicin , mitomycin C ] chemotherapy as adjuvant therapy for patients with resected TNM stage I , II , or III gastric carcinoma . Patients and Methods : One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles ( 1 year ) of postoperative FAM chemotherapy with observation only . Results : The median follow-up on this study was 9.5 years . For all patients , no differences ( log-rank analysis ) in disease-free survival ( p=0.45 ) and overall survival ( p=0.57 ) between FAM therapy ( 93 cases ) and surgery ( 100 cases ) were observed . Quality of surgical resection affected survival irrespective of FAM use . Cases with curative resection , defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm , had superior survival compared to cases not meeting these requirements ( p FAM was well tolerated with 6 % ( five of 90 ) of cases demonstrating grade IV hematologic toxicity . There were two drug-related fatalities ( one cardiomyopathy , one hematolytic uremic syndrome ) . Conclusion : FAM is not effective adjuvant therapy for TNM stage I , II , and III patients with resected gastric cancer . Future adjuvant studies must emphasize prospect i ve surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period", "In order to evaluate the clinical effectiveness of immunotherapy on gastric cancer patients , we performed two controlled trials of immunotherapy with BCG-CWS and Nocardia rubra CWS respectively . A controlled trial of BCG-CWS was performed from 1976 to 1978 . The result showed an improved survival rate of the immunotherapy as compared with the chemotherapy group . From September 1979 through March 1981 , a total of 302 patients with gastric cancer undergoing gastrectomy at the Department of Surgery , Chiba University Hospital and its 14 affiliated hospitals were studied for clinical effectiveness of immunotherapy with N-CWS . The subjects were stratified by a gross stage of cancer and degree of operative curability . They were then r and omly assigned to either chemotherapy group or chemotherapy plus immunotherapy group . Immunotherapy used was intradermal injection of 400 micrograms of N-CWS which was given weekly for the first month and monthly thereafter . After the specimen was examined microscopically , the patients were classified by histological stage of cancer and radicality of surgical intervention into curative or non-curative groups . The patients were surveyed for survival period in December 1981 . No statistical difference was found between the two treatment groups in age , sex or operative procedures that might influence the patient 's survival . As a result , statistical intergroup difference in survival rates was not seen in patients of the curative group , probably due to short observation period . However , the intergroup difference in survival rates was statistically significant in patients of the non-curative group ( p less than 0.01 ) . These results indicate that the immunotherapy with BCG-CWS or with N-CWS is effective in patients undergoing gastrectomy for gastric cancer", " A group of 243 patients with gastric cancer was subjected to a prospect i ve r and omized trial of adjuvant chemotherapy after curative gastrectomy . One of the three arms ( regimen A ) is induction therapy with a three-drug combination of mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) , and cytosine arabinoside ( ara-C ) followed by intermittent oral administration of 5-FU for two years ( MFC + F ) . In regimen B , 5-FU in regimen A is replaced by ftorafur , administered on the same schedule as regimen A ( MF'C + F ' ) . Regimen C is the control , in which patients are treated by surgery alone . Regimen A was proven effective for the suppression of relapse in the limited groups of moderately locally advanced cancer ; five-year survival rates of the subset of stages I , II , and III were 72.1 % with regimen A and 53.1 % with regimen C ( P less than .05 ) . Regimen B yielded a better survival than the control , although the difference did not reach statistical significance . The results seem to favor 5-FU as adjuvant chemotherapy for gastric cancer", "In a multicenter trial the efficacy of intraperitoneal administration of cisplatin after radical or palliative resection of gastric carcinoma with respect to overall survival was investigated . In 64 r and omised patients , patients treated with intraperitoneal perfusion did not show a benefit in the overall survival after a median follow-up of 18 months", "The effect of postoperative immunochemotherapy with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) and OK-432 was evaluated as an adjuvant therapy after curative resection for gastric cancer . Immediately after surgery , patients were r and omly allocated to the following three treatments : ( A ) chemotherapy with MMC and 5-FU ( 32 cases ) ; ( B ) chemoimmunotherapy with MMC , 5-FU and OK-432 ( 33 cases ) ; and ( C ) surgery alone as control ( 34 cases ) . There were no significant differences in the background factors influencing survival time among the groups , and there was no dose-distribution of chemotherapeutic agents between groups A and B. While the differences were not statistically significant , the survival rate and disease-free interval of group B were better than those of groups A or C. Side effects such as gastroenteric disorder , leukopenia ( less than 3,000/mm3 ) , thrombocytopenia ( less than 7 X 10(4)/mm3 ) and increase of serum transaminase level ( GPT greater than or equal to 100 units ) were less frequently observed in group B than in group A. The results of the present study seemed to indicate that chemoimmunotherapy with OK-432 may be effective for surgical adjuvant therapy", "Following curative resection for gastric adenocarcinoma , 142 patients were r and omized to receive adjuvant chemotherapy of methyl‐CCNU and 5‐FU or to be closely followed without chemotherapy . The median patient has been followed for four years . At the present time , there have been 38 recurrences and 40 deaths among the 71 patients in the control arm and 28 recurrences with 29 deaths in the group of patients r and omized to chemotherapy . Median survival for control patients is 33 months whereas it is estimated to be in excess of four years for the adjuvant therapy group . A survival advantage appears to be associated with adjuvant treatment , a test for treatment difference being significant ( P covariates . Survival and disease‐free intervals are longer in the chemotherapy arm for patients in all prospect i ve stratification subgroups ( proximal and total vs distal subtotal gastrectomy , presence or absence of lymph node metastases , invasion of adjacent organs vs confined to stomach wall and location of tumor within the stomach ) . A final assessment of this surgical adjuvant approach must await complete results of this trial , as well as of others currently in progress evaluating this same concept", "The aim of this trial was to investigate whether pre-operative chemotherapy leads to a 15 % higher curative resectability rate in patients with operable gastric cancer . In this r and omised trial , patients were allocated to receive either four courses of chemotherapy using 5-fluorouracil , doxorubicin and methotrexate ( FAMTX ) prior to surgery or to undergo surgery only . Patients younger than 75 years of age with a good physical and mental condition and a histologically proven adenocarcinoma of the stomach without clinical or radiographic ( computed tomography scan ) evidence of distant metastases were eligible for this trial . Early gastric cancer or cardia carcinoma were excluded . The response to chemotherapy was evaluated after two and four courses . In case of progressive disease ( PD ) after two courses , patients were operated upon as soon as possible . Otherwise complete response ( CR ) partial response ( PR ) or stable disease ( SD ) , two more courses were scheduled . The st and ard surgical procedure was a limited lymphadenectomy ( D1 ) with staging biopsy of the para-aortic lymph nodes . Between September 1993 and February 1996 , 56 eligible and evaluable patients were entered : 27 were r and omised to receive FAMTX before surgery and 29 to undergo surgery only . In the FAMTX + surgery treatment group , 15/27 ( 56 % ) had curative resections versus 18/29 ( 62 % ) in the surgery only arm . There was no difference in the frequency of TNM stages I + II in both treatment arms : 15/27 versus 15/29 . Due to PD and /or toxicity , 12 patients ( 44 % ) could not complete the planned four courses of FAMTX . Response evaluation after chemotherapy was possible in 25 patients : 2 CR , 6 PR , 8 SD and 9 PD . The difference in curative resectability rate was 6.5 % ( 95 % confidence interval -32 to + 19 % ) in favour of surgery only . Downstaging for stages I + II did not occur . PD was more often the reason for not completing the planned four courses than toxicity . More active regimens than FAMTX are required for future r and omised trials", "A study group including 55 institutions in Japan evaluated the effect of adjuvant cyclophosphamide therapy on 461 patients who had undergone curative resection for stomach cancer . Patients , who were followed up for over three years , were r and omly divided into three groups : curative resection and long-term drug therapy ; curative resection and short-term drug therapy ; and curative resection and no drug therapy . Long-term therapy consisted of ( a ) twice-weekly intravenous doses of 500 mg of cyclophosphamide for four weeks and , after five weeks with no medication , ( b ) 100 mg/day , given orally , for 40 days and , after ten weeks with no medication , ( c ) 100 mg/day , given orally , for 40 days . Short-term therapy consisted of only the first course of therapy ( ie , twice-weekly intravenous doses of 500 mg for four weeks ) . The effect of cyclophosphamide differed , depending on the patients ' levels of serosal and lymph node invasion : Short-term therapy was more effective in patients with lymph node involvement , and long-term therapy was more effective in patients with serosal involvement", "The overall survival in patients with gastric cancer is low , even among those undergoing resection . It has been hoped that the development of adjuvant therapy might improve survival in patients following surgery when tumour burden was minimal and both chemotherapy and radiotherapy have been proposed as suitable for use in gastric cancer . Their value has been evaluated by the British Stomach Cancer Group Second adjuvant therapy trial . 436 patients entered a prospect i ve , r and omised , controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy with mitomycin , doxorubicin , and fluorouracil after gastrectomy for adenocarcinoma . After at least 5 years , there have been 372 deaths of which 7 were due to surgical complications and 327 from recurrent cancer . Following stratified r and omisation , 145 patients were allocated to surgery alone , 153 to receive adjuvant radiotherapy , and 138 to adjuvant combination chemotherapy . The overall 2-year and 5-year survival were 33 % ( 95 % confidence interval 31 - 35 % ) and 17 % ( 13 - 21 % ) . No survival advantage has been shown for those patients receiving either adjuvant therapy compared to those undergoing surgery alone . The 5-year survival for surgery alone was 20 % , for surgery plus radiotherapy 12 % , and for surgery plus chemotherapy 19 % . Surgery , therefore , remains the st and ard treatment for this condition and the use of adjuvant treatments should be restricted to controlled trials", "A prospect i ve controlled study of combined chemotherapy with 5-fluorouracil , vinblastine and cyclophosphamide was conducted in 53 patients with radical resection for gastric carcinoma . The patients were divided into two groups , a control group of 26 patients and a chemotherapy group of 27 patients , that were similar in regard to age , sex , location of carcinoma , type of resection and pathologic findings . No significant differences in survival rate were observed between the control group and the chemotherapy groups", "In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma , we carried out a r and omized trial comparing surgery and surgery+adjuvant IORT . The study included 115 patients within a 74-month period , 51 of them received a single application of 28 Gy to the celiac axis . Patients were comparable with regard to age , sex , tumor stage and operative morbidity . The difference in mean survival time ( IORT : 26.9 months vs. non-IORT , 30.8 months ) and tumor-related death in the long-term course ( mean follow-up period 29.2 months ) with 29.4 % ( 15/51 ) in the IORT-treated patients vs. 31.2 % ( 20/64 ) in non-irradiated patients did not reach significance", "Three hundred fifteen patients with operable gastric cancer were r and omized to receive fluorouracil , Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) , and mitomycin ( FAM ) or no adjuvant treatment between September 1981 and July 1984 . After excluding ineligible patients , 281 patients are included in this analysis . Treatment was moderately well tolerated by the majority of patients , the common side effects being nausea and vomiting ( 58 % ) and alopecia ( 57 % ) . Three possible treatment-related deaths were seen , all due to cardiac failure . At median follow-up of 68 months , 164 patients have died , 73 in the treated arm and 91 in the control arm . There was no significant difference in disease-free or overall survival between the two arms of the study ( P = 0.21 ) . There is some evidence that patients with more advanced carcinoma ( T3-T4 ) derived some benefit from treatment ( P = 0.04 ) . The interpretation of this finding must take into account that all subgroups were defined retrospectively , and this could , therefore , be a chance finding . We conclude that adjuvant chemotherapy as given in this trial is not indicated as routine treatment in operable gastric cancer , but that further evaluation in stage T3-T4 patients is warranted", "One hundred-three patients with a potentially curative operation of a histologically proven gastric cancer were r and omly assigned to a control and chemotherapy group after stratification according to tumor stage II and III . Chemotherapy courses with 5-fluorouracil ( 10 mg/kg/day ) and BCNU ( 40 mg/m2/day ) for 5 days were administered eight times in 6 - 8 week intervals . Age , sex , and tumor location were matched in the chemotherapy and control groups . Five patients declined treatment after r and omization . Three years after initiating the study , the tumor has recurred in 38 of the 103 patients . There were 21 recurrences of 54 controls and 14 recurrences of 44 patients who received chemotherapy , and 17 and ten deaths , respectively , due to tumor relapse . The results of our study to data show a high degree of statistical probability that adjuvant chemotherapy with the regime used has no influence on the recurrence-free interval and survival time in gastric cancer", "BACKGROUND / AIMS Gastric cancer remains a disease with a poor and dismal prognosis even after radical surgical resection . The present study attempts to clarify whether neo and adjuvant hypoxic upper abdominal chemotherapy can improve the survival of patients with gastric cancer undergoing radical surgical resection . Patterns of failure after surgery for gastric cancer include peritoneal seeding , resection margin recurrence , and liver metastasis . METHODOLOGY From October 1995 to February 1999 , 58 patients with resectable gastric cancer were r and omly assigned to three groups . Hypoxic upper abdominal chemotherapy was carried out using Mitomycin-C , 5-Fluorouracil , Leucovorin , and Farmorubicin , 10 days before surgery , and 20 days following surgery , in Group A ( n=20 ) with or without in Group B ( n=19 ) systemic chemotherapy ; the remaining patients ( Group C : n=19 ) had neither neo nor adjuvant treatment . RESULTS The 4-year survival of Group C patients was 29.2 % . Group A patients ( surgery plus hypoxic neo and adjuvant chemotherapy and systemic chemotherapy ) had a 4-year survival of 45.5 % versus a 4-year survival of 39.2 % of Group B patients ( surgery and hypoxic neo and adjuvant abdominal perfusion ) . Patients of all stages , histologically confirmed , were included in this study . CONCLUSIONS Patients suffering from gastric carcinoma have demonstrated statistically improved survival by combining resectional surgery with neo and adjuvant hypoxic upper abdominal perfusion and adjuvant systemic chemotherapy", "This study evaluated combined 5‐fluorouracil ( 5FU ) and doxorubicin as postoperative adjuvant chemotherapy for patients who had undergone potentially curative resection of a primary gastric adenocarcinoma . One hundred twenty‐five eligible and evaluable patients were stratified according to extent of surgical resection , location of the primary tumor within the stomach , and lymph node status . They were then r and omized to either receive three cycles of chemotherapy or be observed . The median time from patient entry was 7 years . Results showed no significant difference in time to recurrence . The 5‐year survival rate was 33 % for the observation arm and 32 % for the adjuvant therapy arm . The data excluded a 16 % improvement in the 5‐year survival rate for patients receiving chemotherapy with a P value less than 0.05 . There were two drug‐related fatalities due to sepsis . These results demonstrate no substantive benefit for this chemotherapy regimen as postoperative adjuvant treatment of resected gastric cancer", "PURPOSE The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor , predominantly due to metastatic spread of the tumor . Depending on the type of tumor histology , the pathway of metastases is mainly peritoneal or hepatic dissemination . Interruption of this mechanism may be possible by intraperitoneal chemotherapy ( IPT ) . PATIENTS AND METHODS In a prospect i ve r and omized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer , 33 patients underwent adjuvant postoperative IPT with cisplatin , while 34 control subjects remained untreated . RESULTS Patients in the treatment group received a median of four IPT perfusions . Apart from frequent nausea , no adverse reactions or complications were noted . The median disease-free survival duration s were 12.7 months and 9.7 months in treated patients and controls , respectively ( P = .8 ) . After a median follow-up duration of 72 months , 54 patients ( 80 % ) had died of primary disease or related complications . The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls ( P = .6 ) . Autopsies were performed on 12 ( 18 % ) of 54 patients who died , and showed tumor spread to the peritoneal cavity and /or to the liver , irrespective of the application of IPT . CONCLUSION IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer . The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent , an inefficient modus of application , or a lack of sufficient drug penetration into the serosa or peritoneal metastasis", "Background . Continuous hyperthermic peritoneal perfusion ( CHPP ) with a solution that contained 10 μg/ml mitomycin C was devised initially as a method for intraperitoneal thermochemotherapy . The authors conducted a r and omized clinical trial to evaluate the efficacy of CHPP as a prophylactic treatment for prevention of peritoneal recurrence of gastric cancer with serosal invasion", " A group of 496 cases was used in a controlled trial to study the possible value of mitomycin C as an adjuvant to curative surgery for gastric cancer . Patients assigned to receive the drug were given mitomycin C , 0.8 mg/kg body weight intravenously , twice a week for 5 weeks immediately after surgery . The control group was treated with surgery alone . Sixty-six patients were excluded from the study because of non-curative surgery . There was no over-all difference in survival and cancer death rates at 5 and 10 years between treated and control groups . However , a survival rate 18.6 % higher at 5 years was observed in the subset of patients who had moderately advanced lymphatic metastases , and a survival rate 26.4 % higher at 5 years was observed in the subset of patients who had involved serosa . The difference in cancer death rate was 14.5 and 24.0 % in each subset , respectively . These significant differences persisted at 10 years . The effect of chemotherapy seemed to result from the successful inhibition of peritoneal dissemination and local recurrence . An adverse effect was observed in patients in the early stages cancer . These results suggest that mitomycin C could be useful as an adjuvant to curative surgery for moderately advanced stages of gastric cancer ", "The results of a prospect i ve r and omized trial of adjuvant treatment after curative resection for gastric cancer are reported . The study consisted of three arms : ( 1 ) surgery only ; ( 2 ) chemotherapy ( 5‐fluoro‐uracil ( FU ) and 1‐(2‐chloroethyl)‐3‐(4‐methylcyclohexil)‐1‐nitrosourea ( Me‐CCNU ) ) after surgery ; ( 3 ) chemo‐immunotherapy ( FU , Me‐CCNU and levamisole ) after surgery . Between March 1977 and June 1981 , 235 patients were included in the study by 18 co‐operating institutions . Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity , necessitating interruption of treatment . Two of these patients died of marrow aplasia . Statistical analysis of survival showed that prognosis was influenced by the well‐known prognostic variables , invasion of the wall , nodal status and site of tumour . The different treatments in the three arms , however , did not show any impact on prognosis , even when adjustments were made for the most relevant prognostic variables . Given the lack of effect on survival and the presence of clinical ly important toxicity , FU and Me‐CCNU ± levamisole can not be recommended as adjuvant therapy for resected gastric cancer", "BACKGROUND To study the survival benefit of adjuvant chemotherapy in gastric cancer , seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer . METHODS 579 patients were enrolled in the study , stratified by disease stage ( T1 , n=188 ; T2 , n=323 ) , and allocated r and omly adjuvant chemotherapy or no further treatment . 285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible . Six cases were excluded because they did not fulfill the entry criteria . The treatment group had intravenous mitomycin ( 1.4 mg/m2 ) and fluorouracil ( 166.7 mg/m2 ) twice weekly for 3 weeks after surgery , and oral UFT ( uracil plus tegafur , 300 mg daily ) for 18 months . Analyses were by intention to treat . FINDINGS No serious toxic effects were observed in the treatment group . At median follow-up of 72 months , 59 patients in the control group and 47 in the treatment group had died . There was no significant difference in survival between the groups ( 5-year survival 82.9 % control vs 85.8 % treated ; hazard ratio 0.738 [ 95 % CI 0.498 - 1.093 ] ) . 5-year survival of patients with T1 ( mucosal or submucosal ) cancer in the control and treatment groups was 94.9 % versus 92.0 % , and that of patients with T2 ( muscularis propria or subserosa ) cancer was 76.9 % versus 83.0 % . However , a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response . INTERPRETATION There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer ( T1 and T2 ) after curative gastrectomy . Patients with T1 cancer can be excluded from future trials , because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy", "As a result of their previous experience with mitomycin C at high discontinuous doses in advanced gastric cancer , the authors studied its role as an adjuvant for locally advanced cases after surgical complete resection . Results from 70 evaluable patients are presented . Patients were allocated r and omly to receive mitomycin C , 20 mg/m2 I.V. direct once every 6 weeks , four courses , or a placebo . After a follow-up period of 250 weeks , seven patients of treatment arm and 23 controls have already relapsed ( p Toxicity was moderate and controllable by symptomatic measures . The authors consider this investigation a positive contribution in the field of adjuvant therapy of gastric cancer", "A cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer was carried out by Kondo 's group from July 1974 to December 1977 . A total of 848 patients with gastric cancer underwent curative resection were eligible . Of 848 patients , 819 cases with complete description of patient 's background were evaluable : Group A ( surgery + MMC + 5-FU : chemotherapy ) 253 cases , group B ( surgery + MMC + 5-FU + OK-432 or PSK : immunochemotherapy ) 282 and group C ( surgery alone ) 284 . The 5-year corrected survival rates of total cases using Cox 's proportional hazard model were 76.2 % with group A , 73.6 % with group B and 73.3 % with group C. And the 10-year survival rates were 67.6 % with group A , 64.3 % with group B and 63.9 % with group C. The difference in survival rate among groups A , B and C was not statistically significant . In the evaluation of prognostic factors by Cox 's proportional hazard model , level of curative resection , extent of resection , histological stage and Kajitani 's classification had an influence upon survival rates , in which degrees of metastasis in lymph node and serous infiltration were also involved . The significance of postoperative adjuvant immunochemotherapy has not been clarified", "PURPOSE In a r and omized clinical trial ( European Organization for the Research and Treatment of Cancer [ EORTC ] no. 40813 ) on adjuvant chemotherapy in gastric cancer , results obtained after administration of the FAM2 regimen ( fluorouracil [ 5-FU ] , doxorubicin , and mitomycin ) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival , time to progression , and disease-free interval . PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III ( International Union Against Cancer [ UICC ] 1978 ) gastric adenocarcinoma were r and omized to receive chemotherapy ( treatment arm ) or no further treatment ( control arm ) . The chemotherapy schedule was repeated every 43 days for seven cycles . The log-rank test and the Cox model were used for statistical analysis . RESULTS Of 314 patients , 159 comprised the control group and 155 the FAM2 group . Nineteen FAM2 patients never received chemotherapy . The median number of cycles was five . Of the patients started on adjuvant treatment , severe hematologic and nonhematologic toxicity ( grade s 3 or 4 , World Health Organization [ WHO ] scale ) occurred , respectively , in 6 % to 9 % and in 1 % to 29 % of cases . The overall 5-year survival rate was 70 % for stage II and 32 % for stage III patients . No statistically significant difference was found between overall survival of the two treatment arms ( P = .295 ) . However , time to progression was significantly delayed in the FAM2 arm ( P = .020 ) and disease-free survival showed borderline significance ( P = .068 ) . CONCLUSION FAM2 , in view of its high toxicity , can not be advocated as st and ard adjuvant treatment for gastric cancer . Large-scale clinical trials using more active , less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit", "PURPOSE The efficacy of adjuvant chemotherapy in gastric cancer is controversial . We conducted a phase III , r and omized , multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer . PATIENTS AND METHODS Patients with resected stage III gastric adenocarcinoma were r and omly assigned , using sealed envelopes , to receive either chemotherapy or no further treatment . Chemotherapy was started within 28 days after surgery according to the following schedule : mitomycin 20 mg/m(2 ) intravenously ( bolus ) at day 1 of chemotherapy ; 30 days later , oral tegafur at 400 mg bid daily for 3 months . Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model . RESULTS Between January 1988 and September 1994 , 148 patients from 10 hospitals in Catalonia , Spain , were included in the study . The median follow-up period was 37 months . The tolerability of the treatment was excellent . The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy ( P = .04 for survival and P = .01 for disease-free survival in the log-rank test ) . The overall 5-year survival rate and the 5-year disease-free survival rate were , respectively , 56 % and 51 % in the treatment group and 36 % and 31 % in the control group . CONCLUSION Our positive results are consistent with the results of recent studies ; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer", " 411 patients were entered into a prospect i ve , r and omised controlled trial of adjuvant chemotherapy after gastrectomy for adenocarcinoma . After a follow-up of at least 5 1/2 years there has been no survival advantage for those receiving adjuvant 5-fluorouracil and mitomycin C with or without an induction course of 5-fluorouracil , vincristine , cyclophosphamide , and methotrexate compared with those undergoing surgery only . There have been 366 deaths , including 22 from treatment-related conditions . A multivariate analysis of prognostic factors demonstrated that stage of disease , nodal and resection margin involvement , and the presence of residual disease are significant determinants of survival . Weight loss before surgery had a significant independent influence on survival . The combination of preoperative symptoms and intraoperative findings may be used to select patients for radical or palliative procedures", "Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful , largely because the drugs are not retained in the peritoneal cavity . We have assessed the prophylactic efficacy of a delayed-release preparation -- mitomycin adsorbed onto activated charcoal ( M-CH ) . 50 patients with gastric cancer and serosal infiltration were r and omly assigned intraperitoneal treatment with M-CH ( 50 mg mitomycin intraoperatively ) or no anticancer prophylaxis ( control ) . Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients ( 1 was lost to follow-up ) than among the 25 controls ( p less than 0.01 ) . There were significant differences in survival between the groups at 1.5 years after r and omisation ( difference 34.6 % [ 95 % confidence interval 8.5 - 60.8 % ] ; p less than 0.01 ) and at 2.0 , 2.5 , and 3.0 years ( 41.7 % [ 14.2 - 69.1 % ] ; p less than 0.005 ) . The concentration of mitomycin was significantly higher in peritoneal exu date than in plasma for 24 h after drug administration . Side-effects were slight and well tolerated . Thus , peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer , presumably by a prophylactic effect on peritoneal recurrence", "BACKGROUND The extent to which chemotherapy may relieve tumour-related symptoms , improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality . The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients . PATIENTS AND METHODS Between January 1991 and February 1995 , 61 patients with gastric cancer were r and omized to either chemotherapy in addition to best supportive care or to best supportive care . Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation . Chemotherapy was the ELF-regimen consisting of 5-fluorouracil , leucovorin and etoposide , or , in elderly patients with poor performance , a 5-fluorouracil/leucovorin regimen ( FLv ) . Quality of life was evaluated with the EORTC-QLQ-C30 instrument . RESULTS More patients in the chemotherapy group ( 45 % , 14/31 ) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group ( 20 % , 6/30 , P Overall survival was longer in the chemotherapy group ( median 8 vs. 5 months ) although the difference was not statistically significant ( P = 0.12 ) . After corrections for imbalances in pretreatment characteristics , chemotherapy treatment was , however , associated with a survival benefit ( P = 0.003 ) . Also , the quality -adjusted survival time and time to disease progression were longer for patients r and omized to chemotherapy ( median 5 vs. 2 months , P = 0.03 ) . CONCLUSIONS The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer . The number of patients who benefit from treatment is , however , still rather limited" ]	41184faa-06ff-11f0-808a-c43d1ab1c353
Importance There is growing evidence that vitamin D plays a role in the pathogenesis of asthma but it is unclear whether supplementation during childhood may improve asthma outcomes . Objectives The objective of this systematic review and meta- analysis was to evaluate the efficacy and safety of vitamin D supplementation as a treatment or adjunct treatment for asthma . Data Sources We search ed MEDLINE , Embase , CENTRAL , and CINAHL through July 2014 . Study Selection We included RCTs that evaluated vitamin D supplementation in children versus active control or placebo for asthma . Data Extraction and Synthesis One review er extracted data and one review er verified data accuracy . We qualitatively summarized the main results of efficacy and safety and meta-analyzed data on comparable outcomes across studies . We used GRADE for strength of evidence . Main Outcome Measures Main planned outcomes measures were ED visits and hospitalizations . As secondary outcomes , we examined measures of asthma control , including frequency of asthma exacerbations , asthma symptom scores , measures of lung function , β2-agonist use and daily steroid use , adverse events and 25-hydroxyvitamin D levels . Results Eight RCTs ( one parallel , one crossover design ) comprising 573 children aged 3 to 18 years were included . One study ( moderate- quality , n = 100 ) reported significantly less ED visits for children treated with vitamin D. No other studies examined the primary outcome ( ED visits and hospitalizations ) . There was a reduced risk of asthma exacerbations in children receiving vitamin D ( low- quality ; RR 0.41 , 95 % CI 0.27 to 0.63 , 3 studies , n = 378 ) . There was no significant effect for asthma symptom scores and lung function . The serum 25(OH)D level was higher in the vitamin D group at the end of the intervention ( low- quality ; MD 19.66 nmol/L , 95 % CI 5.96 nmol/L to 33.37 nmol/L , 5 studies , n = 167 ) . Limitations We identified a high degree of clinical diversity ( interventions and outcomes ) and method ological heterogeneity ( sample size and risk of bias ) in included trials . Conclusions and Relevance R and omized controlled trials provide some low- quality evidence to support vitamin D supplementation for the reduction of asthma exacerbations . Evidence on the benefits of vitamin D supplementation for other asthma-related outcomes in children is either limited or inconclusive . We recommend that future trials focus on patient-relevant outcomes that are comparable across studies , including st and ardized definitions of asthma exacerbations	[ "OBJECTIVE : Observational studies suggest that serum levels of 25-hydroxyvitamin D ( 25[OH]D ) are inversely associated with acute respiratory infections ( ARIs ) . We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs . METHODS : By using cluster r and omization , classrooms of 744 Mongolian schoolchildren were r and omly assigned to different treatments in winter ( January – March ) . This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk ( control ; n = 104 ) or milk fortified with 300 IU of vitamin D3 ( n = 143 ) . This comparison was double-blinded . The primary outcome was the number of parent-reported ARIs over the past 3 months . RESULTS : At baseline , the median serum 25(OH)D level was 7 ng/mL ( interquartile range : 5–10 ng/mL ) . At the end of the trial , follow-up was 99 % ( n = 244 ) , and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different ( 7 vs 19 ng/mL ; P receiving vitamin D reported significantly fewer ARIs during the study period ( mean : 0.80 vs 0.45 ; P = .047 ) , with a rate ratio of 0.52 ( 95 % confidence interval : 0.31–0.89 ) . Adjusting for age , gender , and history of wheezing , vitamin D continued to halve the risk of ARI ( rate ratio : 0.50 [ 95 % confidence interval : 0.28–0.88 ] ) . Similar results were found among children either below or above the median 25(OH)D level at baseline ( rate ratio : 0.41 vs 0.57 ; Pinteraction = .27 ) . CONCLUSIONS : Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency", "BACKGROUND Asthma exacerbations , most often caused by respiratory tract infections , are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs . Vitamin D status might play a role in preventing asthma exacerbations . OBJECTIVES We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations . METHODS We measured 25-hydroxyvitamin D levels in sera collected from 1024 children with mild-to-moderate persistent asthma at the time of enrollment in a multicenter clinical trial of children r and omized to receive budesonide , nedocromil , or placebo ( as-needed beta-agonists ) : the Childhood Asthma Management Program . Using multivariable modeling , we examined the relationship between baseline vitamin D levels and the odds of any hospitalization or emergency department visit over the 4 years of the trial . RESULTS Thirty-five percent of all subjects were vitamin D insufficient , as defined by a level of 30 ng/mL or less 25-hydroxyvitamin D. Mean vitamin D levels were lowest in African American subjects and highest in white subjects . After adjusting for age , sex , body mass index , income , and treatment group , insufficient vitamin D status was associated with a higher odds of any hospitalization or emergency department visit ( odds ratio , 1.5 ; 95 % CI , 1.1 - 1.9 ; P = .01 ) . CONCLUSION Vitamin D insufficiency is common in this population of North American children with mild-to-moderate persistent asthma and is associated with higher odds of severe exacerbation over a 4-year period", "BACKGROUND To our knowledge , no rigorously design ed clinical trials have evaluated the relation between vitamin D and physician-diagnosed seasonal influenza . OBJECTIVE We investigated the effect of vitamin D supplements on the incidence of seasonal influenza A in schoolchildren . DESIGN From December 2008 through March 2009 , we conducted a r and omized , double-blind , placebo-controlled trial comparing vitamin D(3 ) supplements ( 1200 IU/d ) with placebo in schoolchildren . The primary outcome was the incidence of influenza A , diagnosed with influenza antigen testing with a nasopharyngeal swab specimen . RESULTS Influenza A occurred in 18 of 167 ( 10.8 % ) children in the vitamin D(3 ) group compared with 31 of 167 ( 18.6 % ) children in the placebo group [ relative risk ( RR ) , 0.58 ; 95 % CI : 0.34 , 0.99 ; P = 0.04 ] . The reduction in influenza A was more prominent in children who had not been taking other vitamin D supplements ( RR : 0.36 ; 95 % CI : 0.17 , 0.79 ; P = 0.006 ) and who started nursery school after age 3 y ( RR : 0.36 ; 95 % CI : 0.17 , 0.78 ; P = 0.005 ) . In children with a previous diagnosis of asthma , asthma attacks as a secondary outcome occurred in 2 children receiving vitamin D(3 ) compared with 12 children receiving placebo ( RR : 0.17 ; 95 % CI : 0.04 , 0.73 ; P = 0.006 ) . CONCLUSION This study suggests that vitamin D(3 ) supplementation during the winter may reduce the incidence of influenza A , especially in specific subgroups of schoolchildren . This trial was registered at https://center.umin.ac.jp as UMIN000001373", "In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias", "BACKGROUND Decreased 25-hydroxyvitamin D [ 25(OH)D ] concentrations have been associated with an increased prevalence and severity of asthma and a lower response to inhaled corticosteroids . OBJECTIVE The objective was to determine the association between serum 25(OH)D concentrations and asthma prevalence , severity , and response to asthma treatment . DESIGN Secondary analyses were conducted in 2 sample s of adolescents 12 - 20 y of age : 1 ) NHANES 2001 - 2006 ( n = 6487 ) , a cross-sectional nationally representative sample of the US population , and 2 ) a cohort of inner-city adolescents with asthma managed prospect ively for 46 wk with guidelines -based therapy in the Asthma Control Evaluation ( ACE ; n = 226 ) trial . RESULTS Mean ( ±SD ) serum 25(OH)D concentrations in the NHANES and ACE sample s were lower in African Americans than in non-African Americans ( NHANES : 14.9 ± 6.5 compared with 23.0 ± 8.4 ng/mL , P , mean concentrations did not differ between participants without and with asthma ( African Americans : 14.9 ± 6.4 compared with 15.0 ± 6.6 ng/mL , respectively , P = 0.87 ; non-African Americans : 23.0 ± 8.5 compared with 23.6 ± 8.2 ng/mL , respectively , P = 0.16 ) . In the ACE models that used either a predefined cutoff ( regression , 25(OH)D concentrations showed either no relation or minor contradictory correlations with indicators of asthma severity , treatment requirements , spirometry , or atopy/inflammation . CONCLUSION In 2 sample s of adolescents , overall serum 25(OH)D concentrations were low and were not consistently associated with the presence of asthma , multiple asthma characteristics , asthma morbidity , or response to treatment . The ACE trial was registered at clinical trials.gov as NCT0011441", "Our objective was to assess whether administration of 25-OH-vitamin D to children with asthma treated with inhaled dry-powder budesonide 400 microg daily affects short-term growth or markers of bone turnover . We utilized a r and omized , double-blind , two-period crossover trial with run-in and washout periods of 2 weeks and treatment periods of 4 weeks duration . The setting was an Outpatient clinic in a secondary referral center . Subjects included 14 boys and 3 girls with a mean age of 11.7 ( range , 6.1 - 14.4 ) years . Interventions included 15 microg ( 600 IU ) 25-OH-vitamin D ( cholecalciferol ) in one tablet ABCDin(R ) once daily in the morning . Primary outcome measures were : lower leg growth rate , serum osteocalcin , and serum markers of type I collagen turnover , i.e. , the amino terminal propeptide of type I procollagen ( PINP ) , the carboxy terminal propeptide of type I procollagen ( PICP ) ( formation markers ) , and the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen ( ICTP ) ( degradation markers ) . Secondary outcome measures were parameters of asthma control and serum 25-OH-vitamin D. Lower leg growth rate was 0.22 mm/week during vitamin D and 0.25 mm/week during placebo treatment ( NS ) . Osteocalcin was 59.9 and 57.8 microg/l during vitamin D and placebo treatment , respectively , PINP 574 and 565 microg/l , PICP 381 and 382 microg/l , and ICTP 11.5 and 11.1 microg/l , respectively ( NS ) . Serum 25-OH-vitamin D was 76.3 nmol/l and 48.2 nmol/l , respectively ( P measures of pulmonary function . In conclusion , administration of 25-OH-vitamin D does not affect short-term growth or markers of bone turnover in children with asthma treated with inhaled dry-powder budesonide 400 microg daily", "Objective To define the therapeutic role of vitamin D in children with moderate to severe bronchial asthma as an adjunct to st and ard treatment . Methods Hundred asthmatic children of either sex , attending the respiratory and asthma clinic were enroled in the study . Diagnosis was made on the basis of history and clinical examination . R and omization was done using sealed opaque envelop method . In addition to the treatment as per GINA guidelines , one group received oral vitamin D3 ( Cholecalciferol ) 60,000 IU per month for 6 mo and the other group received placebo powder in the form of glucose sachet with a double blinded design . Monthly follow up of every patient was done and during every visit change in severity , level of control , Peak expiratory flow rate ( PEFR ) , steroid dosage , number of exacerbations and number of emergency visits were assessed . Results Monthly doses of 60,000 IU vitamin D significantly reduced the number of exacerbations as compared to placebo ( p = 0.011 ) . PEFR significantly increased in the treatment group ( p = 0.000 ) . Monthly doses of vitamin D significantly reduced the requirement of steroids ( p = 0.013 ) and emergency visits ( p = 0.015 ) . Control of asthma was achieved earlier in patients who received monthly vitamin D. Vitamin D significantly reduced the level of severity of asthma patients over 6 mo of treatment ( p = 0.016 ) . Conclusions Vitamin D has a definite role in the management of moderate to severe persistent bronchial asthma as an adjunct to st and ard treatment", "In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted", "This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence", "IMPORTANCE In asthma and other diseases , vitamin D insufficiency is associated with adverse outcomes . It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency . OBJECTIVE To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels . DESIGN , SETTING , AND PARTICIPANTS The VIDA ( Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma ) r and omized , double-blind , parallel , placebo-controlled trial study ing adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by January 2014 . After a run-in period that included treatment with an inhaled corticosteroid , 408 patients were r and omized . INTERVENTIONS Oral vitamin D3 ( 100,000 IU once , then 4000 IU/d for 28 weeks ; n = 201 ) or placebo ( n = 207 ) was added to inhaled ciclesonide ( 320 µg/d ) . If asthma control was achieved after 12 weeks , ciclesonide was tapered to 160 µg/d for 8 weeks , then to 80 µg/d for 8 weeks if asthma control was maintained . MAIN OUTCOMES AND MEASURES The primary outcome was time to first asthma treatment failure ( a composite outcome of decline in lung function and increases in use of β-agonists , systemic corticosteroids , and health care ) . RESULTS Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks ( 28 % [ 95 % CI , 21%-34 % ] with vitamin D3 vs 29 % [ 95 % CI , 23%-35 % ] with placebo ; adjusted hazard ratio , 0.9 [ 95 % CI , 0.6 - 1.3 ] ) . Of 14 prespecified secondary outcomes , 9 were analyzed , including asthma exacerbation ; of those 9 , the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control ( 111.3 µg/d [ 95 % CI , 102.2 - 120.4 µg/d ] in the vitamin D3 group vs 126.2 µg/d [ 95 % CI , 117.2 - 135.3 µg/d ] in the placebo group ; difference of 14.9 µg/d [ 95 % CI , 2.1 - 27.7 µg/d ] ) . CONCLUSIONS AND RELEVANCE Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency . These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01248065", "RATIONALE Low vitamin D levels are associated with asthma and decreased airway responsiveness . Treatment with inhaled corticosteroids improves airway responsiveness and asthma control . OBJECTIVES To assess the effect of vitamin D levels on prebronchodilator FEV(1 ) , bronchodilator response , and responsiveness to methacholine ( PC(20 ) , provocative concentration of methacholine producing a 20 % decline in FEV(1 ) ) in patients with asthma treated with inhaled corticosteroids . METHODS We measured 25-hydroxyvitamin D levels in the serum of children with persistent asthma at the time of enrollment in the Childhood Asthma Management Program . We divided subjects into the vitamin D sufficiency ( > 30 ng/ml ) , insufficiency ( 20 - 30 ng/ml ) , and deficiency ( change in prebronchodilator FEV(1 ) , bronchodilator response , and PC(20 ) from enrollment to 8 - 12 months . MEASUREMENTS AND MAIN RESULTS Of the 1,024 subjects , 663 ( 65 % ) were vitamin D sufficient , 260 ( 25 % ) were insufficient , and 101 ( 10 % ) were deficient . Vitamin D-deficient subjects were more likely to be older , African American , and have a higher body mass index compared with the vitamin D-sufficient and insufficient subjects . In the inhaled corticosteroid treatment group , prebronchodilator FEV(1 ) increased from r and omization to 12 months by 140 ml in the vitamin D-deficient group and prebronchodilator FEV(1 ) increased by 330 ml in the vitamin D insufficiency group and by 290 ml in the vitamin D sufficiency group ( P = 0.0072 ) , in adjusted models . CONCLUSIONS In children with asthma treated with inhaled corticosteroids , vitamin D deficiency is associated with poorer lung function than in children with vitamin D insufficiency or sufficiency", "BACKGROUND Research suggests an influence of micronutrients on childhood asthma . So far , evidence mainly originates from cross-sectional studies using nutrient intake data , which is not an accurate measure of nutrient status . This study aim ed to investigate the cross-sectional and prospect i ve associations between serum concentrations of magnesium , vitamin D , selenium , and zinc and prevalence of ( severe ) asthma , atopy , and bronchial hyperresponsiveness ( BHR ) in childhood . METHODS In the Prevention and Incidence of Asthma and Mite Allergy birth cohort study , serum nutrient concentrations were available for a 4-yr-old subgroup ( n = 372 ) and for a different 8-yr-old subgroup ( n = 328 ) . Yearly question naires inquired about asthma prevalence until 8 yr of age . Allergic sensitization was measured at 4 and 8 yr of age ; BHR was measured at 8 yr of age . Data were analyzed with logistic regression and generalized estimating equations models . RESULTS There was a consistent ( non-significant ) inverse association between serum magnesium concentrations and asthma prevalence . Serum vitamin D concentrations measured at age 4 were inversely associated with asthma at ages 4 - 8 [ e.g. , cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma : odds ratio ( OR ) : 0.49 , 95 % confidence interval ( CI ) : 0.25 - 0.95 ] , whereas vitamin D measured at age 8 was positively associated with asthma at age 8 ( e.g. , cross-sectional association between vitamin D tertile 3 vs. 1 and severe asthma : OR : 2.14 , 95 % CI : 0.67 - 6.82 ) . CONCLUSIONS Our study contributes to the evidence that children with higher serum magnesium concentrations are less likely to have asthma . The associations between serum vitamin D concentrations and asthma were age-dependent", "BACKGROUND Higher serum total 25-hydroxyvitamin D ( 25(OH)D ) concentrations have been associated with better lung function and lower risk of allergic disease . 25(OH)D3 constitutes the majority of total 25(OH)D and has been suggested to be more potent than 25(OH)D2 . We studied the prospect i ve associations of 25(OH)D2 and 25(OH)D3 with asthma , wheezing , flexural dermatitis , and lung function in children who participated in the Avon Longitudinal Study of Parents and Children-a population -based contemporary birth cohort of children born in 1991 - 1992 from South West Engl and . METHODS Serum 25(OH)D2 and 25(OH)D3 concentrations , measured at a mean age of 9.8 years , were related to incident cases of wheezing ( study sample : n = 3,323 , 141 cases ; 4 % ) , asthma ( n = 3,323 , 464 cases ; 14 % ) , and flexural dermatitis ( n = 3,748 , 300 cases ; 8 % ) , as well as lung function ( forced expiratory volume in 1 second [ FEV1 ] , forced vital capacity [ FVC ] , and mid-forced expiratory flow assessed at a mean age of 15.5 years : n = 2,259 ) . RESULTS 25(OH)D2 was inversely associated with flexural dermatitis ( adjusted odds ratio per doubling of exposure = 0.83 [ 95 % confidence interval = 0.72 - 0.94 ] ) and wheezing ( 0.83 [ 0.68 - 1.00 ] ) , and 25(OH)D3 was positively associated with flexural dermatitis ( 1.09 [ 1.00 - 1.18 ] ) and wheezing ( 1.14 [ 1.03 - 1.28 ] ) . 25(OH)D2 was weakly positively associated with FEV1 , and FVC . 25(OH)D3 was not associated with lung function . CONCLUSIONS These results suggest that higher 25(OH)D3 concentrations are associated with increased risk of wheezing and flexural dermatitis . Despite being one of the few prospect i ve studies and being able to adjust for confounders , these findings need replication . Our results do not provide strong evidence that lower concentrations of vitamin D are detrimental to respiratory and allergic health in children" ]	4118502c-06ff-11f0-808a-c43d1ab1c353
Importance The human and financial costs of treating surgical site infections ( SSIs ) are increasing . The number of surgical procedures performed in the United States continues to rise , and surgical patients are initially seen with increasingly complex comorbidities . It is estimated that approximately half of SSIs are deemed preventable using evidence -based strategies . Objective To provide new and up date d evidence -based recommendations for the prevention of SSI . Evidence Review A targeted systematic review of the literature was conducted in MEDLINE , EMBASE , CINAHL , and the Cochrane Library from 1998 through April 2014 . A modified Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) approach was used to assess the quality of evidence and the strength of the result ing recommendation and to provide explicit links between them . Of 5759 titles and abstract s screened , 896 underwent full-text review by 2 independent review ers . After exclusions , 170 studies were extracted into evidence tables , appraised , and synthesized . Findings Before surgery , patients should shower or bathe ( full body ) with soap ( antimicrobial or nonantimicrobial ) or an antiseptic agent on at least the night before the operative day . Antimicrobial prophylaxis should be administered only when indicated based on published clinical practice guidelines and timed such that a bactericidal concentration of the agents is established in the serum and tissues when the incision is made . In cesarean section procedures , antimicrobial prophylaxis should be administered before skin incision . Skin preparation in the operating room should be performed using an alcohol-based agent unless contraindicated . For clean and clean-contaminated procedures , additional prophylactic antimicrobial agent doses should not be administered after the surgical incision is closed in the operating room , even in the presence of a drain . Topical antimicrobial agents should not be applied to the surgical incision . During surgery , glycemic control should be implemented using blood glucose target levels less than 200 mg/dL , and normothermia should be maintained in all patients . Increased fraction of inspired oxygen should be administered during surgery and after extubation in the immediate postoperative period for patients with normal pulmonary function undergoing general anesthesia with endotracheal intubation . Transfusion of blood products should not be withheld from surgical patients as a means to prevent SSI . Conclusions and Relevance This guideline is intended to provide new and up date d evidence -based recommendations for the prevention of SSI and should be incorporated into comprehensive surgical quality improvement programs to improve patient safety	[ "Study Design . Prospect i ve r and omized trial . Objective . To explore the use of a microbial sealant applied before the surgical incision to reduce surgical site infection in patients with scoliosis . Summary of Background Data . The incidence of superficial or deep infections is reported in 2 groups of patients treated for neuromuscular or adolescent idiopathic scoliosis . Statistical analysis aim ed to compare the effect of the use of a cyanoacrylate microbial sealant on infection rate . Methods . From June 2010 to June 2011 , 56 patients were prospect ively enrolled in the study . Using a r and om number table , patients were assigned either to receive or not a sterile , film-forming cyanoacrylate liquid application ( Integuseal ) . Epidemiological data and infection occurrence were compared in both groups . Results . Statistical analysis comparing patients with neuromuscular scoliosis and adolescent idiopathic scoliosis showed that patients with neuromuscular scoliosis had more fused levels , increased intraoperative bleeding , and longer intraoperative time . Six patients had early postoperative infections of the posterior approach , which included 3 deep and 3 superficial infections . Five infections occurred in patients treated with Integuseal . Outcome was favorable in 6 cases after local wound debridement and antibiotics . Nonparametric statistical tests ( Fisher exact test ) showed no significant correlation ( P = 0.096 ) between early postoperative infection occurrence and the use of Integuseal . Conclusion . Although microbial sealant may be a useful addition to a multimodal approach to minimize surgical site infection , there is currently insufficient evidence as to whether the use of microbial sealants reduces the risk of surgical site infection in patients undergoing scoliosis surgery", "BACKGROUND Postoperative surgical site infections are one of the most frequent complications after open abdominal surgery , and triclosan-coated sutures were developed to reduce their occurrence . The aim of the PROUD trial was to obtain reliable data for the effectiveness of triclosan-coated PDS Plus sutures for abdominal wall closure , compared with non-coated PDS II sutures , in the prevention of surgical site infections . METHODS This multicentre , r and omised controlled group-sequential superiority trial was done in 24 German hospitals . Adult patients ( aged ≥18 years ) who underwent elective midline abdominal laparotomy for any reason were eligible for inclusion . Exclusion criteria were impaired mental state , language problems , and participation in another intervention trial that interfered with the intervention or outcome of this trial . A central web-based r and omisation tool was used to r and omly assign eligible participants by permuted block r and omisation with a 1:1 allocation ratio and block size 4 before mass closure to either triclosan-coated sutures ( PDS Plus ) or uncoated sutures ( PDS II ) for abdominal fascia closure . The primary endpoint was the occurrence of superficial or deep surgical site infection according to the Centers for Disease Control and Prevention criteria within 30 days after the operation . Patients , surgeons , and the outcome assessors were masked to group assignment . Interim and final analyses were by modified intention to treat . This trial is registered with the German Clinical Trials Register , number DRKS00000390 . FINDINGS Between April 7 , 2010 , and Oct 19 , 2012 , 1224 patients were r and omly assigned to intervention groups ( 607 to PDS Plus , and 617 to PDS II ) , of whom 1185 ( 587 PDS Plus and 598 PDS II ) were analysed by intention to treat . The study groups were well balanced in terms of patient and procedure characteristics . The occurrence of surgical site infections did not differ between the PDS Plus group ( 87 [ 14·8 % ] of 587 ) and the PDS II group ( 96 [ 16·1 % ] of 598 ; OR 0·91 , 95 % CI 0·66 - 1·25 ; p=0·64 ) . Serious adverse events also did not differ between the groups-146 of 583 ( 25·0 % ) patients treated with PDS Plus had at least one serious adverse event , compared with 138 of 602 ( 22·9 % ) patients treated with PDS II ; p=0·39 ) . INTERPRETATION Triclosan-coated PDS Plus did not reduce the occurrence of surgical site infection after elective midline laparotomy . Innovative , multifactorial strategies need to be developed and assessed in future trials to reduce surgical site infections . FUNDING Johnson & Johnson Medical Limited", "This multicenter prospect i ve study was performed to determine risk factors for knee prosthesis infection and the effect of timing doses of prophylactic low-molecular-weight heparins ( LMWH ) related to time of surgery on the risk of knee prosthesis infection . A total of 5496 consecutive patients who underwent total knee arthroplasty from 2005 to 2006 in 13 orthopedic centers were prospect ively followed up for 6 months , and the incidence of knee prosthesis infection was recorded . A case control study was nested in the cohort . Case patients were matched to uninfected ( control ) patients , and the timing of perioperative LMWH was recorded as the main risk factor . Fifty patients developed postoperative knee prosthesis infection during the follow-up period , yielding an incidence of prosthesis infection of 0.91 % ( 95 % CI , 0.68%-1.20 % ) . Forty-four patients were matched to 106 controls . Case patients received the first LMWH dose ±12 hours from the start of surgery more frequently than their control counterparts ( odds ratio , 1.5 ; 95 % CI , 0.73 - 3.0 ) . After adjusting by main risk factors , no statistical association was found between close perioperative timing of LMWH and risk of prosthesis infection . Diabetes mellitus ( adjusted odds ratio , 3.2 ; 95 % CI , 1.2 - 8.8 ) and wound hematoma ( adjusted odds ratio , 4.2 ; 95 % CI , 1.1 - 16.5 ) were found to be independent risk factors for prosthesis infection", "The results of 28 months of surveillance of postoperative wound infection rates in elective abdominal surgery using triple or single dose antimicrobial prophylaxis are reported . No significant differences in infection rates were seen in 217 patients undergoing gastric , biliary and pancreatic surgery who received either triple or single dose cefuroxime . Also , no significant differences in infection rates were seen in 198 patients undergoing jejunal , ileal and colorectal surgery who received either triple or single dose cefuroxime plus metronidazole . Our findings are consistent with those of other studies and support the conclusion that single dose prophylaxis is as effective as triple dose in elective abdominal surgery . During the study period there was no change in the pattern of bacteria isolated or in cefuroxime resistance rates from infected sites of patients from the Department of Surgery . No increased rate of cefuroxime resistance was seen in urinary isolates from patients elsewhere in the hospital", "BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations", "The amount of additional antibiotics measured by defined daily dose ( DDD ) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses ( 1502/1511 patients ) of cefuroxime . No differences were observed between the two regimens with respect to total amount , type , indication , and duration of additional antibiotics . The incidence of joint sepsis did not differ significantly between the two trial arms , but the sample was too small for definite conclusions . There were 11.4 DDD/100 bed days of additional antibiotics used in 21 % of patients after hip replacement and 15.7 DDD/100 bed days in 31 % after knee replacement . For wound problems , 3.8 and 6.9 DDD/100 bed days were given in the hip‐ and knee‐replacement groups . For distant infection , 6.5 DDD/100 bed days was administered in both groups . Duration of therapy varied only in relation to indication . Prescribed were penicillins ( 43 % to 50 % ) , sulfonamides ( 18 % ) , cephalosporins ( 10 % to 16 % ) , and nitrofurantoin ( 8 % to 13 % ) ; drug use was related to the type of infection", " Ninety-four patients undergoing vasectomy as day cases were studied prospect ively . An overall infection rate of 32.9 % was recorded and , apart from haematoma formation and the nasal carriage of organisms , no factors were found that increased the risk of infection . A preoperative hibiscrub shower did not affect the infection rate , even though it was responsible for a significant reduction in skin flora . This raises the possibility of infection following vasectomy being secondary , not occurring at the time of surgery", "OBJECTIVE To determine the role of postoperative antibiotics in reducing the surgical site infections ( SSIs ) after open appendectomy in patients with non-perforated appendicitis ( NPA ) . STUDY DESIGN R and omized controlled trial . PLACE AND DURATION OF STUDY The Department of Surgery , King Saud Medical City , Riyadh , Kingdom of Saudi Arabia , from January 2010 to July 2011 . METHODOLOGY Three hundred and seventy seven patients , who underwent appendectomy for NPA and fulfilled the selection criteria , were r and omized into two groups . The patients in group A received a single dose of pre- operative antibiotics ( cefuroxime sodium and metronidazole ) , while the group B patients received one more dose of the same antibiotics postoperatively . Patients of both the groups were followed-up for 30 days to assess the postoperative infective complications . RESULTS Group A had 195 , while group B comprised of 182 patients . The groups were comparable in the baseline characteristics . Statistically there was no significant difference in rates of SSIs between both the groups ( p = 0.9182 ) . Mean hospital stay was 2.29 ± 0.81 and 2.35 ± 0.48 days for group A and B respectively ( p = 0.4403 ) . None of the patients developed intraabdominal collection . CONCLUSION Single dose of pre-operative antibiotics ( cefuroxime and metronidazole ) was sufficient in reducing the SSIs after appendectomy for NPA . Postoperative antibiotics did not add an appreciable clinical benefit in these patients", "BACKGROUND Since the patient 's skin is a major source of pathogens that cause surgical-site infection , optimization of preoperative skin antisepsis may decrease postoperative infections . We hypothesized that preoperative skin cleansing with chlorhexidine-alcohol is more protective against infection than is povidone-iodine . METHODS We r and omly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint . The primary outcome was any surgical-site infection within 30 days after surgery . Secondary outcomes included individual types of surgical-site infections . RESULTS A total of 849 subjects ( 409 in the chlorhexidine-alcohol group and 440 in the povidone-iodine group ) qualified for the intention-to-treat analysis . The overall rate of surgical-site infection was significantly lower in the chlorhexidine-alcohol group than in the povidone-iodine group ( 9.5 % vs. 16.1 % ; P=0.004 ; relative risk , 0.59 ; 95 % confidence interval , 0.41 to 0.85 ) . Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections ( 4.2 % vs. 8.6 % , P=0.008 ) and deep incisional infections ( 1 % vs. 3 % , P=0.05 ) but not against organ-space infections ( 4.4 % vs. 4.5 % ) . Similar results were observed in the per- protocol analysis of the 813 patients who remained in the study during the 30-day follow-up period . Adverse events were similar in the two study groups . CONCLUSIONS Preoperative cleansing of the patient 's skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing surgical-site infection after clean-contaminated surgery . ( Clinical Trials.gov number , NCT00290290 .", "In a r and omized prospect i ve trial of prophylactic antibiotics in at-risk abdominal surgery , one dose of intravenous Augmentin ( amoxycillin 250 mg and clavulanic acid 125 mg ) on induction has been compared with three 8 hourly doses in 900 patients . Wound infection rates which included minor and delayed infections were very similar in those given one dose : 48/449 ( 10.7 % ) compared with those given three doses : 49/451 ( 10.9 % ) 95 % confidence limits - 4.25 % + 3.9 % . There were more septic and sepsis-related deaths in those patients given one dose ( 14 deaths ) than in those given three doses ( 7 deaths ) P > 0.1 95 % CL - 0.4 % + 3.0 % . However , there were more very elderly patients in the one dose group : 64 % of the deaths were aged over 80 and all but one had an emergency operation . There was no difference in the other outcome measures studied which included non-fatal deep sepsis , length of postoperative hospital stay , duration of postoperative fever or the use of antibiotics for postoperative infection . One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses . However , there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery", ": We are revising the Medicare hospital inpatient prospect i ve payment systems ( IPPS ) for operating and capital-related costs of acute care hospitals to implement changes arising from our continuing experience with these systems and to implement certain provisions of the Affordable Care Act and other legislation . In addition , we describe the changes to the amounts and factors used to determine the rates for Medicare acute care hospital inpatient services for operating costs and capital-related costs . We also are setting forth the up date to the rate-of-increase limits for certain hospitals excluded from the IPPS that are paid on a reasonable cost basis subject to these limits . We are updating the payment policy and the annual payment rates for the Medicare prospect i ve payment system ( PPS ) for inpatient hospital services provided by long-term care hospitals ( LTCHs ) and setting forth the changes to the payment rates , factors , and other payment rate policies under the LTCH PPS . In addition , we are finalizing the provisions of the August 27 , 2009 interim final rule that implemented statutory provisions relating to payments to LTCHs and LTCH satellite facilities and increases in beds in existing LTCHs and LTCH satellite facilities under the LTCH PPS . We are making changes affecting the : Medicare conditions of participation for hospitals relating to the types of practitioners who may provide rehabilitation services and respiratory care services ; and determination of the effective date of provider agreements and supplier approvals under Medicare . We are also setting forth provisions that offer psychiatric hospitals and hospitals with inpatient psychiatric programs increased flexibility in obtaining accreditation to participate in the Medicaid program . Psychiatric hospitals and hospitals with inpatient psychiatric programs will have the choice of undergoing a State survey or of obtaining accreditation from a national accrediting organization whose hospital accreditation program has been approved by CMS . We are also issuing an interim final rule with comment period to implement a provision of the Preservation of Access to Care for Medicare Beneficiaries and Pension Relief Act of 2010 relating to Medicare payments for outpatient services provided prior to a Medicare beneficiary 's inpatient admission", "OBJECT Implantation of cerebrospinal fluid ( CSF ) shunting devices is associated with a 5 - 15 % risk of infection as cited in contemporary pediatric neurosurgical literature . Shunt infections typically require complete removal of the device and prolonged antibiotic treatment followed by shunt replacement . Moreover , shunt infections are commonly associated with prolonged hospital stays , potential comorbidity , and the increased risk of neurological compromise due to ventriculitis or surgical complications . The authors prospect ively evaluated the incidence of CSF shunt infection following shunt procedures performed using either antimicrobial suture ( AMS ) or conventional suture . METHODS In a single-center , prospect i ve , double-blinded , r and omized controlled trial , the authors enrolled 61 patients , among whom 84 CSF shunt procedures were performed over 21 months . R and omization to the study ( AMS ) or control ( placebo ) group was stratified to minimize the effect of known shunt infection risk factors on the findings . Antibacterial shunt components were not used . The primary outcome measure was the incidence of shunt infection within 6 months of surgery . RESULTS The shunt infection rate in the study group was 2 ( 4.3 % ) of 46 procedures and 8 ( 21 % ) of 38 procedures in the control group ( p = 0.038 ) . There were no statistically significant differences in shunt infection risk factors between the groups ( procedure type and time , age suture-related adverse events were reported in either group . CONCLUSIONS These results support the suggestion that the use of AMS for CSF shunt surgery wound closure is safe , effective , and may be associated with a reduced risk of postoperative shunt infection . A larger r and omized controlled trial is needed to confirm this association", "Background : Obese patients are at a high risk of postoperative complication , including surgical site infection ( SSI ) . Our aim was to evaluate the effect of a high inspiratory oxygen fraction ( 80 % ) on SSI and pulmonary complications in obese patients undergoing laparotomy . Methods : This study was a planned analysis of the obese patients ( body mass index ≥ 30 kg/m2 ) recruited in the Danish multicenter , patient- and observer-blinded , PROXI Trial of 1,400 patients undergoing acute or elective laparotomy . Patients were r and omized to receive either 80 % or 30 % oxygen during and for 2 h after surgery . The primary outcome was SSI within 14 days . Secondary outcomes were atelectasis , pneumonia , and respiratory failure . Results : Two hundred thirteen patients had a body mass index ≥ 30 kg/m2 . The median ( 5–95 % range ) body mass index was 34 kg/m2 ( 30–44 ) and 33 kg/m2 ( 30–41 ) in patients allocated to the 80 % and 30 % oxygen group . SSI occurred in 32 of 102 ( 31 % ) versus 29 of 111 ( 26 % ) patients given 80 % and 30 % oxygen , respectively ( odds ratio , 1.29 ; 95 % CI , 0.71–2.34 ; P = 0.40 ) . In addition , the incidence of pulmonary complications was not significantly different , with atelectasis occurring in 9 % versus 6 % , pneumonia in 6 % versus 5 % , and respiratory failure in 8 % versus 5 % in patients given 80 % and 30 % oxygen , respectively . Conclusion : Administration of 80 % oxygen , compared with 30 % oxygen , did not reduce the frequency of SSI in obese patients . Moreover , no significant association was found between oxygen fraction and the risk of pulmonary complications ", "A prospect i ve r and omized trial was performed comparing the efficacy of intraperitoneal irrigation with low molecular weight povidone-iodine solution ( ' Betadine LMW ' ) ( PVP-I LMW ) in reducing the risk of intra-abdominal infectious complications . Seventy-five patients who were undergoing surgical procedures in the face of bacterial contamination were studied . Patients were intra-operatively r and omized to receive intraperitoneal irrigation prior to abdominal closure with PVP-I LMW or with saline . Patients were maintained on peri-operative systemic antibiotics , and surgical incisions were drained and were closed primarily or left open according to the practice of the surgeon responsible . If incisions were closed , the subcutaneous tissue was irrigated prior to skin closure with the same irrigant as used intraperitoneally , PVP-I LMW or saline . Patients were followed for abnormal wound healing , peritonitis , intra-abdominal abscesses , or other infectious complications . Serum iodine levels were monitored in some patients . Intra-abdominal infectious complications developed in two of 37 patients receiving PVP-I LMW irrigation as compared to complications in nine of 38 patients receiving saline irrigation ( P less than 0.05 ) . When infectious complications were excluded that were possibly due to surgical technical failures ( such as anastomotic leakage ) , peritonitis or intra-abdominal abscesses were observed in one of 37 PVP-I LMW patients and in seven of 38 saline control patients ( P less than 0.05 ) . Wound infections developed in one of 37 PVP-I LMW patients and in three of 38 control patients . A broad range of serum iodine levels were observed in control patients preoperatively and at 24 h and 7 days postoperatively . Serum iodine levels in ' Betadine LMW ' patients rose approximately nine-fold by 24 h postoperatively and returned to pre-operative levels by 7 days . It was concluded that PVP-I LMW solution can reduce the incidence of intra-abdominal infectious complications when used as an intraperitoneal irrigant in patients undergoing bacterially-contaminated surgical procedures", "A prospect i ve r and omized trial compared antiseptic solutions and normal saline as a means of preventing morbidity and mortality from residual sepsis in patients with generalized peritonitis . Fifty-three patients , all given broad-spectrum antibiotics , were entered into the study . Twenty patients received a saline lavage , 19 lavage with chlorhexidine-gluconate and 14 a saline lavage with instillation of povidone-iodine . All deaths were due either to the severity of the presenting disease or co-existing complicating conditions . The incidence of postoperative pyrexia , wound infection and duration of hospital stay of the surviving patients were unaffected by lavage grouping", "CONTEXT Perioperative antibiotic prophylaxis during elective cesarean delivery at term to reduce postoperative maternal infectious morbidity is generally used but may not be effective on the basis of the available data . Also , the optimal timing of prophylactic antibiotic administration is unclear . OBJECTIVE To compare the effectiveness of cefazolin administered before skin incision vs cefazolin administered after umbilical cord clamping vs placebo in a 3-arm r and omized trial . The primary objective of the study was to compare postoperative infectious morbidity , defined as wound infection , endometritis , or urinary tract infection ( primary end point ) , in women with cefazolin vs placebo . The comparison between the 2 arms administering cefazolin before skin incision vs after umbilical cord clamping was a secondary end point . DESIGN Double-blind , prospect i ve , r and omized , placebo-controlled trial . SETTING The Department of Obstetrics and Gynecology , Medical University of Vienna , Vienna , Austria . PATIENTS We recruited 1112 women undergoing elective cesarean delivery at term from March 1 , 2004 , through January 31 , 2010 . INTERVENTIONS In group 1 , cefazolin ( 2 g ) was administered 20 to 30 minutes before skin incision . In group 2 , cefazolin ( 2 g ) was administered immediately after clamping of the cord . In group 3 , placebo was administered before skin incision . RESULTS The primary outcome was observed in 18 of 370 women in group 1 ( 4.9 % ) and in 14 of 371 women in group 2 ( 3.8 % ) , whereas it was noted in 45 of 371 women in group 3 ( 12.1 % ) ( P postoperative infectious morbidity ( P = .60 ) . CONCLUSION We were able to demonstrate the usefulness in elective cesarean delivery of prophylactic cefazolin vs placebo in reducing postoperative maternal infectious morbidity", "Abstract Povidone-iodine and chlorhexidine surgical scrub and skin preparation solutions were assessed by comparing postoperative wound infection rates in a prospect i ve , r and omized study of 866 patients . The frequency of wound infection overall , as agreed by two observers , was 14·8 per cent in the povidone-iodine group and 9·7 per cent in the chlorhexidine group ( P = 0·03 ) at the time of patients ' discharge from hospital . The difference between the compounds was not significant at a ‘ st and ard ' observation period of three to four days after operation . There were significantly fewer infections with chlorhexidine than with povidone-iodine in operations on the biliary tract and in ‘ clean ' non-abdominal operations , but there were more infections ( not significantly so ) with chlorhexidine than with povidoneiodine in large bowel surgery , other laparotomies and in operations on hernia , genitalia and varicose veins . The differences in bacterial isolates from wounds tended to follow the above patterns . We conclude that , on the evidence of this study , there is no overwhelming case for using one compound rather than the other as an all- purpose preparation and scrub", "In a prospect i ve controlled trial , 750 patients undergoing elective biliary , gastric or colorectal surgery were r and omized to receive short-term or long-term antibiotic prophylaxis -- cefotaxime for biliary or gastric , and gentamicin/metronidazole for colorectal operations . In all patients , delayed cutaneous hypersensitivity was preoperatively assessed by simultaneous application of seven st and ardized recall antigens . Positive reaction was defined as mean diameter greater than or equal to 2 mm , anergy as no positive reaction to any antigen , and a ' score ' as the sum ( in mm ) of all the mean diameters of positive reactions . There was no significant difference in septic complication or mortality rates following short-term vs. long-term prophylaxis . Anergy was found in 21 patients ( 2.8 % ) , while 63 ( 8.4 % ) scored 2 - 4 and 666 ( 88.8 % ) greater than or equal to 5 . The incidence of postoperative infectious complications was 25 % in the patients with score less than 5 and 10 % in those scoring greater than or equal to 5 , and the corresponding mortality was 14.3 and 2.1 % ( both p less than 0.001 ) . In the group with preoperative scores less than 5 , the duration of antibiotic prophylaxis influenced neither postopertive infectious complications nor mortality", "HYPOTHESIS Deep infection after shoulder surgery is a rare but devastating problem . This study tested the hypothesis that the home application of a 2 % chlorhexidine gluconate cloth before shoulder surgery would be more efficacious than a st and ard shower of soap and water at decreasing the preoperative cutaneous levels of pathogenic bacteria on the shoulder . MATERIAL S AND METHODS This r and omized , prospect i ve study evaluated 100 consecutive patients undergoing shoulder surgery . Patients were r and omly assigned to use 2 % chlorhexidine gluconate-impregnated cloths ( treatment group ) or to shower with soap and water before surgery ( control group ) . Cutaneous cultures were taken from the patients ' shoulders in the preoperative holding area . Patients were monitored for 2 months postoperatively for clinical signs of infection . RESULTS In the treatment group vs the control group , the overall positive culture rate was 66 % vs 94 % ( P = .0008 ) , and the positive culture rate for coagulase-negative Staphylococcus was 30 % vs 70 % ( P = .0001 ) . The positive culture rate for Propionibacterium acnes was 46 % in the treatment group vs 58 % in the control group ( P = .32 ) . No infections occurred in any patients at a minimum of 2-months after surgery . DISCUSSION The use of the 2 % chlorhexidine cloth was effective at decreasing overall bacterial culture rates before shoulder surgery and was particularly effective at decreasing the quantity of coagulase-negative Staphylococcus , a known causative agent of postoperative shoulder infections . CONCLUSION Use of chlorhexidine impregnated cloths prior to shoulder surgery may be a useful adjunct to presently used infection prevention strategies", "Intra-operative incidental contamination of surgical wounds is not rare . Povidone-iodine solution can be used to disinfect surgical wounds . Although povidone-iodine is a good broad-spectrum disinfecting agent , it has occasionally been reported to have a negative effect on wound healing and bone union . Therefore , its safety in a spinal surgery is unclear . A prospect i ve , single-blinded , r and omized study was accordingly conducted to evaluate the safety of povidone-iodine solution in spinal surgeries . Ascertained herein was the effect of wound irrigation with diluted povidone-iodine solution on wound healing , infection rate , fusion status and clinical outcome of spinal surgeries . Material s and methods : From January 2002 to August 2003 , 244 consecutive cases undergoing primary instrumented lumbosacral posterolateral fusion due to degenerative spinal disorder with segmental instability had been collected and r and omly divided into two groups : the study group ( 120 cases , 212 fusion levels ) and the control group ( 124 cases , 223 fusion levels ) . Excluded were those patients with a prior spinal surgery , spinal trauma , malignant tumor , infectious spondylitis , rheumatoid arthritis , ankylosing spondylitis , metabolic bone disease , skeletal immaturity or with an immunosuppressive treatment . In the former group , wounds were irrigated with 0.35 % povidone-iodine solution followed by normal saline solution just before the bone-grafting and instrumentation procedure . However , only with normal saline solution in the latter . All the operations were done by the same surgeon with a st and ard technique . All the patients were treated in the same postoperative fashion as well . Later on , wound healing , infection rate , spinal bone fusion and clinical outcome were evaluated in both groups . Results : A significant improvement of back and leg pain scores , modified Japanese Orthopedic Association function scores ( JOA ) and ambulatory capacity have been observed in both groups . One hundred and seven patients in the study group and one hundred and nine in the control group achieved solid union . There was no infection in the study group but six deep infections in the control group . Wound dehiscence was noted in one group 1 and two group 2 patients . A subsequent statistical analysis revealed higher infection rate in the control group ( P fusion rate , wound healing , improvement of pain score , function score and ambulatory capacity between the two groups . Conclusion : Diluted povidone-iodine solution can be used safely in spinal surgeries , and it will not influence wound healing , bone union and clinical outcome", "Background and Objectives : Umbilical port-site infections after video-laparoscopic cholecystectomy ( VLC ) are frequent complications . The aim of this prospect i ve r and omized study was to verify the validity of topical rifamycin for prevention of post-VLC umbilical infections . Methods : From September 2006 to April 2007 , 48 patients with uncomplicated cholelithiasis who underwent VLC were enrolled in the study . Enrolled patients were r and omized into 2 groups . The first group of 24 patients was treated with topical rifamycin to the umbilicus . The second group of 24 patients was not treated with rifamycin . Results : Postoperative umbilical pain with a need for analgesics , presence of signs of inflammation of the umbilical wound , dehiscence of the umbilical skin sutures , and the presence of incisional umbilical hernia on the 60th postoperative day were statistically significantly better in the rifamycin group compared with the control group . Conclusions : Topical administration of rifamycin to the umbilicus in the pre- , intra- and postoperative periods was a rapid , safe , and economic way to reduce infective complications after VLC", "BACKGROUND Surgical site infection ( SSI ) is the fourth commonest healthcare-associated infection and complicates at least 5 % of open operations . In a r and omized clinical trial , antimicrobial-coated sutures were compared with their conventional counterparts , polyglactin and poliglecaprone , for skin closure after breast cancer surgery to assess their role in reducing the rate of SSI . METHODS Between November 2008 and February 2011 , 150 female patients presenting with breast cancer to a single center were r and omized to skin closure with antimicrobial-coated or plain sutures . Postoperatively , SSI was defined using the U.S. Centers for Disease Control and Prevention ( CDC ) definitions and scored using the ASEPSIS or Southampton systems by trained , blinded observers with close post-discharge surveillance and patient diaries . Surgeons and patients were blinded to the type of suture used . RESULTS Using CDC criteria , the overall rate of SSI was 18.9 % at six weeks . Six patients ( 4.7 % ) needed intervention or readmission for SSI . Skin closure with antimicrobial sutures showed a non-statistically significant reduction in the SSI rate , to 15.2 % , compared with conventional sutures ( 22.9 % ) . A uniform tendency for fewer SSIs in the antimicrobial-coated suture group was found using ASEPSIS and Southampton scores , but again , the difference was not statistically significant . CONCLUSION The previously reported high rate of SSI related to breast surgery was confirmed . Using statistical modeling and earlier reports , the study was powered to show a difference using ASEPSIS scores , but the modification used in this trial failed to find a difference . Finding a statistically significant difference would have needed two to three times the number of patients recruited . Further evaluation of antimicrobial-coated sutures is merited , particularly if used as part of a care bundle to reduce SSI after breast cancer surgery", "BACKGROUND / PURPOSE Despite general recommendation of short-course antibiotic prophylaxis , prolonged antibiotic use is still commonly reported in clinical setting s. This study compared the efficacy of 1-day versus 3-day antibiotic prophylaxis in preventing surgical site infection ( SSI ) in patients undergoing coronary artery bypass graft ( CABG ) . METHODS This prospect i ve , r and omized control study was performed in a tertiary-care medical center from June 2002 to April 2004 . Patients underwent non-emergency CABG and were r and omized into two groups receiving either 1 day or 3 days cefazolin prophylaxis . The SSI rates were compared between the two groups . RESULTS During the study period , 231 patients were enrolled , 120 in the 1-day group and 111 in the 3-day group . Twenty-two episodes of SSI were observed within 1 month after operation : 13 ( 10.8 % ) in the 1-day group and nine ( 8.1 % ) in the 3-day group ( odds ratio : 1.37 ; 95 % confidence interval : 0.56 - 3.33 ; p = 0.48 ) . By logistic regression analysis , 1-day prophylaxis with cefazolin was not associated with higher risk of SSI ( adjusted odds ratio : 0.91 ; 95 % confidence interval : 0.32 - 2.56 ; p = 0.85 ) . CONCLUSION Antibiotic prophylaxis for 1 day in CABG surgery was associated with similar rates of postoperative infection compared with antibiotic prophylaxis of 3 days", "Objective The aim of this study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal and neonatal infectious morbidity . Study design This was a prospect i ve , r and omized trial . Four hundred patients that underwent elective cesarean section between June and December 2007 formed the study population . Eleven patients were excluded from the study because they needed transfusion during the cesarean section . The population was divided into two groups : Group A , antibiotic prophylaxis was applied to 194 women before skin incision and Group B , antibiotic prophylaxis was applied to 195 women after umbilical cord clamping . The occurrence of endomyometritis/endometritis , wound infection , febrile morbidity , total infectious morbidity , and neonatal complications were compared . Results There were 389 patients enrolled . No demographic differences were observed between groups . No significant difference was found between the groups for total infectious morbidity [ relative risk ( RR ) 1.39 , 95 % confidence interval ( CI ) 0.71–2.69 ] and endometritis ( RR 1.40 , 95 % CI 0.43–4.51 ) . There was no increase in neonatal sepsis ( RR 1.47 , 95 % CI 0.61–3.53 ) , sepsis workup ( RR 1.35 , 95 % CI 0.75–2.42 ) , need for neonatal intensive care ( RR 1.77 , 95 % CI 0.51–6.16 ) , and intensive care stay period ( P = 0.16 ) . Conclusions Time of antibiotic prophylaxis application does not change maternal infectious morbidity in cesarean section deliveries . Preoperative prophylaxis application does not affect neonate morbidity rates as stated in literature", "We conducted a prospect i ve r and omized controlled double-blind trial at a regional referral centre for the Eastern Cape area , ( Livingstone Hospital ) to determine whether the use of plastic adhesive drapes intraoperatively would prevent Post Caesarean Section Wound Infection . A total of 620 patients undergoing Caesarean section ( CS ) were enrolled for r and omization in the trial . Fifteen patients were excluded , while 305 received drapes ( test group ) and 300 did not ( control group ) . Two patients in the control group were subsequently excluded . The primary outcome measure was the presence of Post Caesarean Wound Infection . A secondary outcome measure was the number of days in hospital post operation . The study and control groups were comparable at entry . Results show that 34 patients in the test group ( N= 305 ) developed wound sepsis ( 11.1 % ) compared with 30 in the control group ( N= 298 ) ( 10.1 % ) ( difference not significant ; Fisher 's exact test 0.6933 ) . Average days spent in hospital postoperatively were similar for both test ( infected cases : mean 10.56 SD 3.84 ; non-infected cases : mean 5.21 SD 1.3 ) and control groups ( infected cases : mean 10.18 SD 3.81 ; non-infected cases : mean 5.2 SD 0.93 ) ( NS ) . We concluded that the use of plastic adhesive skin drapes did not avert PCWS or decrease the length of post operative stay in hospital for septic cases", "BACKGROUND : Patients who undergo colorectal surgery have up to a 30 % chance of developing a surgical site infection postoperatively . Silverlon is a silver nylon dressing design ed to prevent surgical site infections , but only anecdotal evidence has previously supported its efficacy . OBJECTIVE : The aim of this study was to evaluate the effect of silver nylon dressings in patients undergoing colorectal surgery . DESIGN : We performed a prospect i ve , r and omized , controlled trial comparing a silver nylon dressing with gauze dressings in patients undergoing elective colorectal surgery . SETTING : The study was performed at a university-based , tertiary referral center . PATIENTS : We studied patients undergoing elective colorectal surgery with an abdominal skin incision of at least 3 cm . INTERVENTION : Patients were r and omly assigned to receive either a silver nylon or a gauze dressing . MAIN OUTCOME MEASURES : The primary end point was surgical site infection occurring within 30 days of surgery . RESULTS : One hundred ten patients were enrolled in the study and were r and omly assigned to 1 of 2 treatment groups . After a 30-day follow-up period , the incidence of surgical site infection was lower in the silver nylon group compared with the control group ( 13 % vs 33 % , P = .011 ) . Twenty-five patients in the study developed superficial surgical site infections , 5 in the silver nylon group and 14 in the control group ( P = .021 ) . Two patients in the study group developed deep wound infections compared with 4 in the control group ( P = .438 ) . Multivariate analysis revealed that patients in the control group had a 3-fold increase in risk of infection compared with patients in the silver nylon group ( P = .013 ) . LIMITATIONS : A limitation of this study is that the members of the surgical team were not blinded to the treatment groups . CONCLUSION : Silver nylon is safe and effective in preventing surgical site infection following colorectal surgery", "In this prospect i ve , r and omized study of 187 patients undergoing a variety of general surgical procedures , no significant difference could be demonstrated between those patients whose wounds were irrigated with normal saline solution and those whose wounds were irrigated with povidone-iodine . The potential of an alpha or a beta error is discussed", " OBJECTIVE To evaluate the efficacy and safety of new antibacterial suture ( Vicryl Plus ) compared with a traditional braided suture ( Vicryl ) in a clinical study . The primary goal was to study effectiveness on reduced surgical site infection in an appendectomy operation . The authors ' secondary goal was to analyze the safety and physical properties of Vicryl plus . MATERIAL AND METHOD This was a prospect i ve , r and omized , controlled , double blind , comparative , single-center study . After appendectomy was done , the patients were r and omized in two groups : Vicryl Plus and Vicryl to selected suture for suturing the abdominal sheath . The surgical site infection was evaluated for 30 days , 6 months , and 1 year . The surgeons and attending doctor were blind to the type of suture . This is the primary report of the first 100 patients . RESULTS There was no difference in demographic and preoperative clinical in both groups . Although there was no statistical difference in the surgical site infection of Vicryl and Vicryl Plus ( 8 and 10 % , p = 0.05 ) , one case of deep surgical site infection was detected in the Vicryl group . No complications and no difference in related suture material s were detected . CONCLUSION Coated polyglactin 910 with tricosan ( Vicryl Plus ) is safe and satisfactory in surgical practice . Surgical site infection of appendectomy seemed too to be comparable between coated polyglactin 910 with tricosan ( Vicryl Plus ) and traditional polyglactin 910 ( Vicryl ) group", "Background : The effect of extended prophylactic antibiotic therapy on postoperative infective complications such as wound infection and intra‐abdominal abscess for non‐perforated appendicitis is poorly defined", "We compared maternal and neonatal outcomes in women who received prophylactic antibiotics prior to skin incision to those who received antibiotics at cord clamp . We performed a r and omized clinical trial at two sites . Eligible women included those undergoing nonemergency cesarean at 36 weeks ' gestation or greater . Subjects were r and omized ( permuted blocks ) into one of two treatments : \" preoperative antibiotics \" ( cefazolin 1 g given . Patients who reported an allergy to penicillin received clindamycin 900 mg . The trial primary outcome was a composite of maternal infectious morbidities , defined as having any one of the following : ( 1 ) postoperative fever ( defined as oral temperature > 38 ° C on two separate occasions more than 6 hours apart , after the initial 24-hour postoperative period ) ; ( 2 ) wound infection ( defined as purulent discharge from the incision ) ; ( 3 ) endomyometritis ( defined as fundal tenderness and fever malodorous lochia , fever ) ; ( 4 ) urinary tract infection ( defined as fever , positive urine culture ) . We enrolled a total of 434 subjects in this study , with 217 in each group . Overall , we found no difference in composite maternal infectious morbidity between those who received antibiotics preoperatively and those who received antibiotics at cord clamp ( relative risk = 1.2 , 95 % confidence interval 0.7 to 1.5 ) . Neonatal outcomes were also similar between the two intervention arms . The rate of suspected sepsis was similar between the two groups . There were no cases of antibiotic resistance in the neonates . Either preoperative antibiotic therapy or antibiotic administration after cord clamp is a reasonable clinical method for reducing the risk of postcesarean infectious morbidity ", "Background An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery . We decided to test this finding in a r and omized , double-blind trial . Methods Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were r and omly assigned to have the surgical incision dressed with Aquacel ® Ag Hydrofiber dressing or a common dressing . To blind the patient and the nursing and medical staff to the nature of the dressing used , scrub nurses covered Aquacel ® Ag Hydrofiber with a common wound dressing in the experimental arm , whereas a double common dressing was applied to patients of control group . The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery . Results A total of 112 patients ( 58 in the experimental arm and 54 in the control group ) qualified for primary end-point analysis . The characteristics of the patient population and their surgical procedures were similar . The overall rate of surgical-site infection was lower in the experimental group ( 11.1 % center 1 , 17.5 % center 2 ; overall 15.5 % ) than in controls ( 14.3 % center 1 , 24.2 % center 2 , overall 20.4 % ) , but the observed difference was not statistically significant ( P = 0.451 ) , even with respect to surgical-site infection grade 1 ( superficial ) versus grade s 2 and 3 , or grade 1 and 2 versus grade 3 . Conclusions This r and omized trial did not confirm a statistically significant superiority of Aquacel ® Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery . Trial registration Clinical trials.gov :", "BACKGROUND Previous studies have demonstrated higher infection rates following orthopaedic procedures on the foot and ankle as compared with procedures involving other areas of the body . Previous studies also have documented the difficulty of eliminating bacteria from the forefoot prior to surgery . The purpose of the present study was to evaluate the efficacy of three different surgical skin-preparation solutions in eliminating potential bacterial pathogens from the foot . METHODS A prospect i ve study was undertaken to evaluate 125 consecutive patients undergoing surgery of the foot and ankle . Each lower extremity was prepared with one of three r and omly selected solutions : DuraPrep ( 0.7 % iodine and 74 % isopropyl alcohol ) , Techni-Care ( 3.0 % chloroxylenol ) , or ChloraPrep ( 2 % chlorhexidine gluconate and 70 % isopropyl alcohol ) . After preparation , quantitative culture specimens were obtained from three locations : the hallux nailfold ( the hallux site ) , the web spaces between the second and third and between the fourth and fifth digits ( the toe site ) , and the anterior part of the tibia ( the control site ) . RESULTS In the Techni-Care group , bacteria grew on culture of specimens obtained from 95 % of the hallux sites , 98 % of the toe sites , and 35 % of the control sites . In the DuraPrep group , bacteria grew on culture of specimens obtained from 65 % of the hallux sites , 45 % of the toe sites , and 23 % of the control sites . In the ChloraPrep group , bacteria grew on culture of specimens from 30 % of the hallux sites , 23 % of the toe sites , and 10 % of the control sites . ChloraPrep was the most effective agent for eliminating bacteria from the halluces and the toes ( p chlorhexidine and alcohol ( ChloraPrep ) was most effective for eliminating bacteria from the forefoot prior to surgery", "OBJECTIVE Postoperative surgical site infections ( SSI ) still greatly affect mortality and morbidity in cardiovascular surgery . SSI may be related to the suture material . In this prospect i ve , r and omized , controlled , and double-blinded study , the effect of antibacterial suture material on SSI in cardiac surgical patients was investigated . METHODS We r and omly allocated 510 patients into 2 groups . Antibacterial suture material s were used for wound closure in 170 patients ( triclosan-coated suture group ) , and routine suture material s were used in 340 patients ( noncoated suture group ) . All patients were evaluated for SSI on days 10 , 20 , and 30 following cardiac surgery . RESULTS Preoperative risk factors and laboratory findings were comparable for the 2 groups . Sternal infection occurred in 4 ( 2.4 % ) of the patients in the triclosan-coated suture group and in 3.5 % of the noncoated suture group ( P > .05 ) . Leg wound infection occurred in 5 ( 3.5 % ) of the patients in the triclosan-coated suture group and in 3.8 % of the noncoated suture group ( P > .05 ) . Only diabetes mellitus was an independent predictor of SSI . CONCLUSION Both noncoated and triclosan-coated suture material s are safe . Larger studies may be needed to show the benefit and cost-effectiveness , if any , of triclosan-coated material s over noncoated material", "Background : Benefits and limitations of supplementation with 80 % fraction of inspired oxygen for preventing surgical site infections have not yet been clearly defined . Some studies have reported benefits in colorectal surgery , whereas trials in abdominal and gynecologic surgery have reported either no effect or a deleterious effect . Methods : Controlled , r and omized , assessor-blind multicenter trial , the ISO2 study , comparing the effects of hyperoxygenation ( fraction of inspired oxygen , 80 % ) with those of 30 % oxygen on the frequency of surgical site infections in routine abdominal , gynecologic , and breast surgery on 434 patients . Patients not seen in consultation after discharge were contacted . Results : In total , 208 patients received 30 % perioperative oxygen and 226 received 80 % . There was no difference between the two groups for baseline , intraoperative , and postoperative characteristics , except for oxygen saturation at closure , higher in the 80 % group ( P = 0.01 ) . The frequency of 30-day surgical site infections was 7.2 % ( 15/208 ) in the 30 % group and 6.6 % ( 15/226 ) in the 80 % group ( relative risk , 0.92 ; 95 % CI [ 0.46–1.84 ] , P = 0.81 ) . Frequency of adverse events ( nausea and vomiting , sternal pain , cough , hypotension ) was similar in the two groups . Desaturation and bradycardia were more frequent in the 30 % group . In an up date d meta- analysis including the result of this trial and those of eight published r and omized trials , the overall relative risk was 0.97 ; 95 % CI ( 0.68–1.40 ) , I2 ( inconsistency degree ) = 73 % , ( P = 0.88 ) . Conclusions : The routine use of hyperoxygenation throughout abdominal , gynecologic , and breast surgery had no effect on the frequency of 30-day surgical site infections and was not accompanied by more frequent adverse effects", "The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity . Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were r and omized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded , placebo-controlled study . The 2 groups were compared for differences in maternal and neonatal demographics , and intrapartum and operative characteristics associated with postcesarean infection . Primary maternal outcome variables were endometritis or wound infection . Secondary outcomes included intra-abdominal abscess formation , septic pelvic thrombophlebitis , pneumonia , or urinary tract infection . Neonatal outcomes included sepsis screens , sepsis , pneumonia , and meningitis . Subjects were followed 6 weeks postoperatively for late complications . Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics , and intrapartum and operative characteristics . One patient in the former group experienced both endometritis and wound infection . In the latter group , 2 wound infections and 1 case of endometritis occurred ( P = 0.35 ) . There were no secondary maternal infections . Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively . Overall , 8 neonates were evaluated for suspected sepsis and all had negative studies . Six of these infants ' mothers received cefazolin preoperatively ( P = 0.28 ) . In conclusion , 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity , but is associated with a trend toward increased suspected sepsis in the newborn . However , this trend may be related to differences between the study groups ' risk factors for infection", "BACKGROUND This r and omized clinical trial compares the incidence of wound infection after vascular surgery in patients who received prophylaxis using the same antibiotic as either a single-dose or a multiple-dose regimen ( until the lines/drain tubes were removed , but not for more than 5 days ) . METHODS Each of the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1 g ( Timentin ) intravenously immediately after the induction of anesthesia . Patients r and omized to the multiple-dose group received an average of 14.3 doses ( range 9 to 20 ) . RESULTS The incidence of wound infections was 18 % ( 28 of 153 ) for patients in the single-dose group and 10 % ( 15 of 149 ) for patients in the multiple-dose group ( P = 0.04 ; relative risk estimate = 2.00 , 95 % confidence interval = -1.02 to 3.92 ) . CONCLUSIONS A multiple-dose antibiotic regimen , rather than single-dose therapy , provides optimal prophylaxis against wound infection for patients undergoing vascular surgery", "OBJECTIVES Leg wound infection is a common complication after coronary artery bypass grafting ( CABG ) . Suture contamination has been suggested as a mechanism of surgical site infections . Vicryl Plus ( ® ) is a polyglacitin suture coated with the antiseptic chemical substance Triclosan , which has been shown to inhibit the growth of Staphylococcus aureus in vitro . The first aim of the present study was to compare Vicryl Plus with conventional Vicryl ( ® ) sutures with regard to leg wound infections following CABG . The second aim was to examine patient- and operative characteristics , which are assumed to predict leg wound infections . METHODS After statistical calculations a priori , 328 CABG patients were prospect ively r and omized to leg wound closure with Vicryl Plus ( 164 patients ) or conventional Vicryl sutures ( 164 patients ) . Incidences of leg wound infection and predictors of infection related to patient- and operative characteristics were examined . RESULTS The incidence of leg wound infections was 10.4 % ( 17/163 ) in the Vicryl group , and 10.0 % ( 16/160 ) in the Vicryl Plus group ( P = 1.00 ) . Patients with leg wound infections had increased body mass index and prolonged extracorporeal circulation and aortic clamping time compared with patients without infections . CONCLUSIONS In the present study , we report for the first time that Vicryl Plus did not reduce the incidence of leg wound infections in patients undergoing CABG . Obesity and prolonged time of extracorporeal circulation were both associated with the increased risk of infections . Currently , the clinical role and indication for the use of Vicryl Plus have yet to be defined", "A prospect i ve r and omized blinded study was conducted comparing a single 2-g preoperative dose of cefoxitin with three 2-g doses of cefoxitin over 12 hours given to premenopausal women scheduled for vaginal hysterectomy in Parkl and Memorial Hospital . The incidence of major pelvic infection in 58 women given one dose was 1.7 % , and it was 3.7 % for 54 women given three doses . The mean hospital stay ( 4.5 days ) was similar for both regimens ; for those who developed major infection it was eight days . More aerobic bacteria with altered species dominance and fewer anaerobic bacteria were recovered from the vaginal cuff at discharge from the hospital when compared with those recovered from the endocervix preoperatively . There was a trend toward increasing minimal inhibitory concentrations to cefoxitin in bacteria isolated after surgery , which was more frequent in women given three doses . There was not a statistically significant intergroup difference in the recovery of bacteria resistant to cefoxitin in vitro after surgery . A single preoperative dose of cefoxitin was as effective in preventing major infection as were three perioperative doses , while providing other real and theoretic benefits", "Background A prophylactic antibiotic is recommended to reduce infection-related complication following cesarean delivery . There is a current debate on the time of prophylactic antibiotic in cesarean delivery . Methods An opened r and omized , controlled clinical trial was conducted at Soba hospital , Sudan to investigate the timing ( pre-incision or after clamping of the umbilical cord ) of ceftizoxime for elective cesarean delivery . The outcome measures were ; the incidence of post-cesarean febrile and infection-related morbidity and neonatal outcomes between the two groups . Results Hundred –eighty women ( 90 women in each arm of the study ) received intravenous injection of 1 g of ceftizoxime as single dose either at pre-incision or after clamping of the umbilical cord . None of the women in either group had endometritis . One woman in the pre-incision group had chest infection . There was no significant difference in the incidence of wound infection between the two groups , 8 ( 6.7 % ) vs. 3 ( 3.3 % ) ; P = 0.2 . Two babies in the pre-incision group ( P = 0.497 ) had a low Apgar score ( neonatal jaundice between the two groups , 5 ( 5.5 % ) vs. 4 ( 4.4 % ) , P = 0.2 . There was no perinatal death . Conclusions There was no difference in the two regimens ( pre-incision or post-clamping of the umbilical cord ) of ceftizoxime as prophylactic for elective cesarean delivery . Trial registration", "This study compared Triclosan coated polyglactin 910 ( Vicryl * Plus ) with polyglactin 910 ( Vicryl * ) on abdominal wall healing in colorectal surgery patients . 184 patients with colorectal cancer were included in the study . In 91 , the abdominal wall was closed with the Vicryl * Plus , and in 93 patients with Vicryl. Demographic characteristics , biochemical inflammatory parameters , wound appearance , length of hospital stay , postoperative wound complications and post-incisional hernia were recorded . In the Vicryl Plus group there was a shorter hospital stay ( 13.2 + /- 1.3 days ; 21.4 + /- 2.8 respectively ) . In the Vicryl * Plus group inflammatory parameters decreased to normal within the first week whereas in the Vicryl * group remained increased . In the Vicryl * Plus group four patients had a wound discharge , seven had inflammatory reactions to the skin sutures . One dehiscence was noticed . In the Vicryl * group 12 patients had an SSI , 14 patients had inflammatory reactions to the skin sutures and 7 patients had a wound dehiscence . Closure of the abdominal wall using Vicryl * Plus decreases postoperative wound complications , length of hospital stay and is associated with a more rapid return of inflammatory markers to normal", "BACKGROUND : The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass . METHODS : We design ed a prospect i ve study in a university hospital where 109 consecutive patients were enrolled during a six-month period . All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass . Patients were r and omly allocated into two groups . One group consisted of 55 patients and had a target glucose level of 80–130 mg/dl , while the other contained 54 patients and had a target glucose level of 160–200 mg/dl . These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit . Primary outcomes were clinical outcomes , including time of mechanical ventilation , length of stay in the intensive care unit , infection , hypoglycemia , renal or neurological dysfunction , blood transfusion and length of stay in the hospital . The secondary outcome was a combined end-point ( mortality at 30 days , infection or length of stay in the intensive care unit of more than 3 days ) . A p-value of The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group ( p the duration of mechanical ventilation , length of stay in the intensive care unit , blood transfusion , postoperative infection , hypoglycemic event , neurological dysfunction or 30-day mortality ( p>0.05 ) . CONCLUSIONS : In 109 patients undergoing cardiac surgery with cardiopulmonary bypass , both protocol s of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe , easily achieved and not to differentially affect clinical outcomes", "HYPOTHESIS Use of prophylactic antibiotics in elective colorectal surgery is essential . Although single-dose prophylactic antibiotics are recommended , the efficacy of single-dose cephalosporin without metronidazole and oral antibiotics is not fully proven . We conducted a multicenter , r and omized trial of a single dose vs 3 doses of the second-generation cephalosporin cefmetazole . DESIGN A prospect i ve , r and omized , multicenter trial in patients undergoing elective colorectal surgery . SETTING Seven major hospitals in Japan that offer cancer treatment . PATIENTS Patients with colorectal cancer treated from May 6 , 2004 , to April 25 , 2005 . INTERVENTIONS Patients were r and omized to 1 of 2 groups : a single-dose group given a single dose of cefmetazole just before skin incision and a 3-dose group given 2 additional doses of cefmetazole every 8 hours after the first dose just before skin incision . MAIN OUTCOME MEASURES Incidences of incisional surgical site infection ( SSI ) , organ or space SSI , and all other infectious complications within 30 days after surgery . RESULTS A total of 384 patients were enrolled . Seven patients were excluded because of additional surgery or the inability to tolerate mechanical preparation . The incidence of incisional SSI was higher in the single-dose group ( 27/190 or 14.2 % ) than in the 3-dose group ( 8/187 or 4.3 % ) ( P = .009 ) . Incidences of organ or space SSI and other postoperative infectious diseases did not differ significantly between the 2 groups . In multivariate analysis , antibiotic dose was the only significant factor related to the incidence of incisional SSI . CONCLUSION Three-dose cefmetazole administration is significantly more effective for prevention of incisional SSI than single-dose antibiotic administration . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00292708", "Background : A prospect i ve , r and omized study was conducted to evaluate the efficacy of cefuroxime-impregnated cement in the prevention of deep infection after primary total knee arthroplasties performed without so-called clean-air measures , such as laminar flow and body-exhaust suits . Methods : Three hundred and forty primary total knee arthroplasties were performed with cementless fixation of the femoral component and cement fixation of the patellar and tibial components . The knees were r and omly divided into two groups . In Group 1 ( 178 knees ) , cefuroxime-impregnated cement was used for fixation , whereas in Group 2 ( 162 knees ) , the cement did not contain cefuroxime . There was no significant difference between the two groups regarding demographic variables , the preoperative or postoperative knee score , the duration of the operation or of the use of the tourniquet , or the amount of blood transfused perioperatively . The average duration of follow-up was forty-nine months ( range , twenty-six to eighty months ) . Results : No deep infection developed in the 178 knees in Group 1 , whereas a deep infection developed in five ( 3.1 % ) of the 162 knees in Group 2 ( p = 0.0238 ) . Two superficial wound infections developed in each group . Conclusions : Cefuroxime-impregnated cement was shown to be effective in the prevention of early to intermediate deep infection after primary total knee arthroplasty performed with use of perioperative systemic antibiotic prophylaxis but no so-called clean-air measures", "Background . The purpose of this prospect i ve , r and omized study was to compare the efficacy of single‐dose versus 1‐day cefazolin prophylaxis for the prevention of postoperative gynecologic infections ", "OBJECTIVE : Most postcesarean infections are caused by anaerobic bacteria . Oxidative killing , an important defense against surgical infections , depends on the oxygen level in contaminated tissue . Among patients undergoing colorectal surgery , perioperative supplemental oxygen decreased infection rates by 50 % . We tested the hypothesis that high-concentration inspired oxygen decreases the incidence of surgical site infection in women undergoing cesarean delivery . METHODS : Using a double blind technique , 143 women undergoing cesarean delivery under regional anesthesia after the onset of labor were r and omly assigned to receive low- or high-concentration inspired oxygen via nonrebreathing mask during the operation and for 2 hours after . Surgical site infection was defined clinical ly as administration of antibiotics for postpartum endometritis or wound infection during the initial hospital stay or within 14 days of surgery . Interim statistical analysis was performed after 25 % of the planned sample size ( 143 of 550 ) accrued using intention-to-treat principle . The stopping rule P value for futility was P>.11 with two planned interim analyses . RESULTS : Postcesarean infection occurred in 17 ( 25 % , 95 % confidence interval [ CI ] 15–35 % ) of 69 women assigned to high-concentration oxygen compared with 10 ( 14 % , 95 % CI 6–22 % ) of 74 women assigned to low-concentration inspired oxygen ( relative risk 1.8 , 95 % CI 0.9–3.7 , P=.13 ) . The P value exceeded the P value for futility , suggesting these differences were unlikely to reach statistical significance with continued recruitment . CONCLUSION : High-concentration perioperative oxygen delivered through a nonrebreathing mask did not decrease the risk of postcesarean surgical site infection . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00670020 LEVEL OF EVIDENCE :", "The purpose of this study was to compare a traditional two-step method of preoperative skin preparation using aqueous iodophors with a one-step method using an iodophor-in-alcohol solution . Sixty patients having clean total joint surgery were r and omly divided into two preoperative skin preparation groups ( 30 in each ) . In one group , the skin was prepared with a traditional five-minute aqueous iodophor scrub followed by the application of an aqueous iodophor solution as a paint . In the other group , the skin was prepared with a one-step application of a water-insoluble iodophor-in-alcohol solution applied as a paint . Bacterial colony counts were made by sampling the incision area with culture plates before skin preparation and just prior to wound closure . The one-step application of a water-insoluble iodophor-in-alcohol solution was equally as effective as the traditional scrub- and -paint preparation in reducing the number of bacteria about the operative site . The water-insoluble preparation also result ed in significantly improved drape adhesion as compared to the st and ard scrub- and -paint procedure . The one-step water-insoluble iodophor-in-alcohol solution fulfills the requirements for an operative site skin preparation and significantly improves drape adhesion . It is more convenient , easier to apply , less time consuming , and potentially less expensive than the traditional scrub- and -paint method", "It is customary to administer prophylactic antibiotics before exsanguination of the limb and inflation of a tourniquet in extremity surgery . To compare the clinical outcome in lower limb operations when prophylactic antibiotics were administered before versus after limb exsanguination and tourniquet inflation , we r and omized patients to the administration of prophylactic antibiotics 5 minutes before exsanguination and inflation of the tourniquet ( ABT ) and administration of prophylactic antibiotics 1 minute after inflation of the tourniquet ( AAT ) . A total of 106 patients completed the study , including 76 males ( 71.7 % ) and 30 females ( 28.3 % ) . Of the 106 patients , 54 ( 50.9 % ) received antibiotics before tourniquet inflation ( ABT ) and 52 ( 49.1 % ) after tourniquet inflation ( AAT ) . Most of the operations ( 71.7 % ) involved open reduction and internal fixation of fractures . In the ABT group , 8 wounds ( 14.8 % ) developed postoperative infection . In the AAT group , 2 ( 3.9 % ) developed wound infection ( P = .031 ) . The mean period to wound healing in the ABT group was 4.0 ± 2.3 weeks and was 3.0 ± 0.5 weeks in the AAT group ( P = .002 ) . Overall , 100 % of the patients in the AAT group were satisfied compared with 85.2 % in the ABT group . The difference was statistically significant ( P = .005 ) . The results of our study suggest that administration of prophylactic antibiotics before exsanguination and inflation of a lower extremity tourniquet does not give better results than administration of the antibiotic shortly after inflation of the tourniquet", "In a prospect i ve study of cephalothin prophylaxis for patients who underwent aortocoronary bypass an unacceptably high rate ( 44 % ) of Staphylococcus aureus sternotomy infections occurred in a placebo-treated group . In two other groups of patients , one group given cephalothin intraoperatively and the other given the antibiotic both intra- and postoperatively , such infections occurred with similar frequency ( 2.6 % and 2.1 % respectively ) . This study demonstrates the need for antistaphylococcal agents during aortocoronary bypass operation . No advantage is derived by extending this therapy beyond the operative period", "BACKGROUND Although evidence for the efficacy of postoperative antimicrobial prophylaxis is scarce , many patients routinely receive such treatment after major surgeries . We aim ed to compare the incidence of surgical-site infections with intraoperative antimicrobial prophylaxis alone versus intraoperative plus postoperative administration . METHODS We did a prospect i ve , open-label , phase 3 , r and omised study at seven hospitals in Japan . Patients with gastric cancer that was potentially curable with a distal gastrectomy were r and omly assigned ( 1:1 ) to receive either intraoperative antimicrobial prophylaxis alone ( cefazolin 1 g before the surgical incision and every 3 h as intraoperative supplements ) or extended antimicrobial prophylaxis ( intraoperative administration plus cefazolin 1 g once after closure and twice daily for 2 postoperative days ) . R and omisation was stratified using Pocock and Simon 's minimisation method for institution and American Society of Anesthesiologists scores , and Mersenne twister was used for r and om number generation . The primary endpoint was the incidence of surgical-site infections . We assessed non-inferiority of intraoperative therapy with a margin of 5 % . Analysis was by intention-to-treat . During hospital stay , infection-control personnel assessed patients for infection , and the principal surgeons were required to check for surgical-site infections at outpatient clinics until 30 days after surgery . This study is registered with UMIN-CTR , UMIN000000631 . FINDINGS Between June 2 , 2005 , and Dec 6 , 2007 , 355 patients were r and omly assigned to receive either intraoperative antimicrobial prophylaxis alone ( n=176 ) or extended antimicrobial prophylaxis ( n=179 ) . Eight patients ( 5 % , 95 % CI 2 - 9 % ) had surgical-site infections in the intraoperative group compared with 16 ( 9 % , 5 - 14 ) in the extended group . The relative risk of surgical-site infections with intraoperative antimicrobial prophylaxis was 0·51 ( 0·22 - 1·16 ) , which revealed statistically significant non-inferiority ( p<0·0001 ) . INTERPRETATION Elimination of postoperative antimicrobial prophylaxis did not increase the incidence of surgical-site infections after a gastrectomy . Therefore , this treatment is not recommended after gastric cancer surgery", "A total of 169 patients undergoing colorectal surgery were r and omly allocated to receive either gentamicin plus metronidazole or oral ciprofloxacin plus metronidazole as prophylaxis ; they were also allocated to receive cover for 1 or 3 days . Twenty‐eight patients ( 17 per cent ) developed postoperative wound infections . The proportion of patients with wound infections and other infective complications was significantly less ( P advantages in efficacy and ease of administration compared with parenteral antibiotics", "To investigate the usefulness of a st and ard surgical preparation in prevention of surgical site contamination , 49 consecutive patients undergoing foot or ankle surgery were r and omly assigned to st and ard preparation with chlorhexidine gluconate home scrubs and preoperative povidone-iodine or to st and ard preparation plus preoperative preparation with 70 % alcohol . Results were available for all 49 patients . Cultures were positive for normal aerobic bacteria from the toes of nine of 26 patients ( 35 % ) receiving st and ard surgical preparation and from the toes of 13 of 23 patients ( 57 % ) receiving st and ard preparation plus alcohol ( P=0.12 ) . No patient had a positive culture for anaerobic organisms or clinical evidence of infection or wound problems . St and ard surgical preparation did not provide a completely sterile field , and the inclusion of alcohol added no benefit", "OBJECTIVE To compare the proportion of early postoperative infection in clean orthopedic surgery after single dose of prophylactic antibiotic and multiple doses of prophylactic antibiotic . DESIGN Interventional quasi-experimental study . PLACE AND DURATION OF STUDY Department of Orthopedics , Abbasi Shaheed Hospital , Karachi from April 2004 to March 2005 . MATERIAL AND METHODS Two hundred patients of either age and gender , undergoing clean orthopedic surgery were equally divided into two groups A and B. Group A was given single dose of prophylactic antibiotic , while group B was given multiple doses of prophylactic antibiotic . Follow-up period was 28 days . All cases were evaluated for postoperative wound infection . Sampling technique was non-probability convenience . RESULTS Mean age was 35.51+/-20.79 years in group A and 26.17+/-19.79 years in group B. However , there was a significantly higher proportion of male patients in group B than in group A ( p=0.006 ) . Statistical analysis showed no significant difference in the proportion of early postoperative infection cases between the two groups(p=0.270 ) . Staphylococcus aureus was the commonest organism cultured from the wound discharge in our study followed by E. coli . Eight of our cases having postoperative wound infection showed no growth , out of which 7 were superficial and 1 was deep . There was no significant difference between the two groups regarding mean operating time and duration of stay in hospital . CONCLUSION There was no statistically significant difference in the proportion of early postoperative infection cases between the two groups", "BACKGROUND Deep sternal wound infections ( DSWI ) remain a devastating complication in cardiac surgery applying full sternotomy . As the risk profile in cardiac surgery changed toward an older and sicker population , the incidence of DSWI increases . Platelet rich plasma ( PRP ) holds promise in tissue regeneration with respect to bone regeneration , reduction of bleeding , and accelerated wound healing . The effect of PRP on DSWI was investigated in high-risk patients undergoing cardiac surgery with full sternotomy . METHODS 196 consecutive patients at risk of DSWI were r and omized to application of autologous PRP before sternal wiring ( n = 97 ) or control ( n = 99 ) . All patients underwent cardiac surgery on cardiopulmonary bypass with cardioplegic cardiac arrest . Endpoint was occurrence of DSWI requiring revision surgery . RESULTS Demographic , intraoperative , and perioperative variables as well as risk factors were comparable between groups . Incidence of DSWI was not different between the PRP-group and the control-group ( 6/97 ( 6.2 % ) vs. 3/99 ( 3.0 % ) ; n.s . ) . CONCLUSIONS Local application of autologous PRP in cardiac surgery patients with full sternotomy at high risk for sternal complications did not reduce the incidence of DSWI", "BACKGROUND Coated polyglactin 910 suture with triclosan was developed recently in order to imbue the parent suture , coated polyglactin 910 , with antibacterial activity against the most common organisms that cause surgical site infections ( SSI ) . Because such alterations could alter the physical properties of the suture , this study sought to compare the intraoperative h and ling and wound healing characteristics of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture in pediatric patients undergoing various general surgical procedures . METHODS This was a prospect i ve , r and omized , controlled , open-label , comparative , single-center study . Pediatric patients ( age 1 - 18 years ) undergoing various surgical procedures were r and omized in a 2:1 ratio to treatment with either coated polyglactin 910 suture with triclosan or coated polyglactin 910 suture . The primary endpoint was the surgeon 's assessment of the overall intraoperative h and ling of coated polyglactin 910 suture with triclosan and traditional coated polyglactin 910 suture without triclosan . The secondary endpoints included specific intraoperative suture h and ling measures and wound healing assessment s. The suture h and ling measures were ( 1 ) ease of passage through tissue ; ( 2 ) first-throw knot holding ; ( 3 ) knot tie-down smoothness ; ( 4 ) knot security ; ( 5 ) surgical h and ling ; ( 6 ) surgical h and ; ( 7 ) memory ; and ( 8) suture fraying . Assessment of wound healing included the following : Healing progress , infection , edema , erythema , skin temperature , seroma , suture sinus , and pain . Adverse events were recorded . RESULTS Scores for intraoperative h and ling were favorable and not significantly different for both sutures , although coated polyglactin 910 suture with triclosan received more \" excellent \" scores ( 71 % vs. 59 % ) . Wound healing characteristics were comparable for both sutures except for pain on postoperative day 1 . Significantly fewer patients treated with polyglactin 910 suture with triclosan reported pain on day 1 than patients who received the other suture ( 68 % vs. 89 % , p = 0.01 ) . The overall incidence of adverse events was 18 % ; none was devicerelated . CONCLUSIONS Coated polyglactin 910 suture with triclosan performed as well or better than traditional coated polyglactin 910 suture in pediatric patients undergoing general surgical procedures . The incidence of postoperative pain was significantly less in patients treated with coated polyglactin 910 suture with triclosan than the traditional suture . We speculate that polyglactin 910 suture with triclosan , by inhibiting bacterial colonization of the suture , reduced pain that can be an indicator of \" sub clinical \" infection . Coated polyglactin 910 suture with triclosan may be a useful alternative in patients at increased risk of developing SSI", "The purpose of this study was to determine the effects of 28 % oxygen given in the first 36 hours after surgery on tissue oxygen , collagen deposition , and clinical healing outcomes . Twenty-four subjects having cervical spine surgical procedures participated in a r and omized , repeated- measures pilot study of tissue and healing effects of postoperative supplemental oxygen . The treatment group ( n = 13 ) received 28 % oxygen for the first 36 postoperative hours , whereas the control group ( n = 11 ) was maintained on room air . Subcutaneous tissue oxygen and temperature were measured at intervals up to 36 hours postsurgery . Wound healing was evaluated by hydroxyproline content in a subcutaneous polytetrafluoroethylene tube removed on the 7th postoperative day . Clinical outcomes were evaluated for the 30 days post – hospital discharge . Subjects in the treatment group had significantly higher tissue oxygen tension overall , and at postoperative hours 1 , 2 , 18 , and 36 , with mean values 10 to 20 mm Hg higher than control subjects . Significant differences were not found in hydroxyproline levels or clinical wound outcome measures . Low level , short duration , supplemental oxygen increased and sustained wound tissue oxygen and was well tolerated by subjects . Larger studies of population s at risk for wound complications are needed to investigate variables of dose and duration of oxygen therapy in relation to clinical and cellular wound healing outcomes", "BACKGROUND In colorectal surgeries , surgical site infections ( SSIs ) frequently cause morbidity ; an incidence of up to 20 % has been shown in previous studies . Recently , to prevent microbial colonization of suture material in operative wounds , triclosan-coated polyglactin suture material s with antimicrobial activity have been developed ; however , their significance in colorectal surgery remains unclear . This r and omized controlled trial was conducted to assess the value of triclosan-coated polyglactin sutures in colorectal surgery . METHODS A total of 410 consecutive patients who had undergone elective colorectal operations were enrolled in this trial . Of those patients , the 206 in the study group underwent wound closure with triclosan-coated polyglactin 910 antimicrobial sutures , and the 204 patients in the control group received conventional wound closures with polyglactin 910 sutures . RESULTS The study group and the control group were comparable regarding risk factors for SSIs . The incidence of wound infection in the study group was 9 of 206 patients ( 4.3 % ) , and that in the control group was 19 of 204 patients ( 9.3 % ) . The difference is statistically significant in the 2 groups ( P = .047 ) . The median additional cost of wound infection management was $ 2,310 . The actual entire additional cost , therefore , of 9 patients in the study group was $ 18,370 , and that of 19 patients in the control group was $ 60,814 . CONCLUSION Triclosan-coated sutures can reduce the incidence of wound infections and the costs in colorectal surgery", "Feet are prone to bacterial contamination . We hypothesized that chlorhexidine scrub and isopropyl alcohol paint provide superior local flora reduction than povidone-iodine scrub and paint . Patients with intact , uninfected skin having clean elective foot and ankle surgery were prospect ively enrolled and r and omly assigned to skin preparation with povidone-iodine ( Group 1 ) or chlorhexidine scrub and isopropyl alcohol paint ( Group 2 ) . Culture swabs ( aerobic , anaerobic , acid fast , fungus , and routine antibiotic sensitivity ) were taken from all web spaces , nail folds , toe surfaces , and proposed surgical incision sites . One-hundred twenty-seven patients were enrolled ( mean age , 46 years ; range , 16–85 years ) . Sixty-seven patients were assigned to Group 1 ; 60 patients were assigned to Group 2 . In Group 1 , 53 of 67 patients ( 79 % ) had positive cultures ; in Group 2 , 23 of 60 patients ( 38 % ) had positive cultures . These data indicate that chlorhexidine and alcohol provide better reduction in bacterial carriage than povidone-iodine . Based on these data , we recommended chlorhexidine as the surgical preparatory agent for the foot and ankle . Level of Evidence : Therapeutic study , Level I-1a ( significant difference ) . See the Guidelines for Authors for a complete description of levels of evidence", "OBJECTIVE Surgical site infection is a major cause of mortality and morbidity . We have explored the use of a microbial sealant applied before the surgical incision to reduce surgical site infection . METHODS We conducted a prospect i ve , r and omized , controlled clinical trial to determine the efficacy of a cyanoacrylate sealant in patients undergoing coronary artery bypass grafting . Both left and right long saphenous veins were harvested in individual patients below the knee if 3 or more lengths of vein were required . The sealant ( Kimberly-Clark InteguSeal , Roswell , Ga ) was applied to 1 leg chosen r and omly , and the other leg was prepared in a conventional fashion . Microbiological swabs from the leg wounds were taken at 5 days , and wounds were assessed according to the Southampton score at 30 days by 2 blinded observers . RESULTS The baseline characteristics of the treated and untreated legs were similar because the procedure was conducted on each individual patient . The study was terminated at 47 patients after review . Patients in whom the sealant was used had 1 ( 2.1 % ) wound infection , and there were 12 ( 25.5 % ) wound infections in the conventionally prepared leg ( P = .001 ) . There were 13 positive cultures from the treated leg and 22 positive cultures from the untreated site . CONCLUSIONS The microbial skin sealant applied immediately before the incision significantly reduced the rate of surgical site infection . There was no sensitivity or adverse reaction after application . The treatment was easily integrated with existing routine preoperative procedures . Microbial sealant may thus be a useful addition to a multimodal approach to minimize surgical site infection", "Background Surgical wound infection ( SWI ) is a common complication after peripheral vascular surgery . In a prospect i ve study , triclosan-coated sutures were reported to decrease the incidence of surgical site infection after various surgical procedures . The aim of our study was to test the hypothesis that use of triclosan-coated sutures decreases the incidence of SWI after lower limb vascular surgery . Methods This prospect i ve , r and omized , multicenter , double-blinded trial was conducted between July 2010 and January 2011 in five hospitals in Finl and . We r and omly allocated 276 patients undergoing lower limb revascularization surgery to a study ( n = 139 ) or a control ( n = 137 ) group . Surgical wounds in the study group were closed with triclosan-coated suture material , and wounds in the control group were closed with noncoated sutures . The main outcome measure was SWI . A surgical wound complication was considered to be an infection if there were bacteria isolated from the wound or if there were areas of localized redness , heat , swelling , and pain around the wound appearing within 30 days after the operative procedure . Logistic regression analysis was used to assess the independent effect of triclosan-coated sutures on the incidence of SWI . Results Altogether , 61 ( 22.1 % ) patients developed SWI . SWI occurred in 31 ( 22.3 % ) patients in the study group and in 30 ( 21.9 % ) patients in the control group ( odds ratio 1.10 , 95 % confidence interval 0.61–2.01 , p = 0.75 . ) Conclusions The use of triclosan-coated sutures does not reduce the incidence of SWI after lower limb vascular surgery", "OBJECTIVE : To evaluate whether supplemental perioperative oxygen decreases surgical site wound infections or endometritis . STUDY DESIGN : This was a prospect i ve , r and omized trial . Patients who were to undergo cesarean delivery were recruited and r and omly allocated to either 30 % or 80 % oxygen during the cesarean delivery and for 1 hour after surgery . The obstetricians and patients were blinded to the concentration of oxygen used . Patients were evaluated for wound infection or endometritis during their hospital stay and by 6 weeks postpartum . The primary end point was a composite of either surgical site infection or endometritis . RESULTS : Eight hundred thirty-one patients were recruited . Of these , 415 participants received 30 % oxygen perioperatively and 416 received 80 % oxygen . The groups were well matched for age , race , parity , diabetes , number of previous cesarean deliveries , and scheduled compared with unscheduled cesarean deliveries . An intention-to-treat analysis was used . There was no difference in the primary composite outcome ( 8.2 % in women who received 30 % oxygen compared with 8.2 % in women who received 80 % oxygen , P=.89 ) , no difference in surgical site infection in the two groups ( 5.5 % compared with 5.8 % , P=.98 ) , and no significant difference in endometritis in the two groups ( 2.7 % compared with 2.4 % , P=.66 ) , respectively . CONCLUSION : Women who received 80 % supplemental oxygen perioperatively did not have a lower rate of a surgical site infection or endometritis as compared with women who received 30 % supplemental oxygen concentration . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www.clincaltrials.gov , NCT00876005 . LEVEL OF EVIDENCE :", "OBJECTIVES Although the usefulness of antimicrobial prophylaxis for clean-contaminated surgery has been recognized , only a few r and omized controlled studies on the duration of administration after hepatectomy have been performed . We investigated the duration of antimicrobial prophylaxis after hepatectomy . METHODS The subjects were 180 patients who underwent hepatectomy without reconstruction of the biliary or intestinal tract between April 2003 and March 2006 at our department . The patients were r and omly allocated to groups to be treated with flomoxef sodium as antimicrobial prophylaxis for 2 days ( 89 patients ) or 5 days ( 91 patients ) , including the operation day . The presence or absence of systemic inflammatory response syndrome ( SIRS ) and infections was investigated . RESULTS No significant differences were noted in patient background between the two groups . Infections occurred in seven and six patients in the 2 day and 5 day treatment groups ( 7.9 % and 6.6 % ) , respectively , showing no significant difference between the two groups . No significant difference was noted when the cases were divided into surgical site infections and remote infections . The positive rate of SIRS was significantly higher in the 2 day treatment group than in the 5 day treatment group on days 2 and 3 after surgery . The risk factors in patients who developed infections were blood loss , operation time and the complication of biliary fistula . CONCLUSIONS Two day administration of flomoxef sodium may be sufficient for antimicrobial prophylaxis after hepatectomy . However , when SIRS is positive on post-operative day 2 , and induction of liver failure is of concern , it may be safer to continue antimicrobial drug administration until SIRS is eliminated", "BACKGROUND Twenty-four hours of perioperative antibiotics provides effective prophylaxis for most head and neck cancer resections . Many reconstructive surgeons have been hesitant to apply this st and ard to free-flap reconstruction of the head and neck . This prospect i ve clinical trial compared short-course and long-course clindamycin prophylaxis for wound infection in patients with head and neck cancer undergoing free-flap reconstruction . METHODS Seventy-four patients were r and omized to receive short-course ( 3 doses ) or long-course ( 15 doses ) clindamycin perioperatively . Wound infections , fistulas , and other postoperative complications were documented by faculty surgeons who were blinded as to treatment group . RESULTS The differences in wound infections and other complications were statistically insignificant . No other independent predictors of wound complications emerged in this series of patients . CONCLUSIONS Short-course clindamycin is as effective as long-course clindamycin in preventing wound infections after free-flap surgery for head and neck ablative defects", "The aim of this study was to investigate whether an extended course of prophylactic antibiotic could reduce the wound infection rate in a subtropical country . Fifty-three consecutive cases scheduled to receive major head and neck operations were r and omised into one-day or three-day prophylactic antibiotic groups . Thirteen cases ( 24.5 per cent ) developed wound infections after operations . The duration of prophylactic antibiotic was not related to the surgical wound infection . However , pre-operative haemoglobulin less than 10.5 g/dl ( odds ratio : 7.24 , 95 per cent confidence interval : 1.28 - 41.0 ) and reconstruction with a free flap or pectoris major myocutaneous flap during the operation ( odds ratio : 11.04 , 95 per cent confidence interval : 1.17 - 104.7 ) were associated factors significantly influencing post-operative wound infection . Therefore , one day of prophylactic antibiotic was effective in major head and neck procedures but should not be substituted for proper aseptic and meticulous surgical techniques", "CONTEXT Supplemental perioperative oxygen has been variously reported to halve or double the risk of surgical wound infection . OBJECTIVE To test the hypothesis that supplemental oxygen reduces infection risk in patients following colorectal surgery . DESIGN , SETTING , AND PATIENTS A double-blind , r and omized controlled trial of 300 patients aged 18 to 80 years who underwent elective colorectal surgery in 14 Spanish hospitals from March 1 , 2003 , to October 31 , 2004 . Wound infections were diagnosed by blinded investigators using Centers for Disease Control and Prevention criteria . Baseline patient characteristics , anesthetic treatment , and potential confounding factors were recorded . INTERVENTIONS Patients were r and omly assigned to either 30 % or 80 % fraction of inspired oxygen ( FIO2 ) intraoperatively and for 6 hours after surgery . Anesthetic treatment and antibiotic administration were st and ardized . MAIN OUTCOME MEASURES Any surgical site infection ( SSI ) ; secondary outcomes included return of bowel function and ability to tolerate solid food , ambulation , suture removal , and duration of hospitalization . RESULTS A total of 143 patients received 30 % perioperative oxygen and 148 received 80 % perioperative oxygen . Surgical site infection occurred in 35 patients ( 24.4 % ) administered 30 % FIO2 and in 22 patients ( 14.9 % ) administered 80 % FIO2 ( P=.04 ) . The risk of SSI was 39 % lower in the 80 % FIO2 group ( relative risk [ RR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.38 - 0.98 ) vs the 30 % FIO2 group . After adjustment for important covariates , the RR of infection in patients administered supplemental oxygen was 0.46 ( 95 % CI , 0.22 - 0.95 ; P = .04 ) . None of the secondary outcomes varied significantly between the 2 treatment groups . CONCLUSIONS Patients receiving supplemental inspired oxygen had a significant reduction in the risk of wound infection . Supplemental oxygen appears to be an effective intervention to reduce SSI in patients undergoing colon or rectal surgery . Trial Registration Clinical Trials.gov Identifier : NCT00235456", "BACKGROUND Wound infection after clean surgery is an expensive and often underestimated cause of patient morbidity , and the benefits of using prophylactic antibiotics have not been proven . Warming patients during colorectal surgery has been shown to reduce infection rates . We aim ed to assess whether warming patients before short duration , clean surgery would have the same effect . METHODS 421 patients having clean ( breast , varicose vein , or hernia ) surgery were r and omly assigned to either a non-warmed ( st and ard ) group or one of two warmed groups ( local and systemic ) . We applied warming for at least 30 min before surgery . Patients were followed up and masked outcome assessment s made at 2 and 6 weeks . FINDINGS Analysis was done on an intention-to-treat basis . We identified 19 wound infections in 139 non-warmed patients ( 14 % ) but only 13 in 277 who received warming ( 5 % ; p=0.001 ) . Wound scores were also significantly lower ( p=0.007 ) in warmed patients . There was no significant difference in the development of haematomas or seromas after surgery but the non-warmed group were prescribed significantly more postoperative antibiotics ( p=0.002 ) . INTERPRETATION Warming patients before clean surgery seems to aid the prevention of postoperative wound infection . If applied according to the manufacturers guidelines these therapies have no known side-effects and might , with the support of further studies , provide an alternative to prophylactic antibiotics in this type of surgery", " A series of 921 operations was studied . R and om cases were treated by preliminary application of a plastic adhesive drape , the remainder being controls . No significant difference was observed in the rate of wound infection between the two groups", "BACKGROUND This study was design ed to obtain data on the incidence of postoperative infection in patients undergoing elective orthopedic surgery and receiving white blood cell (WBC)-filtered blood components prepared according to current st and ards . STUDY DESIGN AND METHODS A total of 308 consecutive orthopedic patients who opted for preoperative autologous blood donation ( PAD ) for primary unilateral hip and knee replacement surgery were enrolled in a prospect i ve observational study of the incidence of postoperative infection . Patients with contraindications for PAD or with any infectious disease were not included in the study . To identify probably confounding factors , differences between patient groups were analyzed first . Identified factors , which differed between groups , and variables describing blood supply were further tested in uni- and multivariate logistic regression analysis for their independent influence on development of postoperative infection . Infection rates were compared on the basis of actual transfusion groups . RESULTS Of the 308 study patients , 101 were not transfused , 85 received their PAD , 100 received allogeneic WBC-filtered red blood cells ( RBCs ) , and 22 were given autologous RBCs and additionally allogeneic WBC-filtered RBCs . Overall the infection rate was 6.82 percent ( 21/308 ) . Infection rates varied significantly between transfusion groups ( no transfusion , 6.9 % ; autologous RBCs , 1.2 % ; allogeneic WBC-filtered RBCs , 12.0 % ; both transfusion types , 4.6 % ; p = 0.03 ) . Allogeneic recipients showed significantly more infections compared to autologous recipients ( p = 0.0053 ) . Multivariate regression analysis confirmed transfusion of allogeneic WBC-filtered RBCs as an independent variable predicting postoperative infection ( odds ratio , 23.65 ; confidence interval , 1.3 - 422.1 ; p = 0.01 ) . CONCLUSION Differences in postoperative infection rates between allogeneic and autologous recipients are still observable , although universal WBC filtration has been introduced into clinical practice", "Whether or not topical application of ampicillin is necessary in patients undergoing elective colorectal operations was investigated . After mechanical preparation , 193 patients received 2 grams of cefotaxime administered intravenously from the start of the operation ; patients received two more doses within the next 12 hours . In addition , patients were r and omized to receive or not receive prophylaxis against infection of 2 grams of ampicillin in the site of the incision at closure . Twenty-three patients did not complete the study . Wound infection occurred in five of 81 patients who had topical application of ampicillin compared with six of 89 patients who did not receive prophylaxis ; the difference was not significant . There were no significant differences in rates of wound dehiscence , intra-abdominal abscess or anastomotic leakage . Escherichia coli and Bacteroides fragilis were the predominant microorganisms isolated . Thus , topical application of ampicillin did not lower the wound infection rate when there was a preoperative antibiotic administered intravenously", "BACKGROUND Antiseptic preoperative skin site preparation is used to prepare the operative site before making a surgical incision . The goal of this preparation is a reduction in postoperative wound infection . The most straightforward technique necessary to achieve this goal remains controversial . STUDY DESIGN A prospect i ve r and omized trial was design ed to prove equivalency for two commonly used techniques of surgical skin site preparation . Two hundred thirty-four patients undergoing nonlaparoscopic abdominal operations were consented for the trial . Exclusion criteria included presence of active infection at the time of operation , neutropenia , history of skin reaction to iodine , or anticipated insertion of prosthetic material at the time of operation . Patients were r and omized to receive either a vigorous 5-minute scrub with povidone-iodine soap , followed by absorption with a sterile towel , and a paint with aqueous povidone-iodine or surgical site preparation with a povidone-iodine paint only . The primary end point of the study was wound infection rate at 30 days , defined as presence of clinical signs of infection requiring therapeutic intervention . RESULTS Patients r and omized to the scrub- and -paint arm ( n = 115 ) and the paint-only arm ( n = 119 ) matched at baseline with respect to age , comorbidity , wound classification , mean operative time , placement of drains , prophylactic antibiotic use , and surgical procedure ( all p > 0.09 ) . Wound infection occurred in 12 ( 10 % ) scrub- and -paint patients , and 12 ( 10 % ) paint-only patients . Based on our predefined equivalency parameters , we conclude equivalence of infection rates between the two preparations . CONCLUSIONS Preoperative preparation of the abdomen with a scrub with povidone-iodine soap followed by a paint with aqueous povidone-iodine can be ab and oned in favor of a paint with aqueous povidone-iodine alone . This change will result in reductions in operative times and costs", "Sternal or mediastinal infection after heart operations occurs infrequently but carries a high cost in money , morbidity , and mortality . At our hospital , Staphylococcus nonaureus causes most of these infections and is uniformly sensitive to vancomycin . In a prospect i ve study of 416 patients having cardiac operations , r and omized by hospital record number , topical vancomycin was applied to the cut sternal edges in 223 patients ( group V ) and was omitted in the control group ( C ) of 193 patients . The vancomycin was applied in a hemostatic paste of topical thrombin and powdered absorbable gelatin ; in the control group only the hemostatic paste was applied . All patients received prophylactic systemic antibiotics for 2 days . Sternal infection occurred in one patient in group V ( 0.45 % ) and in seven patients in group C ( 3.6 % ) ( p = 0.02 ) . Infection also correlated with longer operative times ( p = 0.027 ) . By multivariate testing , vancomycin ( p = 0.013 ) and shorter operative times ( p = 0.014 ) independently predicted reduced infection rates . In the one patient with an infection in group V , Staphylococcus aureus was cultured ; this organism was also cultured in two patients in group C , with Staphylococcus nonaureus being the culprit in the other five patients with sternal infections in group C. Topical vancomycin applied to the cut sternal edges reduces the risk of postoperative sternal infection", "The ideal prophylactic antibiotic regimen has not been established for patients undergoing colectomy , mucosal proctectomy , and endorectal ileoanal anastomosis , a prolonged operation frequently accompanied by abdominal and pelvic contamination and associated with an infection rate up to 20 % . The aim of this study was to evaluate , in a prospect i ve , r and omized , double-blind fashion , the efficacy of a short perioperative course compared to an extended postoperative course of intravenous antibiotics ( cefoxitin ) in patients undergoing colectomy with ileoanal anastomosis . Forty patients with ulcerative colitis or familial polyposis coli received a mechanical and oral antibiotic bowel preparation and a st and ard three-dose perioperative course of intravenous cefoxitin . Patients then were r and omized to receive intravenous cefoxitin , 1 g every 6 hours , or placebo for 5 days . No differences in overall postoperative morbidity were observed and neither group developed intra-abdominal , pelvic , or wound infections . It is concluded that a st and ard three-dose perioperative course of intravenous antibiotics provides adequate prophylaxis in the prevention of infectious complications in patients undergoing colectomy , mucosal proctectomy , and ileoanal anastomosis", "In a r and omized controlled study of 411 patients undergoing elective colorectal surgery , the efficacy and safety of two different regimens of imipenem were compared with those of a control regimen of cefuroxime plus metronidazole . Surgical infections occurred in 92 ( 26·4 per cent ) of 349 evaluable patients . There were no major differences between the three treatment groups . It is concluded that imipenem is as effective as cefuroxime plus metronidazole in the prevention of sepsis after elective colorectal procedures", "In a study of 60 patients undergoing elective colonic surgery peri-operative infection prophylaxis by the \" one-shot ' method was compared with that of 48-hour duration . The antibacterial agents used were ornidazole and gentamicin . Considering the patient population as a whole , no significant differences were found in the results . All the infectious complications which occurred post-operatively were due to bacterial contamination by aerobic pathogens . No anaerobic pathogens were detected in any of the cases", "Many surgeons apply povidone-iodine ( PVP-I ) to the skin around an incision before closing a wound to reduce wound infection rates . However , the effectiveness of this procedure has not been proven . Forty-seven cases of gastric surgery and 60 cases of colorectal surgery performed at Kanto Medical Center between July 2004 and December 2004 were r and omly assigned to the group with PVP-I or the group without PVP-I. Wound infection and surgical site infection ( SSI ) rates were compared between these two groups . Applying PVP-I was effective in eliminating skin contamination , as cultures became negative in all cases after applying PVP-I. However , this study could not demonstrate the reduction of wound infection or SSI in the group with PVP-I , possibly because the number of cases in this study was too small to make a difference . Subcutaneous tissue contamination was considered a more important factor than skin contamination in causing wound infection", "Five hundred patients undergoing a variety of general surgical operative procedures were prospect ively r and omly allocated into a treatment group , in which the incisions were irrigated with povidone-iodine solution prior to skin closure or into a control group in which wounds were irrigated with saline solution . Wounds were classified according to the degree of bacterial contamination as clean , potentially contaminated , contaminated or dirty . For all categories of surgical incisions , povidone-iodine irrigation result ed in a significant decrease in wound infections over that for saline solution irrigation . Over-all incidence of wound sepsis in the treatment group was seven of 242 patients , 2.9 per cent , compared with the control rate of 39 wound infections of 258 patients , 15.1 per cent -- p less than 0.001", "BACKGROUND There is no clinical trial analyzing the best moment to infuse an antibiotic during knee arthroplasty performed during ischemia . We design ed a single-center , r and omized , double-blind , placebo-controlled trial to evaluate whether antibiotic therapy should be administered before tourniquet inflation or just before tourniquet deflation . MATERIAL AND METHODS Patients who underwent a primary knee arthroplasty were r and omized to receive ( 1 ) 1.5 g of cefuroxime 10 - 30 min before inflation of the tourniquet and placebo 10 min before release of the tourniquet ( st and ard arm ) or ( 2 ) placebo 10 - 30 min before inflation of the tourniquet and 1.5 g of cefuroxime 10 min before release of the tourniquet ( experimental arm ) . In both arms , a postoperative dose of 1.5 g of cefuroxime was given 6 h after the surgical procedure . The main variables associated with the rate of deep-tissue infection after 3 and 12 months of follow-up were gathered . Continuous variables were compared using Student 's t test , and categorical variables were compared using the chi(2 ) test or Fisher 's exact test . RESULTS From September 2004 through December 2005 , a total of 908 patients were r and omized , 442 and 466 of whom were allocated to the st and ard and experimental arms , respectively . There were no differences between treatment arms in terms of age , sex , comorbidity , American Society of Anaesthesiologists score , duration of surgery , need of blood transfusion , or fourth-day hematocrit . The rates of deep-tissue infection among the st and ard and experimental groups were 3.4 % and 1.9 % , respectively , at 3 months of follow-up ( P = .21 ) and 3.6 % and 2.6 % , respectively , at 12 months of follow-up ( P = .44 ) . CONCLUSION The administration of prophylactic antibiotics just before tourniquet release was not inferior to st and ard antibiotic prophylaxis", "A total of 249 patients , undergoing appendectomy for acute appendicitis , were prospect ively r and omized into two groups . Group I , comprising 132 patients , received sterile normal saline irrigation to the surgical wound at closure . Alternatively , Group II included 117 patients , who received intraoperative topical ampicillin irrigation of the wound . Both groups were comparable with regard to age , sex , duration of symptoms , and severity of appendicitis . All patients additionally received preoperative systemic gentamicin and Flagyl . Wound infection occurred in 5.3 % of Group I compared to only 0.9 % of Group II ( P reduction in infection rate was significant ( P ampicillin to systemic gentamicin and Flagyl augments prophylaxis against wound infection in acute appendicitis", "BACKGROUND Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty ; oral regimens could enable shorter hospital stays . We aim ed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty . METHODS In a r and omised , double-blind , phase III study , 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily , beginning 6 - 8 h after surgery , or subcutaneous enoxaparin 30 mg every 12 h , starting 12 - 24 h after surgery . Patients had m and atory bilateral venography between days 11 and 15 . The primary efficacy outcome was the composite of any deep-vein thrombosis , non-fatal pulmonary embolism , or death from any cause up to day 17 after surgery . Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per- protocol population ( absolute non-inferiority limit -4 % ) ; if non-inferiority was shown , we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population . The primary safety outcome was major bleeding . This trial is registered with Clinical Trials.gov , number NCT00362232 . FINDINGS The primary efficacy outcome occurred in 67 ( 6.9 % ) of 965 patients given rivaroxaban and in 97 ( 10.1 % ) of 959 given enoxaparin ( absolute risk reduction 3.19 % , 95 % CI 0.71 - 5.67 ; p=0.0118 ) . Ten ( 0.7 % ) of 1526 patients given rivaroxaban and four ( 0.3 % ) of 1508 given enoxaparin had major bleeding ( p=0.1096 ) . INTERPRETATION Oral rivaroxaban 10 mg once daily for 10 - 14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty . FUNDING Bayer Schering Pharma AG , Johnson & Johnson Pharmaceutical Research & Development", "BACKGROUND We investigated the efficacy of rivaroxaban , an orally active direct factor Xa inhibitor , in preventing venous thrombosis after total knee arthroplasty . METHODS In this r and omized , double-blind trial , 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban , 10 mg once daily , beginning 6 to 8 hours after surgery , or subcutaneous enoxaparin , 40 mg once daily , beginning 12 hours before surgery . The primary efficacy outcome was the composite of any deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause within 13 to 17 days after surgery . Secondary efficacy outcomes included major venous thromboembolism ( i.e. , proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death related to venous thromboembolism ) and symptomatic venous thromboembolism . The primary safety outcome was major bleeding . RESULTS The primary efficacy outcome occurred in 79 of 824 patients ( 9.6 % ) who received rivaroxaban and in 166 of 878 ( 18.9 % ) who received enoxaparin ( absolute risk reduction , 9.2 % ; 95 % confidence interval [ CI ] , 5.9 to 12.4 ; P Major venous thromboembolism occurred in 9 of 908 patients ( 1.0 % ) given rivaroxaban and 24 of 925 ( 2.6 % ) given enoxaparin ( absolute risk reduction , 1.6 % ; 95 % CI , 0.4 to 2.8 ; P=0.01 ) . Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin ( P=0.005 ) . Major bleeding occurred in 0.6 % of patients in the rivaroxaban group and 0.5 % of patients in the enoxaparin group . The incidence of drug-related adverse events , mainly gastrointestinal , was 12.0 % in the rivaroxaban group and 13.0 % in the enoxaparin group . CONCLUSIONS Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty , with similar rates of bleeding . ( Clinical Trials.gov number , NCT00361894 .", "BACKGROUND The effectiveness of topical antibiotics has been shown well enough in vitro to justify strong consideration of their use in orthopaedic procedures . We carried out a r and omised prospect i ve trial to study the role of topical chloramphenicol ointment application on postoperative wounds following surgeries for hip fractures . METHODS One hundred cases with fracture neck of femur were enrolled in the study . They were r and omized into two treatment groups : one group had chloramphenicol ointment applied at the surgical site at the end of procedure and 3rd day postoperatively , while the control group did not . The wound was checked on the 3rd , 6th , 12th and 30th days postoperatively , by a tissue viability nurse on the guidelines issued by the Scottish Centre for Infection and Environmental Health ( SCIEH ) . RESULTS We had 12 cases with superficial infection of which 8 belonged to control group . The risk of developing wound infection , however , was not significant with and without the use of chloramphenicol ointment ( relative risk 0.430 , 95 % confidence interval ( CI ) 0.120 - 1.544 ) . Using multivariate analysis , no association was found between wound infection and age , gender , type of fracture or type of surgical procedure . Smoking was found to be the only factor significantly associated with infection , with the relative risk for current smokers compared with former/non-smokers being 7.29 ( 95 % CI 1.62 - 32.67 ) . CONCLUSION Awareness is needed amongst the general public about the ill effects of smoking . There was reduction in the incidence of wound infection with the use of topical antibiotic ointment . However , this was not statistically significant to recommend its use in routine practice . A larger study should provide useful information on the role of topical antibiotic and its effect on postoperative wound infection", "Pathogenic organisms are frequently present on the skin of vascular patients and are a risk factor for postoperative infection . A r and omised trial of preoperative antiseptic baths was performed in 64 high risk vascular patients to determine whether two chlorhexidine baths could reduce the incidence of postoperative sepsis . Although pathogenic organisms were isolated preoperatively in 35 % of patients , the wound infection rate after chlorhexidine baths ( 26 % ) was greater , though not significantly , than after baths with non-medicated soap ( 11 % ) . An alternative theory that infection arises via lymphatics in the limb was not confirmed when organisms could not be isolated from groin lymph nodes in a group of 35 patients . The case for preoperative antiseptic regimes in vascular surgery remains unproven", "One hundred and twenty patients with acute hip fractures treated operatively were r and omized into two groups . In the ' drape ' group ( n = 65 ) the operation site was covered with plastic adhesive drape after preparation . In the ' no drape ' group ( n = 55 ) the operation site was left uncovered . The two groups were otherwise matched . Swabs for culture were taken from skin adjacent to the wound before closure . The drape group had four positive wound swabs . There was only one positive wound swab for the no-drape group . There was no difference in the post-operative wound infection rates", "Postoperative wound infections in clean surgery were studied to compare the effect of preoperative whole body disinfection with chlorhexidine soap with that of local washing and no washing at all , respectively . The study includes 1530 operations for biliary tract disease , inguinal hernia and breast cancer . The overall infection rate was 3.4 % . Among patient who had a preoperative shower with Chlorhexidine the wound infection rate was significantly reduced", "A r and omized controlled trial has been performed to assess the value of plastic wound drapes in the prevention of surgical wound infection . One hundred and forty‐four patients undergoing abdominal surgery were allocated to one of three groups ; a control group ( A ) in which st and ard cloth towels were applied to the abdominal wound , group B in which an adhesive plastic drape was added and group C in which a plastic ring protector was inserted into the wound", "BACKGROUND Immobilizing skin microbes is a rational approach to reducing contamination of surgical sites by endogenous microorganisms . METHODS This r and omized , controlled , parallel-group , multicenter , open-label clinical trial ( Clinical Trials.gov NCT00467857 ) enrolled 300 adults scheduled for elective coronary artery bypass graft surgery . Patients received iodine-based skin preparations followed by a cyanoacrylate-based skin sealant or skin preparations alone . Microbiological sample s collected from sternal and graft incision sites immediately before any skin preparation , at the wound border after skin incision , and at the incision after fascial closure were evaluated quantitatively . RESULTS In evaluable patients , mean microbial counts in collected sample s increased at the sternal site after fascial closure compared with after skin incision by 0.37 log10 colony-forming units (CFU)/mL in the skin sealant group ( n=120 ) and by 0.57 log10 CFU/mL in the control group ( n=132 ) ( p=0.047 , Wilcoxon rank sum test ) . At the graft site , mean microbial counts increased by 0.09 ( n=119 ) and 0.27 ( n=127 ) log10 CFU/mL , respectively ( p=0.037 ) . There was a 35.3 % relative risk reduction in surgical site infection ( SSI ) occurring in the skin sealant group ( 9 of 146 patients , 6.2 % ) versus the control group ( 14 of 147 patients , 9.5 % ) . In obese patients ( body mass index [ BMI ] > 30.0 to ≤37.0 kg/m2 ) , the relative risk reduction for SSI associated with skin sealant was 83.3 % . CONCLUSIONS Pretreatment with skin sealant protects against contamination of the surgical incision by migration of skin microbes . Further data are needed to confirm the impact of this technology on SSI rates in clinical practice", "A prospect i ve r and omized investigation was undertaken , involving 168 consecutive patients undergoing laparotomy for conditions accompanying bacterially contaminated peritoneal cavities , to evaluate the effectiveness of povidone-iodine irrigation of the peritoneum in preventing the development of intra-abdominal abscesses . In the treatment group irrigated with povidone-iodine solution , 0.1 per cent available iodine , one of 80 patients had an abscess , 1.3 per cent , while , in the saline solution irrigated control group , nine of 88 patients had abscesses , 10.2 per cent , p less than 0.05 . Although the serum iodine levels were elevated 24 hours after intraperitoneal irrigation with povidone-iodine solution , iodine levels returned to near normal by 72 hours . Thyroxine levels showed no major changes . No complications result ing from the use of povidone-iodine were recognized", "Two hundred forty-six patients with acute appendicitis were r and omly assigned to one of two groups . One group of 120 patients received systemic clindamycin preoperatively . Another group of 126 patients received , in addition to systemic clindamycin , a solution of topical ampicillin applied to subcutaneous tissues . No differences were found in the characteristics of the two groups . Combined prophylaxis with clindamycin and ampicillin significantly reduced wound infection to 4 % , compared with clindamycin alone ( p less than 0.02 ) . A decrease in the surgical wound infection rate in the group treated with clindamycin and ampicillin was mainly observed in patients with advanced ( gangrenous and perforated ) appendicitis ( p less than 0.05 ) . A significant decrease in wound infection rates in patients with positive culture results was also found . We conclude that prophylaxis with a combination of systemic clindamycin and topical ampicillin solution , when compared with clindamycin alone , more effectively prevents wound infection after emergency appendectomy , especially in patients with serious wound contamination", "BACKGROUND Surgical site infection is a common complication of surgery . Its morbidities range from delayed healing to systemic sepsis . It has impact on the economy and health care re sources . METHODS This study was a prospect i ve , r and omized , double-blinded , controlled multicenter study aim ed to compare triclosan-coated polyglactin 910 sutures with polyglactin 910 sutures for the reduction of surgical site infections . This article details the results from the Cairo University center . A total of 450 patients who had undergone different surgical procedures were enrolled ; 230 were enrolled in the study group and 220 were enrolled in the control group . RESULTS The study group and the control group were comparable regarding risk factors for surgical site infection . Surgical site infection incidence was 7 % in the study group and 15 % in the control group ( P = .011 ) . The mean extended stay as a result of infection was 3.71 days , with an average cost $ 91 US per day . CONCLUSIONS Use of the triclosan-coated polyglactin 910 antimicrobial suture lead to reduction of surgical site infection and has an impact on saving health care re sources . The triclosan-coated polyglactin 910 antimicrobial suture could save $ 1,517,727 yearly in this single center", "BACKGROUND The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge . Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin . METHODS 2509 patients scheduled to undergo elective total hip arthroplasty were r and omly assigned , stratified according to centre , with a computer-generated r and omisation code , to receive oral rivaroxaban 10 mg once daily for 31 - 39 days ( with placebo injection for 10 - 14 days ; n=1252 ) , or enoxaparin 40 mg once daily subcutaneously for 10 - 14 days ( with placebo tablet for 31 - 39 days ; n=1257 ) . The primary efficacy outcome was the composite of deep-vein thrombosis ( symptomatic or asymptomatic detected by m and atory , bilateral venography ) , non-fatal pulmonary embolism , and all-cause mortality up to day 30 - 42 . Analyses were done in the modified intention-to-treat population , which consisted of all patients who had received at least one dose of study medication , had undergone planned surgery , and had adequate assessment of thromboembolism . This study is registered at Clinical Trials.gov , number NCT00332020 . FINDINGS The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group . The primary outcome occurred in 17 ( 2.0 % ) patients in the rivaroxaban group , compared with 81 ( 9.3 % ) in the enoxaparin group ( absolute risk reduction 7.3 % , 95 % CI 5.2 - 9.4 ; p on-treatment bleeding was much the same in both groups ( 81 [ 6.6 % ] events in 1228 patients in the rivaroxaban safety population vs 68 [ 5.5 % ] of 1229 patients in the enoxaparin safety population ; p=0.25 ) . INTERPRETATION Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism , including symptomatic events , in patients undergoing total hip arthroplasty", "OBJECTIVE Use of single-dose antibiotic prophylaxis is associated with reduced antibiotic resistance , lower costs , and fewer problems with drug toxicity and superinfections . We tested the hypothesis that single doses of cefazolin are as effective as a 24-hour regimen of cefazolin in preventing surgical site infections in adults undergoing cardiac procedures . METHODS This r and om , prospect i ve , clinical study included 838 adult patients undergoing elective coronary artery bypass grafting , valve operations , or both . These patients were r and omly given a single dose of cefazolin ( 2 g ) or a 24-hour treatment ( 2-g initial dose , followed by 1 g every 8 hours ) . Investigators blinded to the drug regimen diagnosed wound infections according to Centers for Disease Control and Prevention criteria . Patient clinical and demographic characteristics were noted , with follow-up for 12 postoperative months . The primary objective was to compare the incidence of surgical infections between groups up to 12 months postoperatively . RESULTS A total of 419 patients received single-dose cefazolin , and another 419 received the 24-hour treatment . Surgical site infection occurred in 35 ( 8.3 % ) patients receiving single doses and 15 ( 3.6 % ) patients administered the 24-hour treatment ( P = .004 ) . We identified no differences between groups for mortality or duration of hospitalization ( preoperative hospitalization , intensive care unit stay , and hospitalization after surgical intervention ) . The microorganisms isolated showed a similar distribution in both groups . The germs isolated were gram-positive cocci in 86 % of the surgical site infections . CONCLUSIONS Single-dose cefazolin used as antibiotic prophylaxis in cardiac surgery is associated with a higher surgical site infection rate than the 24-hour , multiple-dose cefazolin regimen", "Background : Currently a lack of consensus exists on the optimum solution and preparation methods needed to decrease bacteria present during forefoot surgery . We therefore compared the effect of povidine-iodine and chlorhexidine gluconate on lowering bacterial load and to study any additional benefits gained by pre-treatment with the use of a bristled brush . Material s and Methods : Fifty consecutive patients undergoing forefoot surgery were recruited into the study and r and omized to receive one of two surgical skin preparations ( Povidine-iodine 1 % with isopropyl alcohol 23 % or Chlorhexidine gluconate 0.5 % with isopropyl alcohol 70 % ) . In addition to the skin preparation of the foot with the r and omized solution , the subjects other foot was also scrubbed with a sterile surgical bristled brush for three minutes and then painted with the same solution . Swabs were taken from three sites and analyzed via qualitative and quantitative analysis before and after prepping . Results : All four preparation methods significantly decreased ( p number of colony forming units . Using two-way analysis of variance , no significant interaction was observed between preparation method and number of colony-forming units , suggesting that no difference in bacterial inhibition between preparation methods . Conclusion : We suggest that either povidone - iodine with no more that 23 % isopropyl alcohol or chlorhexidine gluconate with 70 % isopropyl alcohol be used for surgical preparation in forefoot surgery . No additional benefit in reduction in bacterial load was gained by scrubbing the foot with bristles prior to painting" ]	411850a4-06ff-11f0-808a-c43d1ab1c353
BACKGROUND CONTEXT In 2008 , the Bone and Joint Decade 2000 to 2010 Task Force on Neck Pain and Its Associated Disorders recommended patient education for the management of neck pain . However , the effectiveness of education interventions has recently been challenged . PURPOSE To up date the findings of the Bone and Joint Decade 2000 to 2010 Task Force on Neck Pain and Its Associated Disorders and evaluate the effectiveness of structured patient education for the management of patients with whiplash-associated disorders ( WAD ) or neck pain and associated disorders ( NAD ) . STUDY DESIGN / SETTING Systematic review of the literature and best- evidence synthesis . PATIENT SAMPLE R and omized controlled trials that compared structured patient education with other conservative interventions . OUTCOME MEASURES Self-rated recovery , functional recovery ( eg , disability , return to activities , work , or school ) , pain intensity , health-related quality of life , psychological outcomes such as depression or fear , or adverse effects . METHODS We systematic ally search ed eight electronic data bases ( MEDLINE , EMBASE , CINAHL , PsycINFO , the Cochrane Central Register of Controlled Trials , DARE , PubMed , and ICL ) from 2000 to 2012 . R and omized controlled trials , cohort studies , and case-control studies meeting our selection criteria were eligible for critical appraisal . R and om pairs of independent review ers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria . Scientifically admissible studies were summarized in evidence tables and synthesized following best- evidence synthesis principles . RESULTS We retrieved 4,477 articles . Of those , nine were eligible for critical appraisal and six were scientifically admissible . Four admissible articles investigated patients with WAD and two targeted patients with NAD . All structured patient education interventions included advice on activation or exercises delivered orally combined with written information or as written information alone . Overall , as a therapeutic intervention , structured patient education was equal or less effective than other conservative treatments including massage , supervised exercise , and physiotherapy . However , structured patient education may provide small benefits when combined with physiotherapy . Either mode of delivery ( ie , oral or written education ) provides similar results in patients with recent WAD . CONCLUSIONS This review adds to the Bone and Joint Decade 2000 to 2010 Task Force on Neck Pain and Its Associated Disorders by defining more specifically the role of structured patient education in the management of WAD and NAD . Results suggest that structured patient education alone can not be expected to yield large benefits in clinical effectiveness compared with other conservative interventions for patients with WAD or NAD . Moreover , structured patient education may be of benefit during the recovery of patients with WAD when used as an adjunct therapy to physiotherapy or emergency room care . These benefits are small and short lived	[ "Abstract Whiplash‐associated disorders are common and incur considerable expense in social and economic terms . There are no known effective treatments for those people whose pain and disability persist beyond 3 months . We conducted a r and omized , assessor‐blinded , controlled trial at two centres in Australia . All participants received 3 advice sessions . In addition the experimental group participated in 12 exercise sessions over 6 weeks . Primary outcomes were pain intensity , pain bothersomeness and function measured at 6 weeks and 12 months . Exercise and advice was more effective than advice alone at 6 weeks for all primary outcomes but not at 12 months . The effect of exercise on the 0–10 pain intensity scale was −1.1 ( 95%CI −1.8 to −0.3 , p = 0.005 ) at 6 weeks and −0.2 ( 0.6 to −1.0 , p = 0.59 ) at 12 months ; on the bothersomeness scale the effect was −1.0 ( −1.9 to −0.2 , p = 0.003 ) at 6 weeks and 0.3 ( −0.6 to 1.3 , p = 0.48 ) at 12 months . The effect on function was 0.9 ( 0.3 to 1.6 , p = 0.006 ) at 6 weeks and 0.6 ( −0.1 to 1.4 , p = 0.10 ) at 12 months . High levels of baseline pain intensity were associated with greater treatment effects at 6 weeks and high levels of baseline disability were associated with greater treatment effects at 12 months . In the short‐term exercise and advice is slightly more effective than advice alone for people with persisting pain and disability following whiplash . Exercise is more effective for subjects with higher baseline pain and disability", "Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items", "Abstract Objectives Firstly , to compare the effectiveness of a brief physiotherapy intervention with “ usual ” physiotherapy for patients with neck pain . Secondly , to evaluate the effect of patients ' preferences on outcome . Design Non-inferiority r and omised controlled trial eliciting preferences independently of r and omisation . Setting Physiotherapy departments in a community setting in Yorkshire and north Lincolnshire . Participants 268 patients ( mean age 48 years ) with subacute and chronic neck pain , who were referred by their general practitioner and r and omly assigned to a brief physiotherapy intervention ( one to three sessions ) using cognitive behaviour principles to encourage self management and return to normal function or usual physiotherapy , at the discretion of the physiotherapist concerned . Main outcome measures The Northwick Park neck pain question naire ( NPQ ) , a specific measure of functional disability result ing from neck pain . Also , the short form 36 ( SF-36 ) question naire , a generic , health related , quality of life measure ; and the Tampa scale for kinesophobia , a measure of fear and avoidance of movement . Results At 12 months , patients allocated to usual physiotherapy had a small but significant improvement in NPQ scores compared with patients in the brief intervention group ( mean difference 1.99 , 95 % confidence interval 0.45 to 3.52 ; P = 0.01 ) . Although the result shows a significant inferiority of the intervention , the confidence interval shows that the effect could be in the non-inferiority range for the brief intervention ( below 1.2 points of NPQ score ) . Patients who preferred the brief intervention and received this treatment had similar outcomes to patients receiving usual physiotherapy . Conclusions Usual physiotherapy may be only marginally better than a brief physiotherapy intervention for neck pain . Patients with a preference for the brief intervention may do at least as well with this approach . Additional training for the physiotherapists in cognitive behaviour techniques might improve this approach further", "Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting", "We previously reported the positive results of a population based campaign design ed to alter beliefs about back pain in Victoria , Australia.1 2 The campaign consisted of television commercials which gave clear advice about back pain — for example , stay active and exercise , do not rest for prolonged periods , and stay at work . After the intervention , doctors ' and the community 's beliefs about back pain became significantly more positive , and the number of workers ' cl aims for compensation and medical payments for back pain had declined . To measure sustained change in beliefs about back pain three years after the campaign ended , we repeated telephone surveys in Victoria and in adjacent New South Wales as a control . We used computer assisted question naires given by telephone interview to a r and om sample of the population of Victoria and New South Wales in December", "Study Design . R and omized control trial conducted between June 2000 and September 2002 . Objective . To determine whether a short psycho-educational video shown in the Emergency Department shortly after the injury would produce follow-up pain reductions and reduced medical utilization . Summary of Background Data . Chronic pain following a whiplash injury is one example of the massive medical/legal problem of chronic muscular pain . Approaches using local pain sources ( trigger points ) have shown promise as treatment models for this type of pain . Methods . 1 ) Setting : Emergency Departments ( ED ) and urgent care ( UC ) facilities . 2 ) Patients : 126 patients entering EDs or UCs . 3 ) Intervention : Patients assigned to 12-minute video or care as usual . 4 ) Main Outcome Measures : Short Form Musculoskelatal Function Assessment ( SMFA ) , phone question naires assessing : narcotics use , ER use , UC use , surgical consultations , etc . Results and Conclusions . Patients viewing the video had dramatically lower pain ratings at a 1-month follow ( 6.09 [ 10.6 ] vs. 21.23 [ 17.4 ] , P video group showed superior outcomes ( & khgr;2 ranged from 5 to 35 , P video patients were using narcotics at 6 month post ED visit compared with 36 % of controls . The brief psycho-educational video had a profound effect on subsequent pain and medical utilization", "Study Design . R and omized parallel-group trial with 1-year follow-up . Objective . To evaluate whether education of patients communicated orally by a specially trained nurse is superior to giving patients a pamphlet after a whiplash injury . Summary of Background Data . Long-lasting pain and physical disability after whiplash injuries are related to both serious personal suffering and huge socio-economic costs . Pure educational interventions after such injuries seem generally as effective as more costly interventions , but it is unknown if the way advice is communicated is of any importance . Methods . Participants with relatively mild complaints after car collisions were recruited from emergency departments and GPs . A total of 182 participants were r and omized to either : ( 1 ) a 1 hour-educational session with a specially trained nurse , or ( 2 ) an educational pamphlet . Outcome parameters were neck pain , headache , disability , and return to work . Recovery was defined as scoring pain 0 or 1 ( 0–10 point scale ) and not being off sick at the time of the follow-ups . Results . After 3 , 6 , and 12 months 60 % , 58 % , and 66 % , respectively of the participants had recovered . Group differences were nonsignificant on all outcome parameters , even though the outcome tended to be better for the group receiving personal advice . Conclusion . Prognosis did not differ between patients who received personal education and those who got a pamphlet . However , a systematic tendency toward better outcome with personal communicated information was observed and the question how patients should be educated to reduce the risk of chronicity after whiplash is worth further investigation , since no treatment have been proven to prevent long-lasting symptoms , and all forms of advice or educational therapy are so cheap that even a modest effect justifies its use", "Objectives To compare naprapathic manual therapy with evidence -based care for back or neck pain regarding pain , disability , and perceived recovery . Naprapathy that is common in the Nordic countries and in some states in the United States is characterized by manual manipulations with a focus on soft and connective tissues , aim ing to decrease pain and disability in the musculoskeletal system . Methods Four hundred and nine patients with pain and disability in the back or neck lasting for at least 2 weeks , recruited at 2 large public companies in Sweden in 2005 , were included in this r and omized controlled trial . The 2 interventions were naprapathy , including spinal manipulation/mobilization , massage , and stretching ( Index Group ) and support and advice to stay active and how to cope with pain , according to the best scientific evidence available , provided by a physician ( Control Group ) . Pain , disability , and perceived recovery were measured by question naires at baseline and after 3 , 7 , and 12 weeks . Results At 7-week and 12-week follow-ups , statistically significant differences between the groups were found in all outcomes favoring the Index Group . At 12-week follow-up , a higher proportion in the naprapathy group had improved regarding pain [ risk difference (RD)=27 % , 95 % confidence interval ( CI ) : 17 - 37 ] , disability ( RD=18 % , 95 % CI : 7 - 28 ) , and perceived recovery ( RD=44 % , 95 % CI : 35 - 53 ) . Separate analysis of neck pain and back pain patients showed similar results . Discussion This trial suggests that combined manual therapy , like naprapathy , might be an alternative to consider for back and neck pain patients", "Abstract Objective : To evaluate the effectiveness of a population based , state-wide public health intervention design ed to alter beliefs about back pain , influence medical management , and reduce disability and costs of compensation . Design : Quasi-experimental , non-r and omised , non-equivalent , before and after telephone surveys of the general population and postal surveys of general practitioners with an adjacent state as control group and descriptive analysis of cl aims data base . Setting : Two states in Australia . Participants : 4730 members of general population before and two and two and a half years after campaign started , in a ratio of 2:1:1 ; 2556 general practitioners before and two years after campaign onset . Main outcome measures : Back beliefs question naire , knowledge and attitude statements about back pain , incidence of workers ' financial compensation cl aims for back problems , rate of days compensated , and medical payments for cl aims related to back pain and other cl aims . Results : In the intervention state beliefs about back pain became more positive between successive surveys ( mean improvement in question naire score 1.9 ( 95 % confidence interval 1.3 to 2.5 ) , P Beliefs about back pain also improved among doctors . There was a clear decline in number of cl aims for back pain , rates of days compensated , and medical payments for cl aims for back pain over the duration of the campaign . Conclusions : A population based strategy of provision of positive messages about back pain improves population and general practitioner beliefs about back pain and seems to influence medical management and reduce disability and workers ' compensation costs related to back pain . What is already known on this topic The number of people with disability from back pain has risen rapidly in the past 50 years Most attempts to limit this disability include modification of occupational risk factors or dealing with the problem once it has developed Patients ' attitudes and beliefs play an important part in the development of such chronic disability What this study adds A population based primary prevention intervention that provided explicit advice about back pain improved beliefs about back pain in the general population and knowledge and attitudes in general practitioners The number of workers ' compensation cl aims for back pain decreased and the rate of days compensated and medical payments for back cl aims were", "Objectives Little is known about the effectiveness of therapeutic massage , one of the most popular complementary medical treatments for neck pain . A r and omized controlled trial was conducted to evaluate whether therapeutic massage is more beneficial than a self-care book for patients with chronic neck pain . Methods Sixty-four such patients were r and omized to receive up to 10 massages over 10 weeks or a self-care book . Follow-up telephone interviews after 4 , 10 , and 26 weeks assessed outcomes including dysfunction and symptoms . Log-binomial regression was used to assess whether there were differences in the percentages of participants with clinical ly meaningful improvements in dysfunction and symptoms ( ie , > 5-point improvement on the Neck Disability Index ; > 30 % improvement from baseline on the symptom bothersomeness scale ) at each time point . Results At 10 weeks , more participants r and omized to massage experienced clinical ly significant improvement on the Neck Disability Index [ 39 % vs. 14 % of book group ; relative risk (RR)=2.7 ; 95 % confidence interval ( CI ) , 0.99 - 7.5 ] and on the symptom bothersomeness scale ( 55 % vs. 25 % of book group ; RR=2.2 ; 95 % CI , 1.04 - 4.2 ) . After 26 weeks , massage group members tended to be more likely to report improved function ( RR=1.8 ; 95 % CI , 0.97 - 3.5 ) , but not symptom bothersomeness ( RR=1.1 ; 95 % CI , 0.6 - 2.0 ) . Mean differences between groups were strongest at 4 weeks and not evident by 26 weeks . No serious adverse experiences were reported . Conclusions This study suggests that massage is safe and may have clinical benefits for treating chronic neck pain at least in the short term . A larger trial is warranted to confirm these results", "Abstract Patients with chronic whiplash associated disorders present with varied sensory , motor and psychological features . In this first instance it was question ed whether a multimodal program of physical therapies was an appropriate management to be broadly prescribed for these patients when it was known that some would have sensory features suggestive of a notable pain syndrome . A r and omised controlled trial was conducted with 71 participants with persistent neck pain following a motor vehicle crash to explore this question . Participants were r and omly allocated to receive either a multimodal physiotherapy program ( MPT ) or a self‐management program ( SMP ) ( advice and exercise ) . In the r and omisation process , participants were stratified according to the presence or not of widespread mechanical or cold hyperalgesia . The intervention period was 10 weeks and outcomes were assessed immediately following treatment . Even with the presence of sensory hypersensitivity in 72.5 % of subjects , both groups reported some relief of neck pain and disability ( Neck Disability Index ) and it was superior in the group receiving multimodal physiotherapy ( p = 0.04 ) . Post‐hoc observations however suggested that relief was marginal in the subgroup with both widespread mechanical and cold hyperalgesia . Further research is required to test the validity of this sub‐group observation and to test the effect of the intervention in the long term", "Background .Neck and low back pain are leading causes of morbidity and health care utilization . However , little is known about the characteristics that differentiate those who seek from those who do not seek health care for their pain . Objectives .The objectives of this study were to : 1 ) describe health care utilization for neck and back pain ; 2 ) determine the characteristics of individuals seeking health care for neck and back pain ; and 3 ) identify the characteristics of patients who consult medical doctors , chiropractors , or both . Design . Population -based cross-sectional mailed survey . Subjects . Subjects were r and omly selected adults from the Saskatchewan Health Insurance and Registration File . Measures .Demographic , socio-economic , general health , comorbidity , health-related- quality -of-life , pain severity and health care utilization data were collected . The main outcome was whether subjects with prevalent neck or low back pain visited a health care provider in the previous month . Results .Twenty-five percent of individuals with neck or low back pain visited a health care provider . Seeking health care was associated with disabling neck or back pain , digestive disorders , worse bodily pain and worse physical-role-functioning . Compared with medical patients , fewer chiropractic patients lived in rural areas or reported arthritis , but they reported better social and physical functioning . More patients consulting both providers reported disabling neck or back pain . Conclusions .Individuals seeking care for neck or back pain have worse health status than those who do not seek care . Patients consulting chiropractors alone report fewer comorbidities and are less limited in their activities than those consulting medical doctors", "Objective : To evaluate the influence of a web-based stress management program on neck – shoulder – back pain and perceived pain-relatedness to stress in a prospect i ve and controlled study . Methods : Study points were baseline , after 6 months intervention and at 12 months follow-up on 226 news media employees in two study groups and one control group . Results : Between groups no significant differences were found at any study point . Within groups , the study group with less intensive program improved in pain-relatedness to stress at follow-up . Between baseline and after intervention , the group with more intensive program showed decreased low back pain , and the control group showed less pain-relatedness to stress . Within group differences varied according to pain localization and were inconsistent . Conclusion : Present web-based stress management program did not influence neck-shoulder-back pain or perceived pain-relatedness to stress in stress-intensive occupations", "BACKGROUND Little is known about the effectiveness of treatments for acute whiplash injury . We aim ed to estimate whether training of staff in emergency departments to provide active management consultations was more effective than usual consultations ( Step 1 ) and to estimate whether a physiotherapy package was more effective than one additional physiotherapy advice session in patients with persisting symptoms ( Step 2 ) . METHODS Step 1 was a pragmatic , cluster r and omised trial of 12 NHS Trust hospitals including 15 emergency departments who treated patients with acute whiplash associated disorder of grade s I-III . The hospitals were r and omised by clusters to either active management or usual care consultations . In Step 2 , we used a nested individually r and omised trial . Patients were r and omly assigned to receive either a package of up to six physiotherapy sessions or a single advice session . R and omisation in Step 2 was stratified by centre . Investigator-masked outcomes were obtained at 4 , 8 , and 12 months . Masking of clinicians and patients was not possible in all steps of the trial . The primary outcome was the Neck Disability Index ( NDI ) . Analysis was intention to treat , and included an economic evaluation . The study is registered IS RCT N33302125 . FINDINGS Recruitment ran from Dec 5 , 2005 to Nov 30 , 2007 . Follow-up was completed on Dec 19 , 2008 . In Step 1 , 12 NHS Trusts were r and omised , and 3851 of 6952 eligible patients agreed to participate ( 1598 patients were assigned to usual care and 2253 patients were assigned to active management ) . 2704 ( 70 % ) of 3851 patients provided data at 12 months . NDI score did not differ between active management and usual care consultations ( difference at 12 months 0·5 , 95 % CI -1·5 to 2·5 ) . In Step 2 , 599 patients were r and omly assigned to receive either advice ( 299 patients ) or a physiotherapy package ( 300 patients ) . 479 ( 80 % ) patients provided data at 12 months . The physiotherapy package at 4 months showed a modest benefit compared to advice ( NDI difference -3·7 , -6·1 to -1·3 ) , but not at 8 or 12 months . Active management consultations and the physiotherapy package were more expensive than usual care and single advice session . No treatment-related serious adverse events or deaths were noted . INTERPRETATION Provision of active management consultation did not show additional benefit . A package of physiotherapy gave a modest acceleration to early recovery of persisting symptoms but was not cost effective from a UK NHS perspective . Usual consultations in emergency departments and a single physiotherapy advice session for persistent symptoms are recommended . FUNDING NIHR Health Technology Assessment programme", "& NA ; Regular physical exercise is a cornerstone in rehabilitation programs , but adherence to comprehensive exercise remains low . This study determined the effectiveness of small daily amounts of progressive resistance training for relieving neck/shoulder pain in healthy adults with frequent symptoms ; 174 women and 24 men working at least 30 h per week and with frequent neck/shoulder pain were r and omly assigned to resistance training with elastic tubing for 2 or 12 minutes per day 5 times per week , or weekly information on general health ( control group ) . Primary outcomes were changes in intensity of neck/shoulder pain ( scale 0 to 10 ) , examiner‐verified tenderness of the neck/shoulder muscles ( total tenderness score of 0 to 32 ) , and isometric muscle strength at 10 weeks . Compared with the control group , neck/shoulder pain and tenderness , respectively , decreased 1.4 points ( 95 % confidence interval −2.0 to −0.7 , p group , muscle strength increased 2.0 Nm ( 95 % confidence interval 0.5 to 3.5 Nm , p = 0.01 ) in the 2‐minute group and 1.7 Nm ( 95 % confidence interval 0.2 to 3.3 Nm , p = 0.02 ) in the 12‐minute group . In conclusion , as little as 2 minutes of daily progressive resistance training for 10 weeks results in clinical ly relevant reductions of pain and tenderness in healthy adults with frequent neck/shoulder symptoms . Trial registration : www.is rct n.org/IS RCT N60264809 . In generally healthy adults with frequent neck/shoulder muscle pain , as little as 2 minutes of daily progressive resistance training reduces pain and tenderness", "Prospect i ve single cohort study . To evaluate the NDI by comparison with the SF36 health Survey Question naire . The NDI is a simple ten-item question naire used to assess patients with neck pain . The SF36 measures functional ability , well being and the overall health of patients . It is used as a gold st and ard in health economics to assess the health utility , gain and economic impact of medical interventions . One hundred and sixty patients with neck pain attending the spinal clinic completed self- assessment question naires . A second question naire was completed in 34 patients after a period of 1–2 weeks . The internal consistency of the NDI and SF36 was calculated using Cronbach ’s alpha . The test – retest reliability was assessed using the Bl and and Altman method . The concurrent validity of the NDI with respect to the SF-36 was assessed using Pearson correlations . Both question naires showed robust internal consistency : Cronbach ’s alpha for the NDI scale was acceptable ( 0.864 , 95 % confidence limits 0.825–0.894 ) though slightly smaller than that of the SF36 . The correlations between each item of the NDI scores and the total NDI score ranged from 0.447 to 0.659 , ( all with P The test – retest reliability of the NDI was high ( intra-class correlation 0.93 , 95 % confidence limits 0.86–0.97 ) and comparable with the best values found for SF36 . The correlations between NDI and SF36 domains ranged from −0.45 to −0.74 ( all with P < 0.001 ) . We have shown that the NDI has good reliability and validity and that it compares well with the SF36 in the spinal surgery out patient setting", "& NA ; Although neck pain is a common source of disability , little is known about its incidence and course . We conducted a population ‐based cohort study of 1100 r and omly selected Saskatchewan adults to determine the annual incidence of neck pain and describe its course . Subjects were initially surveyed by mail in September 1995 and followed‐up 6 and 12 months later . The age and gender st and ardized annual incidence of neck pain is 14.6 % ( 95 % confidence interval : 11.3 , 17.9 ) . Each year , 0.6 % ( 95 % confidence interval : 0.0–1.1 ) of the population develops disabling neck pain . The annual rate of resolution of neck pain is 36.6 % ( 95 % confidence interval : 32.7 , 40.5 ) and another 32.7 % ( 95 % confidence interval : 25.5 , 39.9 ) report improvement . Among subjects with prevalent neck pain at baseline , 37.3 % ( 95 % confidence interval : 33.4 , 41.2 ) report persistent problems and 9.9 % ( 95 % confidence interval : 7.4 , 12.5 ) experience an aggravation during follow‐up . Finally , 22.8 % ( 95 % confidence interval : 16.4 , 29.3 ) of those with prevalent neck pain at baseline report a recurrent episode . Women are more likely than men to develop neck pain ( incidence rate ratio=1.67 , 95 % confidence interval 1.08–2.60 ) ; more likely to suffer from persistent neck problems ( incidence rate ratio=1.19 , 95 % confidence interval 1.03–1.38 ) and less likely to experience resolution ( incidence rate ratio=0.75 , 95 % confidence interval 0.63–0.88 ) . Neck pain is a disabling condition with a course marked by periods of remission and exacerbation . Contrary to prior belief , most individuals with neck pain do not experience complete resolution of their symptoms and disability", "Study Design . A r and omized controlled trial of an educational booklet for patients with first-time neck pain . Objective . To assess the clinical impact of a novel educational book on patients ' functional outcomes and beliefs about neck pain . Summary of Background Data . Previous research has shown that a novel education booklet ( The Back Book ) had a positive impact on patients with low back pain ' beliefs and clinical outcomes . The current study sought to evaluate the efficacy of a similar education booklet ( The Neck Book ) for neck-pain patients . Methods . Workers ' compensation patients were given either the experimental booklet , a traditional booklet or no booklet . The primary outcome measures , collected at 2-weeks , 3-months , and 6-months after baseline , were The Fear Avoidance Beliefs Question naire and The Neck Pain and Disability Scale . Health-related functional measures were also collected at these intervals . Results . Only 34 % ( N = 187 ) of an original cohort of patients ( N = 522 ) had data for all of the follow-up periods . For these 187 patients , repeated- measures analyses of covariance , using the baseline measure as the covariate , revealed no significant differences among the 3 groups on any of the outcome measures at any of the follow-up periods . For example , at 6-months , the experimental booklet , traditional booklet , and no-booklet groups reported The Neck Pain and Disability Scale mean scores ( SDs ) of 31.3 ( 15.5 ) , 35.3 ( 17.0 ) , and 31.8 ( 15.6 ) , respectively . Similarly , there were no significant effects for The Fear Avoidance Beliefs Question naire scores—35.9 ( 21.5 ) , 40.3 ( 22.1 ) , and 38.0 ( 23.4 ) , respectively . Conclusion . This study demonstrates that the educational booklets studied were not associated with improved outcomes in patients with neck pain receiving workers ' compensation . Whether these results would apply to a nonworkers ' compensation population requires further study . The loss of many patients to follow-up also makes any other firm conclusions more difficult to determine", "Study Design . Concealed allocation , multicenter , single-blind , r and omized controlled clinical trial . Objective . To assess the efficacy of an educational video in the tertiary prevention of persistent WAD symptoms following rear-end motor vehicle collisions ( MVCs ) . Summary of Background Data . Whiplash-associated disorders ( WAD ) are an important and costly health problem . There is a lack of high quality evidence surrounding efficacy of treatments for WAD . Existing research supports active interventions and early return to regular activities . Methods . Consecutive patients presenting to four tertiary care emergency departments following rear-end MVCs were eligible . Following informed consent , patients were allocated , using central r and omization , to receive an educational video plus usual care or usual care alone . The video provided reassurance , and advice about posture , return to regular activities , exercises , and pain-relief methods . Data were collected by telephone using st and ardized question naires . The primary outcome was presence of Persistent WAD Symptoms at 24 weeks postinjury , based on the frequency and severity of neck , shoulder , or upper back pain . The absolute difference in proportion of patients with persistent WAD symptoms and rate ratios were calculated . Changes in pain scores were compared using the Mann-Whitney U test . Results . The intervention ( n = 206 ) and control ( n = 199 ) groups were similar at baseline ( mean age 38.4 years ; 64 % female ) . Overall , the proportion of subjects with Persistent WAD Symptoms decreased from 89.1 % at baseline to 33.6 % at 24 weeks after injury . At 24 weeks , the proportion of subjects with persistent WAD symptoms in the intervention group was 7.9 % ( 95 % CI , −2.0 , 17.8 ) lower than the control group . The median improvement in pain score at 24 weeks was 3 for the intervention group and 2 for the control group ( P = 0.016 ) . Conclusion . The presence of persistent WAD symptoms following simple rear-end MVCs was high in this sample . The video group demonstrated a trend toward less severe WAD symptoms . We recommend evaluating other educational interventions that could reduce WAD symptoms", "Objectives This study evaluated predictors of poor outcome in patients with neck pain treated by physical therapy , and sought to compare the findings of empirical data with physical therapy practitioners ' subjective perceptions about predictors of outcome . Methods This study was a secondary analysis of data from a r and omized controlled trial assessing physical therapy treatments for neck pain ( n=346 ) . A baseline question naire provided data on a number of potential risk factors of poor outcome at follow-up . Follow-up was conducted at 6 weeks and 6 months by postal question naire with outcome defined separately by perceived ( global ) change and minimal clinical ly important differences in the Northwick Park Neck Pain Question naire ( MCID-NPQ ) . Therapists ' perceptions of predictors for treatment outcome were captured using a separate question naire , and the ratings compared with ranks derived from the 6-month trial data . Results Baseline characteristics accounted for a much greater proportion of explained variance for global change compared with MCID-NPQ at 6 months . Independent biopsychosocial characteristics included manual social class , catastrophizing , anxiety and depression , low treatment expectations , severity of baseline neck pain/disability , presence of comorbid back pain , and older age . Physical therapist ranks correlated highly with those derived from the trial data . Conclusions Significant predictors of outcome were identified , particularly at 6 months , including psychosocial , functional , and demographic indicators . Our findings suggest that physical therapists are collectively aware of the relative importance of physical and psychosocial factors in predicting clinical outcome . However , a significant amount of variability in outcomes in our prognostic models remained largely unexplained , indicating that we need to explore further underlying factors to inform clinical decision-making", "Neck pain is becoming increasingly more common and multiple interventions have been advocated in its management . The literature supports the use of a variety of exercises including specific low load endurance exercises , scapular muscle retraining and neck and upper limb strengthening . Pilates is one form of exercise that is developing in popularity . This pilot uncontrolled study investigates whether a 6-week matwork based Pilates programme can change outcome measures in a group of chronic neck pain patients . Thirteen subjects were assessed on self-report tests ; neck disability index ( NDI ) , patient specific functional scale ( PSFS ) , numerical rating pain scale ( NRPS ) and one objective measure ; the abdominal drawing in test ( ADIT ) . A statistically significant improvement was obtained in the disability outcomes ( NDI and PSFS ) at both 6 and 12 weeks . The NRPS also demonstrated statistical improvement at 12 weeks but not at 6 . The minimal clinical ly important difference ( MCID ) is the score that reflects a change that is meaningful for the patient and this was achieved at 12-weeks for the NDI ( > 5 points ) , PSFS ( > 3 points ) and NRPS ( > 2 points ) . Only 2 subjects reached normal levels in the ADIT at 12-weeks . The results of this pilot study suggest that Pilates has a role to play in reducing pain and disability in neck pain patients", "Study Design . Quasi-experimental , nonr and omized , nonequivalent , parallel group-controlled study involving before and after telephone surveys of the general population . Objective . To measure the magnitude of any sustained change in population beliefs about back pain 3 years after cessation of a population -based intervention design ed to alter beliefs about back pain . Summary of Background Data . A media campaign , which ran between September 1997 and December 1999 in Victoria , Australia , provided simple evidence -based advice about back pain . Following the campaign , there were significant improvements in both community and physicians ' beliefs about back pain , as well as a decline in number of workers ' compensation back cl aims . Methods . The campaign 's impact on population beliefs about back pain and fear-avoidance beliefs was measured using telephone surveys . Demographically identical population groups in Victoria and the adjacent control state , New South Wales , were surveyed at 4 times : before , during , immediately after , and 3 years after the media campaign in Victoria ( surveys 1−4 , respectively ) . Back beliefs were measured using the Back Beliefs Question naire ( BBQ ) ( possible score 9–45 , for which a higher score indicates a more positive belief about low back trouble ) . Fear-avoidance beliefs were measured using the Fear-Avoidance Beliefs Question naire consisting of 2 subscales for physical activity and work activity ( possible scores 0–24 and 0–36 , respectively ) , for which a lower score indicates fewer fear-avoidance beliefs . Results . A total of 6230 individuals in the general population completed the surveys . Large statistically significant improvements in population beliefs about back pain were still observed in Victoria 3 years after cessation of the campaign ( mean scores on the BBQ were 26.5 , 28.4 , 29.7 , and 28.8 for surveys 1–4 , respectively ) . No changes were observed in New South Wales ( mean scores on the BBQ were 26.3 , 26.2 , 26.3 , and 26.1 for surveys 1–4 , respectively ) . Of those individuals who reported back pain during the previous year , fear-avoidance beliefs aboutphysical activity in Victoria were also significantly better than at baseline ( mean scores on the Fear-Avoidance Beliefs Question naire for physical activity were 14.0 , 12.5 , 11.6 , and 12.3 for surveys 1–4 , respectively ) . Conclusions . Significant sustained improvements in population beliefs about back pain were observed 3 years after cessation of a media campaign of provision of positive messages about back pain . This result provides further evidence that a primary preventive strategy of altering population beliefs about back pain may be a highly effective way for reducing back-related disability", "Study Design . Quasi-experimental , nonr and omized , nonequivalent , parallel group-controlled study involving before and after telephone surveys of the general population and postal surveys of general practitioners was conducted , with an adjacent state used as a control group . Objectives . To evaluate the effectiveness of a population -based intervention design ed to alter beliefs about back pain , influence medical management , and reduce disability and workers ’ compensation – related costs . Summary of Background Data . A multimedia campaign begun during 1997 in Victoria , Australia , positively advised patients with back pain to stay active and exercise , not to rest for prolonged periods , and to remain at work . Methods . The campaign ’s impact on population beliefs about back pain and fear-avoidance beliefs was measured in telephone surveys , and the effect of the campaign on the potential management of low back pain by general practitioners was assessed by eliciting their likely approach to two hypothetical scenarios in mailed surveys . Demographically identical population groups in Victoria and the control state , New South Wales , were surveyed at three times : before , during , and after intervention in Victoria . Results . The studies were completed by 4730 individuals in the general population and 2556 general practitioners . There were large statistically significant improvements in back pain beliefs over time in Victoria ( mean scores on the Back Beliefs Question naire , 26.5 , 28.4 , and 29.7 ) , but not in New South Wales ( 26.3 , 26.2 , and 26.3 , respectively ) . Among those who reported back pain during the previous year , fear-avoidance beliefs about physical activity improved significantly in Victoria ( mean scores on the Fear-Avoidance Beliefs Question naire for physical activity , 14 , 12.5 , and 11.6 ) , but not in New South Wales ( 13.3 , 13.6 , and 12.7 , respectively ) . General practitioners in Victoria reported significant improvements over time in beliefs about back pain management , as compared with their interstate colleagues . There were statistically significant interactions between state and time for 7 of 10 responses on management of acute low back pain , and for 6 of 10 responses on management of subacute low back pain . Conclusion . A population -based strategy of providing positive messages about back pain improves the beliefs of the general population and general practitioners about back pain and appears to influence medical management", "OBJECTIVES To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury ; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs ; and to gain participants ' perspective on experiencing whiplash injury , NHS treatment , and recovery within the context of the Managing Injuries of the Neck Trial ( MINT ) . DESIGN Two linked , pragmatic , r and omised controlled trials . In Step 1 , emergency departments ( EDs ) were cluster r and omised to usual care advice ( UCA ) or The Whiplash Book advice (WBA)/active management advice . In Step 2 , participants were individually r and omised to either a single session of advice from a physiotherapist or a physiotherapy package of up to six sessions . An economic evaluation and qualitative study were run in parallel with the trial . SETTING Twelve NHS trusts in Engl and comprising 15 EDs . PARTICIPANTS People who attended EDs with an acute whiplash injury of whiplash-associated disorder grade s I-III were eligible for Step 1 . People who had attended EDs with whiplash injuries and had persistent symptoms 3 weeks after ED attendance were eligible for Step 2 . INTERVENTIONS In Step 1 , the control intervention was UCA and the experimental intervention was a psycho-educational intervention ( WBA/active management advice ) . In Step 2 the control treatment was reinforcement of the advice provided in Step 1 and the experimental intervention was a package of up to six physiotherapy treatments . MAIN OUTCOME The primary outcome was the Neck Disability Index ( NDI ) , which measures severity and frequency of pain and symptoms , and a range of activities including self-care , driving , reading , sleeping and recreation . Secondary outcomes included the mental and physical health-related quality -of-life ( HRQoL ) subscales of the Short Form question naire-12 items ( SF-12 ) and the number of work days lost . RESULTS A total of 3851 patients were recruited to Step 1 of the trial . 1598 patients attending EDs were r and omised to UCA , and 2253 were r and omised to WBA/active management . Outcome data were obtained at 12 months for 70 % and 80 % of participants at Step 1 and Step 2 , respectively . The majority of people recovered from the injury . Eighteen per cent of the Step 1 cohort had late whiplash syndrome . There was no statistically or clinical ly significant difference observed in any of the outcomes for participants attending EDs r and omised to UCA or active management advice [ difference in NDI 0.5 , 95 % confidence interval ( CI ) -1.8 to 2.8 ] . In Step 2 the physiotherapy package result ed in improvements in neck disability at 4 months compared with a single advice session , but these effects were small at the population level ( difference in NDI -3.2 , 95 % CI -5.8 to -0.7 ) . The physiotherapy package was accompanied by a significant reduction in the number of work days lost at 4-month follow-up ( difference -40.2 , 95 % CI -44.3 to -35.8 ) . CONCLUSIONS MINT suggests that enhanced psycho-educational interventions in EDs are no more effective than UCA in reducing the burden of acute whiplash injuries . A physiotherapy package provided to people who have persisting symptoms within the first 6 weeks of injury produced additional short-term benefits in neck disability compared with a single physiotherapy advice session . However , from a health-care perspective , the physiotherapy package was not cost-effective at current levels of willingness to pay . Both experimental treatments were associated with increased cost with no discernible gain in health-related quality of life . However , an important benefit of the physiotherapy package was a reduction in work days lost ; consequently , the intervention may prove cost-effective at the societal level . TRIAL REGISTRATION Current Controlled Trials IS RCT N33302125 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 16 , No. 49 . See the HTA programme website for further project information", "The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline . Thirdly , guideline users are often not clear about the implication s of the grading system . They misinterpret the grade of recommendation as relating to its importance , rather than to the strength of the supporting evidence , and may therefore fail to give due weight to low grade recommendations . # # # # Summary points A revised system of determining levels of evidence and grade s", "There is a serious need to provide effective early interventions that prevent the development of persistent pain and disability . Identifying patients at risk for this development is an important step . Our aim was to explore whether distinct subgroups of individuals with similar response patterns on a screening question naire exist . Moreover , the objective was to then relate these groups to future outcomes , for example , sick leave as an impetus for developing tailored interventions that might better prevent chronic problems . A total of 363 patients seeking primary care for acute or subacute spinal pain completed the Örebro Musculoskeletal Pain Screening Question naire and were then followed to determine outcome . Cluster analysis was used to identify subgroups . Validity was tested using 3 methods including the split-half technique . The subgroups were compared prospect ively on outcome measures obtained 1 year later . Using pain intensity , fear-avoidance beliefs , function , and mood , we found 4 distinct profiles : Fear-Avoidant , Distressed Fear-Avoidant , Low Risk , and Low Risk-Depressed Mood . These 4 subgroups were also robust in all 3 of the validity procedures . The 4 subgroups were clearly related to outcome . Although the low risk profiles had virtually no one developing long-term sick leave , the Fear-Avoidant profile had 35 % and the Distressed Fear-Avoidant profile 62 % developing long-term sick leave . Our results suggest that fear-avoidance and distress are important factors in the development of pain-related disability and may serve as a key for early identification . Providing interventions specific to the factors isolated in the profiles should enhance the prevention of persistent pain and disability", "PURPOSE The objective of this study is to investigate the effect of three different workplace interventions on long-term compliance , muscle strength gains , and neck/shoulder pain in office workers . METHODS A 1-yr r and omized controlled intervention trial was done with three groups : specific resistance training ( SRT , n = 180 ) , all-round physical exercise ( APE , n = 187 ) , and reference intervention ( REF , n = 182 ) with general health counseling . Physical tests were performed and question naires answered at pre- , mid- , and postintervention . The main outcome measures were compliance , changes in maximal muscle strength , and changes in intensity of neck/shoulder pain ( scale 0 - 9 ) in those with and without pain at baseline . RESULTS Regular participation was achieved by 54 % , 31 % , and 16 % of those of the participants who answered the question naire in SRT ( 78 % ) , APE ( 81 % ) , and REF ( 80 % ) , respectively , during the first half of the intervention period , and decreased to 35 % , 28 % and 9 % , respectively , during the second half . Shoulder elevation strength increased 9 - 11 % in SRT and APE ( P Participants with neck pain at baseline decreased the intensity of neck pain through SRT , from 5.0 + /- 0.2 to 3.4 + /- 0.2 ( P pain over the 1-yr period in REF compared with SRT and APE ( P shoulder elevation strength , were more effective than REF to decrease neck pain among those with symptoms at baseline , and prevent development of shoulder pain in those without symptoms at baseline", "Objectives To estimate the sensitivity to change and internal consistency of the Northwick Park Neck Pain Question naire ( NPQ ) and derive its minimal clinical ly important difference ( MCID ) . Methods Data on 311 participants in a r and omized controlled trial of physical therapy for neck pain were analyzed , between baseline and 6-month follow-up . Cronbach α was used to estimate internal consistency . Three methods of evaluating the NPQ 's sensitivity to change were used ; Cohen 's effect size , st and ardized response mean , and Guyatt 's responsiveness statistic . The smallest change on the NPQ that can be construed as clinical ly important ( the MCID ) was obtained by ( 1 ) comparing values derived from different methods that account for the measurement error of the question naire with improvements in other neck pain-specific measures , and then ( 2 ) examining the impact of the addition of an independent measure ( “ anchor ” ) relating to participants ' subjective rating of improvement . Results Cronbach α was 0.79 for the whole scale . Using all participants , Cohen 's d was 0.78 , st and ardized response mean was 0.71 , and Guyatt 's responsiveness statistic was 0.93 . Using only participants who stated they had improved , the estimates were 1.35 , 1.27 , 1.45 , respectively . The MCID for the NPQ was determined as a 25 % reduction in score from baseline together with a patient 's global rating of their neck pain of at least “ better . ” Conclusions These results show high internal consistency and sensitivity to change for the NPQ , and provide an MCID that allows participants with varying levels of severity to demonstrate improvement", "There is growing evidence for the idea that in back pain patients , pain-related fear ( fear of pain/physical activity/(re)injury ) may be more disabling than pain itself . A number of question naires have been developed to quantify pain-related fears , including the Fear-Avoidance Beliefs Question naire ( FABQ ) , the Tampa Scale for Kinesiophobia ( TSK ) , and the Pain Anxiety Symptoms Scale ( PASS ) . A total of 104 patients , presenting to a rehabilitation center or a comprehensive pain clinic with chronic low back pain were studied in three independent studies aim ed at ( 1 ) replicating that pain-related fear is more disabling than pain itself ( 2 ) investigating the association between pain-related fear and poor behavioral performance and ( 3 ) investigating whether pain-related fear measures are better predictors of disability and behavioral performance than measures of general negative affect or general negative pain beliefs ( e.g. pain catastrophizing ) . All three studies showed similar results . Highest correlations were found among the pain-related fear measures and measures of self-reported disability and behavioral performance . Even when controlling for sociodemographics , multiple regression analyses revealed that the subscales of the FABQ and the TSK were superior in predicting self-reported disability and poor behavioral performance . The PASS appeared more strongly associated with pain catastrophizing and negative affect , and was less predictive of pain disability and behavioral performance . Implication s for chronic back pain assessment , prevention and treatment are discussed" ]	41185126-06ff-11f0-808a-c43d1ab1c353
Neck pain and whiplash injuries are a common presentation to the ED , and a frequent cause of disability globally . This rapid review investigated best practice for the assessment and management of musculoskeletal neck pain in the ED . PubMed , CINAHL , EMBASE , TRIP and the grey literature , including relevant organisational websites , were search ed in 2017 . Primary studies , systematic review s and guidelines were considered for inclusion . English- language articles published in the past 12 years addressing acute neck pain assessment , management or prognosis in the ED were included . Data extraction was conducted , followed by quality appraisal to rate levels of evidence where possible . The search revealed 2080 articles , of which 51 were included ( n = 22 primary articles , n = 13 systematic review s and n = 16 guidelines ) . Consistent evidence was found to support the use of ' red flags ' to screen for serious pathologies , judicious use of imaging through clinical decision rule application and promotion of functional exercise coupled with advice and reassurance . Clinicians may also consider applying risk-stratification methods , such as using a clinical prediction rule , to guide patient discharge and referral plans ; however , the evidence is still emerging in this population . This rapid review provides clinicians managing neck pain in the ED a summary of the best available evidence to enhance quality of care and optimise patient outcomes	[ "Purpose To construct and vali date a prediction instrument for early identification of patients with a high risk of delayed recovery after whiplash injuries ( PPS-WAD ) in an insurance company setting . Methods Prospect i ve cohort study . On the basis of a historic cohort ( n = 130 ) of patients with a whiplash injury identified in an emergency room ( ER , model-building set ) , we used logistic regression to construct an instrument consisting of two demographic variables ( i.e. questions of educational level and work status ) and the patient-rated physical and mental status during the acute phase to predict self-reported nonrecovery after 6 months . We evaluated the instrument ’s ability to predict nonrecovery in a new cohort ( n = 204 ) of patients originating from an insurance company setting ( IC , validation set ) . Results The prediction instrument had low reproducibility when the setting was changed from the ER cohort to the IC cohort . The overall percentage of correct predictions of nonrecovery in the ER cohort was 78 % compared with 62 % in the IC cohort . The sensitivity and specificity in relation to nonrecovery were both 78 % in the ER cohort . The sensitivity and specificity in the insurance company setting was lower , 67 and 50 % . Conclusion Clinical decision rules need validation before they are used in a new setting . An instrument consisting of four questions with an excellent possibility of identifying patients with a high risk of nonrecovery after a whiplash injury in the emergency room was not as useful in an insurance company setting . The importance and type of the risk factors for not recovering probably differ between the setting s , as well as the individuals", "PURPOSE We systematic ally review ed r and omized and quasi-r and omized clinical trials in the literature to assess the efficacy of neck stabilization and postural exercises on pain , neck range of motion , and time off work in adults with acute whiplash-associated disorders . METHODS Electronic data bases , reference lists of relevant Cochrane review s , reference lists of studies selected for inclusion , and tables of contents of relevant journals were systematic ally search ed for r and omized and quasi-r and omized controlled trials . Two independent review ers selected studies for inclusion , assessed method ological quality , and extracted data . Because of the heterogeneity of the interventions , a qualitative synthesis was performed using \" levels of evidence \" as recommended by van Tulder et al. RESULTS Eight studies representing five clinical trials were selected for inclusion . Two trials were grade d as high quality , two as moderate quality , and one as low quality . Many of these studies had mixed results , demonstrating significant differences on some outcome measures but not on others . CONCLUSIONS There is moderate evidence to support the use of postural exercises for decreasing pain and time off work in the treatment of patients with acute whiplash-associated disorders . However , no evidence exists to support the use of postural exercises for increasing neck range of motion . There is conflicting evidence in support of neck stabilization exercises in the treatment of patients with acute whiplash-associated disorders", "The aim of the prospect i ve cohort study was to investigate the outcome of acute whiplash injury first treated either by junior doctors ( JD ) [ ≤3 postgraduate years ( PGY ) ] or more experienced doctors ( MED ) ( > 3 PGY ) . At baseline , crash-related data and health parameters including the SF36 were evaluated in whiplash patients ( WP ) , who fulfilled criteria for whiplash-associated disorders grade I – II and presented up to 48 h after motor vehicle accident to our Emergency Department . 81 WP were recruited and treated by either one of 14 JD ( 35 WP ) or one of 22 MED ( 46 WP ) . The follow-up examination included the course of pain intensity [ numeric rating scale ( NRS ) 0–10 ] by the use of a 28 days-pain-diary and the incidence of symptoms ( st and ardized-telephone-interview at 1 , 3 , and 6 months post trauma ) in terms of neck pain NRS > 2 , analgesic medication , work-off , and utilization of further medical services as well as SF36 evaluated at the end of the study . Although the entry population seemed similar , all outcome parameters were comparable between the JD- and MED-group ( p > 0.05 ) . Therefore , we conclude that seniority of the first-treating physician does not influence the outcome of acute whiplash injury", "OBJECTIVE To investigate whether whiplash injury may be a trigger for the onset of fibromyalgia ( FM ) . METHODS One hundred fifty-three patients presenting to the emergency room with the diagnosis of whiplash injury were examined . The control group included 53 patients hospitalized with fractures of the limbs , spine , and ribs due to road accident . The study and control groups were interviewed shortly after presenting and then followed prospect ively . Patients complaining of musculoskeletal symptoms during followup were examined and a count of 18 tender points was conducted . FM was diagnosed if the patient fulfilled currently accepted 1990 American College of Rheumatology criteria . RESULTS The mean followup period for the study and control groups was 14.5 months ( range 12 - 18 ) and 9 months ( range 6 - 14 ) , respectively . There were no differences between the groups with regard to age , sex , marital , education , or employment status . During the followup period only one patient in the study group and no patients in the control group developed signs and symptoms of FM . Three patients in the study group ( 2 % ) and 15 patients in the control group ( 16 % ) filed insurance cl aims ; none was associated with FM . CONCLUSION Whiplash injury and road accident trauma were not associated with an increased rate of FM after more than 14.5 months of followup", "Neck pain is the cardinal symptom following whiplash injuries . The trauma mechanism could theoretically lead to both soft tissue and bone injury that could be visualised by means of MRI . From previous quite small trials it seems that MRI does not demonstrate significant tissue damage . Large prospect ively followed cohorts are needed to identify possible clinical ly relevant MRI findings . The objective of this trial was to evaluate ( 1 ) the predictive value of cervical MRI after whiplash injuries and ( 2 ) the value of repeating MRI examinations after 3 months including sequences with flexion and extension of the cervical spine . Participants were included after rear-end or frontal car collisions . Patients with fractures or dislocations diagnosed by st and ard procedures at the emergency unit were not included . MRI scans of the cervical spine were performed at baseline and repeated after 3 months . Clinical follow-ups were performed after 3 and 12 months . Outcome parameters were neck pain , headache , neck disability and working ability . A total of 178 participants had a cervical MRI scan on average 13 days after the injury . Traumatic findings were observed in seven participants . Signs of disc degeneration were common and most frequent at the C5–6 and C6–7 levels . Findings were not associated with outcome after 3 or 12 months . The population had no considerable neck trouble prior to the whiplash injury and the non-traumatic findings represent findings to be expected in the background population . Trauma-related MRI findings are rare in a whiplash population screened for serious injuries in the emergency unit and not related to a specific symptomatology . Also , pre-existing degeneration is not associated with prognosis", "Summary Background Back pain remains a challenge for primary care internationally . One model that has not been tested is stratification of the management according to the patient 's prognosis ( low , medium , or high risk ) . We compared the clinical effectiveness and cost-effectiveness of stratified primary care ( intervention ) with non-stratified current best practice ( control ) . Methods 1573 adults ( aged ≥18 years ) with back pain ( with or without radiculopathy ) consultations at ten general practice s in Engl and responded to invitations to attend an assessment clinic . Eligible participants were r and omly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group . Primary outcome was the effect of treatment on the Rol and Morris Disability Question naire ( RMDQ ) score at 12 months . In the economic evaluation , we focused on estimating incremental quality -adjusted life years ( QALYs ) and health-care costs related to back pain . Analysis was by intention to treat . This study is registered , number IS RCT N37113406 . Findings 851 patients were assigned to the intervention ( n=568 ) and control groups ( n=283 ) . Overall , adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months ( 4·7 [ SD 5·9 ] vs 3·0 [ 5·9 ] , between-group difference 1·81 [ 95 % CI 1·06–2·57 ] ) and at 12 months ( 4·3 [ 6·4 ] vs 3·3 [ 6·2 ] , 1·06 [ 0·25–1·86 ] ) , equating to effect sizes of 0·32 ( 0·19–0·45 ) and 0·19 ( 0·04–0·33 ) , respectively . At 12 months , stratified care was associated with a mean increase in generic health benefit ( 0·039 additional QALYs ) and cost savings ( £ 240·01 vs £ 274·40 ) compared with the control group . Interpretation The results show that a stratified approach , by use of prognostic screening with matched pathways , will have important implication s for the future management of back pain in primary care . Funding Arthritis Research UK", "Objective To evaluate the effectiveness of an active strategy to implement the vali date d Canadian C-Spine Rule into multiple emergency departments . Design Matched pair cluster r and omised trial . Setting University and community emergency departments in Canada . Participants 11 824 alert and stable adults presenting with blunt trauma to the head or neck at one of 12 hospitals . Interventions Six hospitals were r and omly allocated to the intervention and six to the control . At the intervention sites , active strategies were used to implement the Canadian C-Spine Rule , including education , policy , and real time reminders on radiology requisitions . No specific intervention was introduced to alter the behaviour of doctors requesting cervical spine imaging at the control sites . Main outcome measure Diagnostic imaging rate of the cervical spine during two 12 month before and after periods . Results Patients were balanced between control and intervention sites . From the before to the after periods , the intervention group showed a relative reduction in cervical spine imaging of 12.8 % ( 95 % confidence interval 9 % to 16 % ; 61.7 % v 53.3 % ; P=0.01 ) and the control group a relative increase of 12.5 % ( 7 % to 18 % ; 52.8 % v 58.9 % ; P=0.03 ) . These changes were significant when both groups were compared ( P fractures were missed and no adverse outcomes occurred . Conclusions Implementation of the Canadian C-Spine Rule led to a significant decrease in imaging without injuries being missed or patient morbidity . Final imaging rates were much lower at intervention sites than at most US hospitals . Widespread implementation of this rule could lead to reduced healthcare costs and more efficient patient flow in busy emergency departments worldwide . Trial registration Clinical trials NCT00290875", "Summary This r and omised trial showed that multiprofessional stratified management had no effect beyond usual care in reducing transition rates to chronicity in patients with acute whiplash . ABSTRACT Acute whiplash is a heterogeneous disorder that becomes persistent in 40 % to 60 % of cases . Estimates of recovery have not changed in recent decades . This r and omized , single‐blind , controlled trial tested whether multidisciplinary individualized treatments for patients with acute whiplash ( could reduce the incidence of chronicity at 6 mo by 50 % compared to usual care . Participants ( n = 101 ) were recruited from accident and emergency centres and the community . It was hypothesized that better recovery rates were achievable if the heterogeneity was recognised and patients received individualised interventions . Patients r and omized to pragmatic intervention ( n = 49 ) could receive pharmaceutical management ( ranging from simple medications to opioid analgesia ) , multimodal physiotherapy and psychology for post‐traumatic stress according to their presentations . The treatment period was 10 wks with follow‐up at 11 weeks and 6 and 12‐months . The primary outcome was neck pain and disability ( Neck Disability Index ( NDI ) ) . Analysis revealed no significant differences in frequency of recovery ( NDI ≤8 % ) between pragmatic and usual care groups at 6 months ( OR 95 % , CI = 0.55 , 0.23–1.29 ) , P = 0.163 ) or 12 mo ( OR 95 % , CI = 0.65 , 0.28–1.47 , P = 0.297 ) . There was no improvement in current nonrecovery rates at 6 mo ( 63.6 % , pragmatic care ; 48.8 % , usual care ) , indicating no advantage of the early multiprofessional intervention . Baseline levels of pain and disability had a significant bearing on recovery both at 6 and 12 mo in both groups , suggesting that future research focus on finding early effective pain management , particularly for the subgroup of patients with initial high levels of pain and disability , towards improving recovery rates", "Study Design . A prospect i ve observational cohort study of alert , neurologically intact trauma patients presenting to the emergency department with midline cervical tenderness . Screening cervical magnetic resonance imaging ( MRI ) had been conducted after negative computed tomography ( CT ) when tenderness was persistent . Objective . To determine the association of acute findings and demographic characteristics with any long-term neck disability , and with time to return to work in such patients . Summary of Background Data . The relationship between acute findings and outcomes in these patients is unknown , and we hypothesized that outcomes at 12 months would correlate with acute clinical signs and symptoms , MRI findings , and mechanisms of injury . Methods . Patients at a Level 1 trauma center with persistent midline cervical tenderness in the absence of evidence of intoxication , painful distracting injury , persistently abnormal neurology , or acute CT findings , who underwent early cervical MRI under the institutional protocol , were review ed in the outpatient spine clinic after discharge . In addition , the factors associated with neck disability and time to return to work were examined at follow-up at 12 months after presentation . Results . There were 162 of 178 patients available for follow-up at 12 months ( 91 % ) . Of these , 46 % had MRI-identified cervical spine injury at their initial examination , and 22 % had required clinical management , including 2.5 % with operative stabilization . Neck disability was present in 43 % of patients and was associated with depressive symptoms , workers ' compensation , and low annual income . Delay in return to work was associated with the presence of minor limb/other fractures and depressive symptoms , whereas patients on high annual incomes were found to return to work more quickly . Conclusion . Surprisingly in these acute trauma patients , MRI-detected injury , clinical factors , and injury mechanism were not found to be associated with long-term patient outcomes . As a result , a trial of a more targeted , individual return to work plan , including strategies aim ed at improving physical and psychological function , may now be justified to optimize long-term recovery , reduce health re source costs , and maximize economic productivity through early return to work", "This is a 1-year prospect i ve study to investigate the prognostic value of coping strategies such as catastrophising for persistent pain after a whiplash injury . A consecutive series of 96 patients who were seen in the emergency room in the acute phase after the injury were followed prospect ively for 1 year . Age , gender and whether or not pain in the neck preceded the accident was recorded . Cases involving fractures or dislocations of the cervical spine , head trauma or pre-existing neurological disorders were not included . The mean interval between the accident and the initial examination was 3+/-2(S.D. ) days . Coping was measured using the Coping Strategies Question naire ( CSQ ) . The outcome parameter was self-reported neck pain at 1 year after the motor vehicle accident . At 1 year , 34 % of the patients had neck pain . Women developed chronic neck pain more often than men ( 71 % versus 29 % ) ; they also had significantly higher coping activity , such as diverting attention , praying or hoping ( p catastrophising and increasing behavioural activities ( p pain in the neck or shoulder more often before the accident and this was the only statistically significant predictor of chronic symptoms when analysed by logistic regression ( odds ratio 4.5 ) . To conclude , we found no evidence that the different coping patterns during the early phase after a whiplash injury influenced the prognosis", "Musculoskeletal injuries are a common presentation to the ED , with significant costs involved in the management of these injuries , variances in care within the ED and associated morbidity . A series of rapid review papers were completed to guide best practice for the assessment and management of common musculoskeletal injuries presenting to the ED . This paper presents the methodology used across the rapid review s. PubMed , CINAHL , EMBASE , TRIP and the grey literature , including relevant organisational websites , were search ed in 2015 . The search was repeated consistently for each topic area ( injuries of the foot and ankle , knee , h and and wrist , elbow , shoulder , lumbar spine and cervical spine ) . English- language primary studies , systematic review s and guidelines that were published in the last 10 years and addressed acute musculoskeletal injury management were considered for inclusion . Data extraction of each included article was conducted , followed by a quality appraisal . The extracted data from each article was synthesis ed to group similar evidence together . For each rapid review , the evidence has been organised in a way that a clinician can direct their attention to a specific component of the clinical cycle of care in the ED , such as the assessment , diagnostic tests , management and follow-up considerations from ED . The series of rapid review s are design ed to foster evidence -based practice within the ED , targeting the injuries most commonly presenting . The review s provide clinicians in EDs with rapid access to the best current evidence , which has been synthesis ed and organised to assist decision-making", "Objective : To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms . Design : Prospect i ve cohort study . Patients recruited from hospital emergency departments were sent a question naire to gather information on various exposures . They were followed up at 1 , 3 , and 12 months to identify those with persistent symptoms . Main outcome measure : Persistent neck pain ( pain at 1 , 3 , and 12 months after collision ) . Results : The baseline survey included 765 patients . Subsequently , 480 completed a question naire at each follow up time point , of whom 128 ( 27 % ) reported neck pain on each occasion . Few collision specific factors predicted persistent neck pain . In contrast , a high level of general psychological distress , pre-collision history of widespread body pain , type of vehicle , whiplash associated symptoms , and initial neck disability best predicted the persistence of symptoms . Furthermore , these factors , in combination , accounted for more than a fivefold increase in the risk of persistent neck pain . Conclusion : The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself . With these factors , and those relating to initial injury severity , it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms . Thus , it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals", "OBJECTIVE The purpose of this study was to prospect ively assess the sensitivity and efficacy of clinical examination for screening of cervical spine ( c-spine ) injury in awake and alert blunt trauma patients with concomitant “ distracting injuries . ” METHODS During the 24-month period from December 2009 to December 2011 , all blunt trauma patients older than 13 years were prospect ively evaluated with a st and ard cervical spine examination protocol by the trauma surgery team at a Level 1 trauma center . Awake and alert patients with a Glasgow Coma Score ( GCS ) ≥14 underwent clinical examination of the cervical spine . Clinical examination was performed regardless of “ distracting injuries . ” Patients without complaints of pain or tenderness on physical exam had their cervical collar removed , and the c-spine was considered clinical ly cleared of injury . All awake and alert patients with “ distracting injuries , ” including those clinical ly cleared and those with complaints of c-spine pain or tenderness underwent computerized tomographic ( CT ) scanning of the entire c-spine . “ Distracting injuries ” were categorized into three anatomic regions : head injuries , torso injuries and long bone fractures . Patients with minor distracting injuries were not considered to have a “ distracting injury . ” RESULTS During the 24-month study period , 761 blunt trauma patients with GCS ≥14 and at least one “ distracting injury ” had been entered into the study protocol . Two-hundred ninety-six ( 39 % ) of the patients with “ distracting injuries ” had a positive c-spine clinical examination , 85 ( 29 % ) of whom were diagnosed with c-spine injury . Four hundred sixty-four ( 61 % ) of the patients with “ distracting injuries ” were initially clinical ly cleared , with one patient ( 0.2 % ) diagnosed with a c-spine injury . This yielded an overall sensitivity of 99 % ( 85/86 ) and negative predictive value greater than 99 % ( 463/464 ) for cervical spine clinical examination in awake and alert blunt trauma patients with “ distracting injuries . ” CONCLUSIONS In the awake and alert blunt trauma patient with “ distracting injuries , ” clinical examination is a sensitive screening method for cervical spine injury . Radiological assessment is unnecessary for safe clearance of the asymptomatic cervical spine in awake and alert blunt trauma patients with “ distracting injuries . ” These findings suggest the concept of “ distracting injury ” in the context of cervical spine clinical examination is invalid . Exp and ing the utility of cervical spine clinical examination to patients with “ distracting injuries ” allows for significant reduction of both healthcare cost and radiation exposure . LEVEL OF EVIDENCE Diagnostic study , level", "Objectives : The Canadian C-Spine Rule for imaging of the cervical spine was developed for use by physicians . We believe that nurses in the emergency department could use this rule to clinical ly clear the cervical spine . We prospect ively evaluated the accuracy , reliability and acceptability of the Canadian C-Spine Rule when used by nurses . Methods : We conducted this three-year prospect i ve cohort study in six Canadian emergency departments . The study involved adult trauma patients who were alert and whose condition was stable . We provided two hours of training to 191 triage nurses . The nurses then assessed patients using the Canadian C-Spine Rule , including determination of neck tenderness and range of motion , reapplied immobilization and completed a data form . Results : Of the 3633 study patients , 42 ( 1.2 % ) had clinical ly important injuries of the cervical spine . The kappa value for interobserver assessment s of 498 patients with the Canadian C-Spine Rule was 0.78 . We calculated sensitivity of 100.0 % ( 95 % confidence interval [ CI ] 91.0%–100.0 % ) and specificity of 43.4 % ( 95 % CI 42.0%–45.0 % ) for the Canadian C-Spine Rule as interpreted by the investigators . The nurses classified patients with a sensitivity of 90.2 % ( 95 % CI 76.0%–95.0 % ) and a specificity of 43.9 % ( 95 % CI 42.0%–46.0 % ) . Early in the study , nurses failed to identify four cases of injury , despite the presence of clear high-risk factors . None of these patients suffered sequelae , and after retraining there were no further missed cases . We estimated that for 40.7 % of patients , the cervical spine could be cleared clinical ly by nurses . Nurses reported discomfort in applying the Canadian C-Spine Rule in only 4.8 % of cases . Conclusion : Use of the Canadian C-Spine Rule by nurses was accurate , reliable and clinical ly acceptable . Widespread implementation by nurses throughout Canada and elsewhere would diminish patient discomfort and improve patient flow in overcrowded emergency departments", "Abstract Purpose To evaluate the effectiveness of non-steroidal anti-inflammatory drugs ( NSAIDs ) for the management of neck pain and associated disorders ( NAD ) , whiplash-associated disorders , and non-specific low back pain ( LBP ) with or without radiculopathy . Methods We systematic ally search ed six data bases from 2000 to 2014 . R and om pairs of independent review ers critically appraised eligible systematic review s using the Scottish Intercollegiate Guidelines Network criteria . We included systematic review s with a low risk of bias in our best evidence synthesis . Results We screened 706 citations and 14 systematic review s were eligible for critical appraisal . Eight systematic review s had a low risk of bias . For recent-onset NAD , evidence suggests that intramuscular NSAIDs lead to similar outcomes as combined manipulation and soft tissue therapy . For NAD ( duration not specified ) , oral NSAIDs may be more effective than placebo . For recent-onset LBP , evidence suggests that : ( 1 ) oral NSAIDs lead to similar outcomes to placebo or a muscle relaxant ; and ( 2 ) oral NSAIDs with bed rest lead to similar outcomes as placebo with bed rest . For persistent LBP , evidence suggests that : ( 1 ) oral NSAIDs are more effective than placebo ; and ( 2 ) oral NSAIDs may be more effective than acetaminophen . For recent-onset LBP with radiculopathy , there is inconsistent evidence on the effectiveness of oral NSAIDs versus placebo . Finally , different oral NSAIDs lead to similar outcomes for neck and LBP with or without radiculopathy . Conclusions For NAD , oral NSAIDs may be more effective than placebo . Oral NSAIDs are more effective than placebo for persistent LBP , but not for recent-onset LBP . Different oral NSAIDs lead to similar outcomes for neck pain and LBP", "STUDY DESIGN Retrospective secondary analysis of data . OBJECTIVES To investigate the external validity of the whiplash clinical prediction rule ( CPR ) . BACKGROUND We recently derived a whiplash CPR to consoli date previously established prognostic factors for poor recovery from a whiplash injury and predicted 2 recovery pathways . Prognostic factors for full recovery were being less than 35 years of age and having an initial Neck Disability Index ( NDI ) score of 32 % or less . Prognostic factors for ongoing moderate/severe pain and disability were being 35 years of age or older , having an initial NDI score of 40 % or more , and the presence of hyperarousal symptoms . Validation is required to confirm the reproducibility and accuracy of this CPR . Clinician feedback on the usefulness of the CPR is also important to gauge acceptability . METHODS A secondary analysis of data from 101 individuals with acute whiplash-associated disorder who had previously participated in either a r and omized controlled clinical trial or prospect i ve cohort study was performed using accuracy statistics . Full recovery was defined as NDI score at 6 months of 10 % or less , and ongoing moderate/severe pain and disability were defined as an NDI score at 6 months of 30 % or greater . In addition , a small sample of physical therapists completed an anonymous survey on the clinical acceptability and usability of the tool . Results The positive predictive value of ongoing moderate/severe pain and disability was 90.9 % in the validation cohort , and the positive predictive value of full recovery was 80.0 % . Surveyed physical therapists reported that the whiplash CPR was simple , underst and able , would be easy to use , and was an acceptable prognostic tool . CONCLUSION External validation of the whiplash CPR confirmed the reproducibility and accuracy of this dual-pathway tool for individuals with acute whiplash-associated disorder . Further research is needed to assess prospect i ve validation , the impact of inclusion on practice , and to examine the efficacy of linking treatment strategies with predicted prognosis . LEVEL OF EVIDENCE Prognosis , level 1b", "OBJECTIVES Acute back and neck strains are very common . In addition to administering analgesics , these strains are often treated with either heat or cold packs . The objective of this study was to compare the analgesic efficacy of heat and cold in relieving pain from back and neck strains . The authors hypothesized that pain relief would not differ between hot and cold packs . METHODS This was a r and omized , controlled trial conducted at a university-based emergency department ( ED ) with an annual census of 90,000 visits . ED patients > 18 years old with acute back or neck strains were eligible for inclusion . All patients received 400 mg of ibuprofen orally and then were r and omized to 30 minutes of heating pad or cold pack applied to the strained area . Outcomes of interest were pain severity before and after pack application on a vali date d 100-mm visual analog scale ( VAS ) from 0 ( no pain ) to 100 ( worst pain ) , percentage of patients requiring rescue analgesia , subjective report of pain relief on a verbal rating scale ( VRS ) , and future desire for similar packs . Outcomes were compared with t-tests and chi-square tests . A sample of 60 patients had 80 % power to detect a 15-mm difference in pain scores . RESULTS Sixty patients were r and omized to heat ( n = 31 ) or cold ( n = 29 ) therapy . Mean ( + /-st and ard deviation [ SD ] ) age was 37.8 ( + /-14.7 ) years , 51.6 % were female , and 66.7 % were white . Groups were similar in baseline patient and pain characteristics . There were no differences between the heat and cold groups in the severity of pain before ( 75 mm [ 95 % CI = 66 to 83 ] vs. 72 mm [ 95 % CI = 65 to 78 ] ; p = 0.56 ) or after ( 66 mm [ 95 % CI = 57 to 75 ] vs. 64 mm [ 95 % CI = 56 to 73 ] ; p = 0.75 ) therapy . Pain was rated better or much better in 16/31 ( 51.6 % ) and 18/29 ( 62.1 % ) patients in the heat and cold groups , respectively ( p = 0.27 ) . There were no between-group differences in the desire for and administration of additional analgesia . Twenty-five of 31 ( 80.6 % ) patients in the heat group and 22 of 29 ( 75.9 % ) patients in the cold group would use the same therapy if injured in the future ( p = 0.65 ) . CONCLUSIONS The addition of a 30-minute topical application of a heating pad or cold pack to ibuprofen therapy for the treatment of acute neck or back strain results in a mild yet similar improvement in the pain severity . However , it is possible that pain relief is mainly the result of ibuprofen therapy . Choice of heat or cold therapy should be based on patient and practitioner preferences and availability", "OBJECTIVE To evaluate whether current Dutch primary care clinicians offer tailored treatment to patients with low back pain ( LBP ) or neck pain ( NP ) according to their risk stratification , based on the Keele STarT ( Subgroup Targeted Treatment ) Back-Screening Tool ( SBT ) . DESIGN Prospect i ve cohort study with 3-month follow-up . SETTING Primary care . PARTICIPANTS General practitioners ( GPs ) and physiotherapists included patients ( N=284 ) with nonspecific LBP , NP , or both . INTERVENTIONS Patients completed a baseline question naire , including the Dutch SBT , for either LBP or NP . A follow-up measurement was conducted after 3 months to determine recovery ( using Global Perceived Effect Scale ) , pain ( using Numeric Pain Rating Scale ) , and function ( using Rol and Disability Question naire or Neck Disability Index ) . A question naire was sent to the GPs and physiotherapists to evaluate the provided treatment . MAIN OUTCOME MEASURES Prevalence of patients ' risk profile and clinicians ' applied care , and the percentage of patients with persisting disability at follow-up . A distinction was made between patients receiving the recommended treatment and those receiving the nonrecommended treatment . RESULTS In total , 12 GPs and 33 physiotherapists included patients . After 3 months , we analyzed 184 patients with LBP and 100 patients with NP . In the LBP group , 52.2 % of the patients were at low risk for persisting disability , 38.0 % were at medium risk , and 9.8 % were at high risk . Overall , 24.5 % of the patients with LBP received a low-risk treatment approach , 73.5 % a medium-risk , and 2.0 % a high-risk treatment approach . The specific agreement between the risk profile and the received treatment for patients with LBP was poor for the low-risk and high-risk patients ( 21.1 % and 10.0 % , respectively ) , and fair for medium-risk patients ( 51.4 % ) . In the NP group , 58.0 % of the patients were at low risk for persisting disability , 37.0 % were at medium risk , and 5.0 % were at high risk . Only 6.1 % of the patients with NP received the low-risk treatment approach . The medium-risk treatment approach was offered the most ( 90.8 % ) , and the high-risk approach was applied in only 3.1 % of the patients . The specific agreement between the risk profile and received treatment for patients with NP was poor for low-risk and medium-risk patients ( 6.3 % and 48.0 % , respectively ) ; agreement for high-risk patients could not be calculated . CONCLUSIONS Current Dutch primary care for patients with nonspecific LBP , NP , or both does not correspond to the recommended stratified-care approach based on the SBT , as most patients receive medium-risk treatment . Most low-risk patients are overtreated , and most high-risk patients are undertreated . Although the stratified-care approach has not yet been vali date d in Dutch primary care , these results indicate there may be substantial room for improvement", "Study Design . Single-center prospect i ve longitudinal study . Objective . To study the ( 1 ) temporal development of muscle fatty infiltrates ( MFI ) in the cervical multifidi after whiplash , ( 2 ) differences in multifidi MFI between those who recover or report milder pain – related disability and those who report moderate/severe symptoms at 3 months , and ( 3 ) predictive value of multifidi MFI outcomes . Summary of Background Data . The temporal development of MFI on conventional magnetic resonance image has been shown to be associated with specific aspects of pain and psychological factors . The replication of such findings has yet to be explored longitudinally . Methods . Thirty-six subjects with whiplash injury were enrolled at less than 1 week postinjury and classified at 3 months using percentage scores on the Neck Disability Index as recovered/mild ( 0%–28 % ) or severe ( ≥30 % ) . A fat/water magnetic resonance imaging measure , patient self-report of pain-related disability , and post-traumatic stress disorder were collected at less than 1 week , 2 weeks , and 3 months postinjury . The effects of time and group ( per Neck Disability Index ) and the interaction of time by group on MFI were determined . Receiver operating characteristic curve analysis was used to determine a cut-point for MFI at 2 weeks to predict outcome at 3 months . Results . There was no difference in MFI across groups at enrolment . MFI values were significantly higher in the severe group than those in the recovered/mild group at 2 weeks and 3 months . The receiver operating characteristic curve analysis indicated that MFI levels of 20.5 % or above result ed in a sensitivity of 87.5 % and a specificity of 92.9 % for predicting outcome at 3 months . Conclusion . Consistent with previous evidence , muscle degeneration occurs soon after injury but only in those patients with poor functional recovery . This study provides further evidence that ( 1 ) multifidi MFI occur in t and em with known predictive risk factors ( older age , pain-related disability , and post-traumatic stress disorder ) and ( 2 ) routine imaging protocol s may need to be reconsidered in the vast majority of patients after whiplash . Level of Evidence :", "Summary A clinical prediction rule comprising relevant biopsychosocial factors was derived to predict both chronic moderate/severe disability and full recovery following whiplash injury . Abstract Recovery following a whiplash injury is varied : approximately 50 % of individuals fully recover , 25 % develop persistent moderate/severe pain and disability , and 25 % experience milder levels of disability . Identification of individuals likely to develop moderate/severe disability or to fully recover may help direct therapeutic re sources and optimise treatment . A clinical prediction rule ( CPR ) is a research ‐generated tool used to predict outcomes such as likelihood of developing moderate/severe disability or experiencing full recovery from whiplash injury . The purpose of this study was to assess the plausibility of developing a CPR . Participants from 2 prospect i ve , longitudinal studies that examined prognostic factors for poor functional recovery following whiplash injury were used to derive this tool . Eight factors , previously identified as predictor variables of poor recovery , were included in the analyses : initial neck disability index ( NDI ) , initial neck pain ( visual analogue scale ) , cold pain threshold , range of neck movement , age , gender , presence of headache , and posttraumatic stress symptoms ( Posttraumatic Diagnostic Scale [ PDS ] ) . An increased probability of developing chronic moderate/severe disability was predicted in the presence of older age and initially higher levels of NDI and hyperarousal symptoms ( PDS ) ( positive predictive value [ PPV ] = 71 % ) . The probability of full recovery was increased in younger individuals with initially lower levels of neck disability ( PPV = 71 % ) . This study provides initial evidence for a CPR to predict both chronic moderate/severe disability and full recovery following a whiplash injury . Further research is needed to vali date the tool , determine the acceptability of the proposed CPR by practitioners , and assess the impact of inclusion in practice" ]	4118519e-06ff-11f0-808a-c43d1ab1c353
Background Activity monitoring devices are currently being used to facilitate and monitor physical activity . No prior review has examined adherence to the use of activity monitoring devices amongst adults with cardiovascular disease . Methods Literature from June 2012 to October 2017 was evaluated to examine the extent of adherence to any activity monitoring device used to collect objective physical activity data . R and omized control trials comparing usual care against the use of an activity monitoring device , in a community intervention for adults from any cardiovascular diagnostic group , were included . A systematic search of data bases and clinical trials registers was conducted using Joanna Briggs Institute methodology . Results Of 10 eligible studies , two studies reported pedometer use and eight accelerometer use . Six studies addressed the primary outcome . Mean adherence was 59.1 % ( range 39.6 % to 85.7 % ) at last follow-up . Studies lacked equal representation by gender ( 28.6 % female ) and age ( range 42 to 82 years ) . Conclusion This review indicates that current research on activity monitoring devices may be overstated due to the variability in adherence . Results showed that physical activity tracking in women and in young adults have been understudied	[ "Background Angina affects more than 50 million people worldwide . Secondary prevention interventions such as cardiac rehabilitation are not widely available for this population . An Internet-based version could offer a feasible alternative . Objective Our aim was to examine the effectiveness of a Web-based cardiac rehabilitation program for those with angina . Methods We conducted a r and omized controlled trial , recruiting those diagnosed with angina from general practitioners ( GPs ) in primary care to an intervention or control group . Intervention group participants were offered a 6-week Web-based rehabilitation program ( “ ActivateYourHeart ” ) . The program was introduced during a face-to-face appointment and then delivered via the Internet ( no further face-to-face contact ) . The program contained information about the secondary prevention of coronary heart disease ( CHD ) and set each user goals around physical activity , diet , managing emotions , and smoking . Performance against goals was review ed throughout the program and goals were then reset/modified . Participants completed an online exercise diary and communicated with rehabilitation specialists through an email link/synchronized chat room . Participants in the control group continued with GP treatment as usual , which consisted of being placed on a CHD register and attending an annual review . Outcomes were measured at 6-week and 6-month follow-ups during face-to-face assessment s. The primary outcome measure was change in daily steps at 6 weeks , measured using an accelerometer . Secondary outcome measures were energy expenditure ( EE ) , duration of sedentary activity ( DSA ) , duration of moderate activity ( DMA ) , weight , diastolic/systolic blood pressure , and body fat percentage . Self-assessed question naire outcomes included fat/fiber intake , anxiety/depression , self-efficacy , and quality of life ( QOL ) . Results A total of 94 participants were recruited and r and omized to the intervention ( n=48 ) or the usual care ( n=46 ) group ; 84 and 73 participants completed the 6-week and 6-month follow-ups , respectively . The mean number of log-ins to the program was 18.68 ( SD 13.13 , range 1 - 51 ) , an average of 3 log-ins per week per participant . Change in daily steps walked at the 6-week follow-up was + 497 ( SD 2171 ) in the intervention group and –861 ( SD 2534 ) in the control group ( 95 % CI 263 - 2451 , P=.02 ) . Significant intervention effects were observed at the 6-week follow-up in EE ( + 43.94 kcal , 95 % CI 43.93 - 309.98 , P=.01 ) , DSA ( –7.79 minutes , 95 % CI –55.01 to –7.01 , P=.01 ) , DMA ( + 6.31 minutes , 95 % CI 6.01 - 51.20 , P=.01 ) , weight ( –0.56 kg , 95 % CI –1.78 to –0.15 , P=.02 ) , self-efficacy ( 95 % CI 0.30 - 4.79 , P=.03 ) , emotional QOL score ( 95 % CI 0.01 - 0.54 , P=.04 ) , and angina frequency ( 95 % CI 8.57 - 35.05 , P=.002 ) . Significant benefits in angina frequency ( 95 % CI 1.89 - 29.41 , P=.02 ) and social QOL score ( 95 % CI 0.05 - 0.54 , P=.02 ) were also observed at the 6-month follow-up . Conclusions An Internet-based secondary prevention intervention could be offered to those with angina . A larger pragmatic trial is required to provide definitive evidence of effectiveness and cost-effectiveness . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 90110503 ; http://www.controlled-trials.com/IS RCT N90110503/IS RCT N90110503 ( Archived by WebCite at http://www.webcitation.org/6RYVOQFKM )", "Background The construct of total wellness includes a holistic approach to the body , mind and spirit components of life . While the health benefits of reducing sedentary behavior and increasing physical activity are well documented , little is known about the influence on total wellness of an internet-based physical activity monitor design ed to help people to achieve higher physical activity levels . Purpose The purpose of this four-week , personal activity monitor-based intervention program was to reduce sedentary behavior and increase physical activity levels in daily living for sedentary adults and to determine if these changes would also be associated with improvement in total wellness . Methods Twenty-two men and 11 women ( 27 years ± 4.0 ) were r and omly assigned to either an intervention ( n = 18 ) or control group ( n = 15 ) . The intervention group interacted with an online personal activity monitor ( Gruve Solution ™ ) design ed to reduce sedentary time and increase physical activity during activities of daily living . The control group did not interact with the monitor , as they were asked to follow their normal daily physical activities and sedentary behavior routines . The Wellness Evaluation of Lifestyle ( WEL ) inventory was used to assess total wellness . Sedentary time , light , walking , moderate and vigorous intensity physical activities were assessed for both intervention and control groups at baseline and at week-4 by the 7-day Sedentary and Light Intensity Physical Activity Log ( 7-day SLIPA Log ) and the International Physical Activity Question naire ( IPAQ ) . Results Significant increases in pre-post total wellness scores ( from 64 % ± 5.7 to 75 % ± 8.5 ) ( t ( 17 ) = -6.5 , p their sedentary time ( 21 % , 2.3 hours/day ) and increased their light ( 36.7 % , 2.5 hours/day ) , walking ( 65 % , 1057 MET-min/week ) , moderate ( 67 % , 455 MET-min/week ) and vigorous intensity ( 60 % , 442 MET-min/week ) physical activity ( all p for total wellness were observed between the groups at baseline and no pre-post significant differences were observed for any outcome variable in the control group . Conclusion Total wellness is improved when sedentary , but sufficiently physically active adults , reduce sedentary time and increase physical activity levels ( i.e. light , waking , moderate and vigorous )", "Background — Exercise training is an effective treatment for important atrial fibrillation ( AF ) comorbidities . However , a high level of endurance exercise is associated with an increased AF prevalence . We assessed the effects of aerobic interval training ( AIT ) on time in AF , AF symptoms , cardiovascular health , and quality of life in AF patients . Methods and Results — Fifty-one patients with nonpermanent AF were r and omized to AIT ( n=26 ) consisting of four 4-minute intervals at 85 % to 95 % of peak heart rate 3 times a week for 12 weeks or to a control group ( n=25 ) continuing their regular exercise habits . An implanted loop recorder measured time in AF continuously from 4 weeks before to 4 weeks after the intervention period . Cardiac function , peak oxygen uptake ( O2peak ) , lipid status , quality of life , and AF symptoms were evaluated before and after the 12-week intervention period . Mean time in AF increased from 10.4 % to 14.6 % in the control group and was reduced from 8.1 % to 4.8 % in the exercise group ( P=0.001 between groups ) . AF symptom frequency ( P=0.006 ) and AF symptom severity ( P=0.009 ) were reduced after AIT . AIT improved O2peak , left atrial and ventricular ejection fraction , quality -of-life measures of general health and vitality , and lipid values compared with the control group . There was a trend toward fewer cardioversions and hospital admissions after AIT . Conclusions — AIT for 12 weeks reduces the time in AF in patients with nonpermanent AF . This is followed by a significant improvement in AF symptoms , O2peak , left atrial and ventricular function , lipid levels , and QoL. Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01325675", "Objective Cardiac rehabilitation ( CR ) is pivotal in preventing recurring events of myocardial infa rct ion ( MI ) . This study aims to investigate the effect of a smartphone-based home service delivery ( Care Assessment Platform ) of CR ( CAP-CR ) on CR use and health outcomes compared with a traditional , centre-based programme ( TCR ) in post-MI patients . Methods In this unblinded r and omised controlled trial , post-MI patients were r and omised to TCR ( n=60 ; 55.7±10.4 years ) and CAP-CR ( n=60 ; 55.5±9.6 years ) for a 6-week CR and 6-month self-maintenance period . CAP-CR , delivered in participants ’ homes , included health and exercise monitoring , motivational and educational material delivery , and weekly mentoring consultations . CAP-CR uptake , adherence and completion rates were compared with TCR using intention-to-treat analyses . Changes in clinical outcomes ( modifiable lifestyle factors , biomedical risk factors and health-related quality of life ) across baseline , 6 weeks and 6 months were compared within , and between , groups using linear mixed model regression . Results CAP-CR had significantly higher uptake ( 80 % vs 62 % ) , adherence ( 94 % vs 68 % ) and completion ( 80 % vs 47 % ) rates than TCR ( p improvements in 6-minute walk test from baseline to 6 weeks ( TCR : 537±86–584±99 m ; CAP-CR : 510±77–570±80 m ) , which was maintained at 6 months . CAP-CR showed slight weight reduction ( 89±20–88±21 kg ) and also demonstrated significant improvements in emotional state ( K10 : median ( IQR ) 14.6 ( 13.4–16.0 ) to 12.6 ( 11.5–13.8 ) ) , and quality of life ( EQ5D-Index : median ( IQR ) 0.84 ( 0.8–0.9 ) to 0.92 ( 0.9–1.0 ) ) at 6 weeks . Conclusions This smartphone-based home care CR programme improved post-MI CR uptake , adherence and completion . The home-based CR programme was as effective in improving physiological and psychological health outcomes as traditional CR . CAP-CR is a viable option towards optimising use of CR services . Trial registration number ANZCTR12609000251224", "Background Although many wearable devices for monitoring and tracking physical activity are available to consumers , relatively few research studies have been conducted to determine their efficacy in promoting health . Methods In this article , data on the use of consumer wearable devices in promoting healthy behaviors are summarized based upon bibliographic search es in PubMed and Psychology and Behavioral Sciences Collection with relevant search terms through September 2016 . Results A total of 274 articles were identified in the bibliographic search es . By screening abstract s or full-text articles , six pre/post test trials and seven r and omized controlled trials were identified . In initial trials , consumer wearable devices have been shown to increase physical activity and help users lose weight . However , the number of studies completed to date is small and limited by small sample sizes , short study duration s , and uncertain generalizability of the findings . Conclusions Future studies should utilize r and omized controlled trial research design s , larger sample sizes , and longer study periods to better establish the efficacy of wearable devices in promoting physical activity . Additional research is needed to determine the feasibility and effectiveness of wearable devices in promoting physical activity and weight loss in community setting s including communities affected by health disparities . Studies focusing on children and adolescents are also needed", "Background Heart failure ( HF ) patients discharged from rural hospitals have higher 30-day readmission rates . Self-management ( SM ) reduces readmissions , but adherence to SM guidelines is low in the rural HF population . We tested a home-based intervention to enhance patient activation and lead to improved SM adherence . Methods In this two-group , repeated measures r and omized control trial , the main outcomes were patient reported and clinical outcomes associated with SM adherence , and all-cause readmission at 30 , 90 and 180 days . Results The study included 100 HF patients discharged from a rural critical access hospital . The intervention group received a 12-week SM training and coaching program delivered by telephone and tailored on subjects ’ activation levels . At α = .10 , the PATCH intervention showed significantly greater improvement compared to usual care in patient-reported SM adherence : weighing themselves , following a low-sodium diet , taking prescribed medication , and exercising daily ( all p in physical activity assessed by actigraphy or in clinical biomarkers . Contrary to expectation , the 30-day readmission rate was significantly higher ( p = .088 ) in the intervention group ( 19.6 % ) than in the control group ( 6.1 % ) , with no differences at 90 or 180 days . Conclusion It is feasible to conduct a r and omized controlled trial in HF patients discharged from rural critical access hospitals . Significantly higher patient-reported SM adherence was not accompanied by lower clinical biomarkers or readmission rates . Further research is needed to underst and mechanisms that influence outcomes and healthcare utilization in this population .Trial registration Clinical Trial Registration Information : Clinical Trials.gov ; NCT01964053", "Background Lack of physical activity ( PA ) is a known risk factor for many health conditions . The workplace is a setting often used to promote activity and health . We investigated the effectiveness of an intervention on PA and productivity-related outcomes in an occupational setting . Methods We conducted a r and omized controlled trial of 12 months duration with two 1:1 allocated parallel groups of insurance company employees . Eligibility criteria included permanent employment and absence of any condition that risked the participant ’s health during PA . Subjects in the intervention group monitored their daily PA with an accelerometer , set goals , had access to an online service to help them track their activity levels , and received counseling via telephone or web messages for 12 months . The control group received the results of a fitness test and an information leaflet on PA at the beginning of the study . The intervention ’s aim was to increase PA , improve work productivity , and decrease sickness absence . Primary outcomes were PA ( measured as MET minutes per week ) , work productivity ( quantity and quality of work ; QQ index ) , and sickness absence ( SA ) days at 12 months . Participants were assigned to groups using block r and omization with a computer-generated scheme . The study was not blinded . Results There were 544 r and omized participants , of which 521 were included in the analysis ( 64 % female , mean age 43 years ) . At 12 months , there was no significant difference in physical activity levels between the intervention group ( n = 264 ) and the control group ( n = 257 ) . The adjusted mean difference was −206 MET min/week [ 95 % Bayesian credible interval −540 to 128 ; negative values favor control group ] . There was also no significant difference in the QQ index ( −0.5 [ −4.4 to 3.3 ] ) or SA days ( 0.0 [ −1.2 to 0.9 ] ) . Of secondary outcomes , body weight ( 0.5 kg [ 0.0 to 1.0 ] ) and percentage of body fat ( 0.6 % [ 0.2 % to 1.1 % ] ) were slightly higher in the intervention group . An exploratory subgroup analysis revealed no subgroups in which the intervention affected physical activity . No adverse events were reported . Conclusions The intervention was not found effective , and this study does not provide support for the effectiveness of the workplace PA intervention used here . Trial registration Clinical Trials.gov identifier :", "Background Cardiac telerehabilitation has been introduced as an adjunct or alternative to conventional center-based cardiac rehabilitation to increase its long-term effectiveness . However , before large-scale implementation and reimbursement in current health care systems is possible , well- design ed studies on the effectiveness of this new additional treatment strategy are needed . Objective The aim of this trial was to assess the medium-term effectiveness of an Internet-based , comprehensive , and patient-tailored telerehabilitation program with short message service ( SMS ) texting support for cardiac patients . Methods This multicenter r and omized controlled trial consisted of 140 cardiac rehabilitation patients r and omized ( 1:1 ) to a 24-week telerehabilitation program in combination with conventional cardiac rehabilitation ( intervention group ; n=70 ) or to conventional cardiac rehabilitation alone ( control group ; n=70 ) . In the telerehabilitation program , initiated 6 weeks after the start of ambulatory rehabilitation , patients were stimulated to increase physical activity levels . Based on registered activity data , they received semiautomatic telecoaching via email and SMS text message encouraging them to gradually achieve predefined exercise training goals . Patient-specific dietary and /or smoking cessation advice was also provided as part of the telecoaching . The primary endpoint was peak aerobic capacity ( VO2 peak ) . Secondary endpoints included accelerometer-recorded daily step counts , self-assessed physical activities by International Physical Activity Question naire ( IPAQ ) , and health-related quality of life ( HRQL ) assessed by the HeartQol question naire at baseline and at 6 and 24 weeks . Results Mean VO2 peak increased significantly in intervention group patients ( n=69 ) from baseline ( mean 22.46 , SD 0.78 mL/[minkg ] ) to 24 weeks ( mean 24.46 , SD 1.00 mL/[minkg ] , P of aerobic capacity confirmed a significant difference between the intervention group and control group in favor of the intervention group ( P self-reported physical activity improved more in the intervention group compared to the control group ( P=.01 ) as did the global HRQL score ( P=.01 ) . Conclusions This study showed that an additional 6-month patient-specific , comprehensive telerehabilitation program can lead to a bigger improvement in both physical fitness ( VO2 peak ) and associated HRQL compared to center-based cardiac rehabilitation alone . These results are supportive in view of possible future implementation in st and ard cardiac care", "BACKGROUND Physical activity contributes to improve health and quality of life . However , the prevalence of sedentary lifestyle is elevated after an acute coronary syndrome . METHODS A r and omized controlled trial was performed to evaluate the impact of a pedometer-based program associated with a socio-cognitive intervention on physical activity behaviour , cardiovascular risk factors , and quality of life during the year after an acute coronary syndrome event . During hospitalization , we r and omized 32 patients to an experimental group and 33 patients to a usual care group . The experimental intervention included 6 consultations with a clinical nurse specialist during 12 months . RESULTS Groups characteristics were comparable . At baseline , the percentage of participants considered in the active range category was similar between groups ( 31 % vs 41 % ; P = 0.915 ) . However , the proportion of participants who were still active was greater in the experimental group than in the usual care group at 6 , 9 , and 12 months follow-up ( 75 % vs 41 % ; 68 % vs 36 % , and 83 % vs 55 % , respectively ; P overall quality of life and in health and the functioning scores were different between groups ( interaction effects [ groups by time ] P = 0.048 and P = 0.036 , respectively ) . CONCLUSIONS The use of a pedometer concomitantly with a socio-cognitive intervention improves adherence to physical activity and quality of life during the year after an acute coronary syndrome event . This finding is relevant because physical activity and quality of life are a great concern in preventive cardiology . These results support applying this innovative approach in cardiac rehabilitation programs", "OBJECTIVE To assess the efficacy of a strategy , based on telephone support oriented by accelerometer measurements , on the adherence to physical activity ( PA ) recommendations in cardiac patients not achieving PA recommendations . DESIGN Prospect i ve and r and omized study . SETTING A cardiac rehabilitation program ( CRP ) at a clinic . PARTICIPANTS Stable , noncompliant cardiac ( coronary artery disease , heart failure , post-cardiovascular surgery ) patients ( weekly moderate-intensity PA control group ( n=10 ) . INTERVENTIONS The intervention group wore an accelerometer for 8 weeks . Every 15 days , feedback and support were provided by telephone . The control group wore the accelerometer during the 8th week of the intervention only . MAIN OUTCOME MEASURES Active energy expenditure ( EE ) ( in kilocalories ) and the time spent doing light , moderate , or intense PA ( minutes per week ) . RESULTS In the intervention group , the time spent at moderate-intensity PA increased from 95.6±80.7 to 137.2±87.5 min/wk between the 1st and 8th week ( P=.002 ) , with 36.8 % of the sample achieving the target amount of moderate-intensity PA . During the 8th week , the EE averaged 543.7±144.1 kcal and 266.7±107.4 kcal in the intervention group and control group , respectively ( P=.004 ) . CONCLUSIONS Telephone support based on accelerometer recordings appeared to be an effective strategy to improve adherence to PA in noncompliant patients . This intervention could be implemented after a CRP as an inexpensive , modern , and easy-to-use strategy", "The purpose of this study was to compare a technology-based system , an in-person behavioral weight loss intervention , and a combination of both over a 6-month period in overweight adults . Fifty-one subjects ( age : 44.2 ± 8.7 years , BMI : 33.7 ± 3.6 kg/m(2 ) ) participated in a 6-month behavioral weight loss program and were r and omized to one of three groups : st and ard behavioral weight loss ( SBWL ) , SBWL plus technology-based system ( SBWL+TECH ) , or technology-based system only ( TECH ) . All groups reduced caloric intake and progressively increased moderate intensity physical activity . SBWL and SBWL+TECH attended weekly meetings . SBWL+TECH also received a TECH that included an energy monitoring armb and and website to monitor energy intake and expenditure . TECH used the technology system and received monthly telephone calls . Body weight and physical activity were assessed at 0 and 6 months . Retention at 6 months was significantly different ( P = 0.005 ) between groups ( SBWL : 53 % , SBWL+TECH : 100 % , and TECH : 77 % ) . Intent-to-treat ( ITT ) analysis revealed significant weight losses at 6 months in SBWL+TECH ( -8.8 ± 5.0 kg , -8.7 ± 4.7 % ) , SBWL ( -3.7 ± 5.7 kg , -4.1 ± 6.3 % ) , and TECH ( -5.8 ± 6.6 kg , -6.3 ± 7.1 % ) ( P increased significantly in SBWL ( 473.9 ± 800.7 kcal/week ) , SBWL+TECH ( 713.9 ± 1,278.8 kcal/week ) , and TECH ( 1,066.2 ± 1,371 kcal/week ) ( P not greater weight losses and changes in physical activity than the st and ard in-person behavioral program at 6 months . The use of this technology may provide an effective short-term clinical alternative to st and ard in-person behavioral weight loss interventions , with the longer term effects warranting investigation", "OBJECTIVE To assess the effects of an exercise-based cardiac rehabilitation programme on daily physical activity levels of patients following myocardial infa rct ion . DESIGN Sub analysis of two r and omised , prospect i ve controlled trials . SETTING Outpatient clinic of a secondary hospital . PARTICIPANTS Fifty consecutive patients r and omised to the exercise group { n=25 ; 23 males ; mean age 54 [ st and ard deviation ( SD ) 9 ] years } or the control group [ n=25 ; 20 males ; mean age 58 ( SD 9 ) years ] . INTERVENTIONS The exercise group participated in an 8-week aerobic exercise programme plus usual medical care and follow-up . The control group received usual medical care and follow-up . MAIN OUTCOME MEASURES The primary outcome measure was change in time spent undertaking moderate-to-vigorous physical activity per day , assessed by accelerometer over 7 consecutive days . Secondary outcome measures were cardiorespiratory fitness , body mass , and resting blood pressure and heart rate . RESULTS Moderate-to-vigorous physical activity levels increased significantly in the exercise group [ 43.2 ( SD 36.3 ) to 53.5 ( SD 31.9 ) minutes/day , P=0.030 ] , and remained unchanged in the control group [ 40.8 ( SD 26.2 ) to 36.8 ( SD 26.5 ) minutes/day , P=0.241 ] from baseline to the end of the programme . Cardiorespiratory fitness increased significantly in the exercise group ( mean difference 2.8 ; 95 % of the difference 1.3 to 4.4ml/kg/minute , P=0.001 ) after the 8-week programme . CONCLUSIONS In patients under optimal medication following myocardial infa rct ion , participation in an 8-week exercise-based cardiac rehabilitation programme was found to improve physical activity levels consistent with health-related benefits . Future studies are needed to determine whether the increase in physical activity is maintained in the long term", "Abstract Purpose : Important goals of cardiac rehabilitation maintenance programs ( CMP ) are to increase leisure time physical activity ( LTPA ) and improve health-related quality of life ( HRQoL ) . Elderly patients with cardiac disease and low exercise capacity are simultaneously the most severely affected and have the most to gain from exercise-based rehabilitation . Individualized combined exercise ( ICE ) may be an effective modality to achieve these goals . We compared six months of ICE to CMP in their effects on LTPA and HRQoL. Methods : Sixty patients ( 70 ± 9 years , 39 % female ) with cardiac disease and low exercise capacity ( were r and omly allocated to six months of once-weekly ICE or CMP . The patients in ICE performed moderate endurance and resistance exercise on machines , based on intensities from individual peak exercise testing . Patients in CMP performed weekly sessions of calisthenics , flexibility , coordination and relaxation activities . LTPA and HRQoL were assessed with accelerometry and question naires at baseline and six months . Results : Sixty patients completed the trial . ICE increased vigorous PA ( ICE : Δ + 12 MET-min/d , CMP : Δ –5 MET-min/d , p = .02 ) and steps per day ( ICE : + 1586 steps/d , CMP : –838 steps/d , p CMP after six months . ICE significantly improved in several components of HRQoL ( vitality , emotional health , social health , positive and negative affect ( all p CMP . Conclusions : ICE result ed in significant improvements in physical activity levels and health related quality of life in moderate to high-risk patients compared to CMP . Implication s for rehabilitation Relatively low volumes and intensities of exercise may lead to substantial improvements in both physical activity levels and health-related quality of life Exercise modes in cardiac rehabilitation maintenance programs should not be limited to calisthenics and large group-based exercise Supplemental resistance exercise may improve health-related quality of life and increase physical activity levels in patients with low exercise capacity Moderate to high-risk elderly patients also benefit from individualized endurance-resistance" ]	41185216-06ff-11f0-808a-c43d1ab1c353
Non-cholesterol sterols are vali date d biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis . However , their use in metabolic disturbances has not been systematic ally explored . Therefore , we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders . Potentially relevant studies were retrieved by a systematic search of three data bases in July 2018 and ninety-four human studies were included . Cholesterol-st and ardized levels of campesterol , sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis . Their use as biomarkers was examined in the following metabolic disorders : overweight/obesity ( n = 16 ) , diabetes mellitus ( n = 15 ) , metabolic syndrome ( n = 5 ) , hyperlipidemia ( n = 11 ) , cardiovascular disease ( n = 17 ) , and diseases related to intestine ( n = 16 ) , liver ( n = 22 ) or kidney ( n = 2 ) . In general , markers for cholesterol absorption and synthesis displayed reciprocal patterns , showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis . Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified , suggesting that metabolic disorders can be classified as ' cholesterol absorbers or cholesterol synthesizers ' . Future studies should be performed to confirm or refute these findings and to examine whether this information can be used for targeted ( dietary ) interventions	[ "BACKGROUND Our aim was to investigate whether intestinal binding of bile acids by guar gum , a dietary fibre , relieves cholestasis and pruritus in intrahepatic cholestasis of pregnancy . METHODS Forty-eight pregnant women with cholestasis and pruritus were r and omized double-blind to guar gum and placebo until the time of delivery , and 20 healthy pregnant women were used as control subjects . The pruritus score and serum bile acids , lipids and non-cholesterol sterols were measured at baseline , at least 2 weeks after treatment , just before delivery and up to 4 weeks after delivery . RESULTS The increase in serum bile acids and worsening of pruritus were prevented by guar gum in relation to placebo ( P Serum cholesterol was unchanged , but increased cholesterol precursor sterol values suggested that cholesterol synthesis was increased by guar gum . Serum cholestanol proportion , an indicator of cholestasis , was related to pruritus but was unaffected by guar gum . CONCLUSION We conclude that in intrahepatic cholestasis of pregnancy and pruritus , guar gum treatment is beneficial in relieving pruritus , even although indicators of cholestasis are only partially reduced", "To assess the validity of two techniques used to measure human cholesterol synthesis , the rate of uptake of deuterium ( D ) into plasma free cholesterol ( FC ) , and plasma cholesterol precursor ( squalene , lanosterol , desmosterol and lathosterol ) levels were compared in 14 women [ 65–71 yr with low density lipoprotein-cholesterol (LDL-C)≥3.36 mmol·l−1 ] . Subjects consumed each of six diets for 5-wk periods according to a r and omized crossover design . The experimental diets included a baseline diet ( 39 % energy as fat , 164 mg chol·4.2 MJ−1 ) and five reduced-fat diets ( 30 % of energy as fat ) , where two-thirds of the fat was either soybean oil ; squeeze , tub or stick margarines ; or butter . Fractional and absolute synthesis rates ( FSR and ASR ) of FC were determined using the deuterium incorporation ( DI ) method , while cholesterol precursor levels were measured using gas-liquid chromatography . Data were pooled across diets for each variable and correlation coefficients were calculated to determine if associations were present . There was good agreement among levels of the various cholesterol precursors . In addition , FSR in pools/d ( p·d−1 ) and ASR in grams/d ( g·d−1 ) were strongly associated with lathosterol ( r=0.72 and 0.71 , P=0.0001 ) , desmosterol ( r=0.75 and 0.75 , P=0.0001 ) , lanosterol ( r=0.67 and 0.67 ) , and squalene ( r=0.69 and 0.68 ) when levels of the precursors were expressed as μmol·mmol−1C . Significant but lower correlations were observed between the D uptake and plasma cholesterol precursor levels when the latter were expressed in absolute amounts ( μmol·L−1 ) . The wide range of fatty acid profiles of the experimental diets did not influence the degree of association between methods . In conclusion , the DI method and levels of some cholesterol precursors correspond as methods for shortterm measurement of cholesterol synthesis", "Background This study is a post-hoc analysis of a subset of patients who participated in our multi-institutional case-control study that evaluated the effects of pitavastatin in patients with non-alcoholic fatty liver disease ( NAFLD ) with hypercholesterolemia . Methods Serum sample s of fifteen patients with biopsy-proven NAFLD with dyslipidemia were investigated . Serum markers of lipid metabolism were quantified by liquid chromatography-mass spectrometry (LC – MS)/MS . These data were then compared with those of 36 sex- and age-matched healthy controls . In addition , changes in these markers produced by treatment with pitavastatin were evaluated . Results Serum non-cholesterol sterols , reflecting intestinal cholesterol absorption , were significantly lower in the NAFLD patients compared to the controls , and the cholesterol synthesis marker , the ratio of lathosterol to cholesterol , was not significantly different between the two groups . Serum proportions of liver X receptor α ( LXRα ) lig and oxysterols ( ratios to cholesterol ) were significantly elevated in the NAFLD patients compared to the controls . The sum of oxysterols relative to cholesterol and the homeostasis model assessment as an index of insulin resistance ( HOMA-IR ) were significantly correlated . The marker representing cholesterol synthesis was significantly suppressed by pitavastatin treatment , from 3 months after initiation of the treatment , and the suppression remained significant during the observation period . The markers representing cholesterol absorption were unchanged at 3 months , but had significantly increased at 12 months . Serum oxysterol levels relative to cholesterol maintained high values and did not change significantly during the 12-month period of treatment . Conclusions : We speculate that serum LXRα lig and oxysterol levels ( relative to cholesterol ) could be surrogate markers of insulin resistance , and that high oxysterol levels in the circulation may play an important role in the development of hepatic and peripheral insulin resistance followed by NAFLD", "BACKGROUND Because of hyperglycemia and hyperinsulinemia , diabetic persons have higher cholesterol synthesis and lower cholesterol absorption rates than do nondiabetic persons . Differences in plant sterol efficacy between diabetic and nondiabetic persons have not been examined . OBJECTIVE The objective was to compare the degree of response of plasma lipid concentrations and glycemic control to plant sterol consumption in a controlled diet between hypercholesterolemic type 2 diabetic and nondiabetic subjects . DESIGN Fifteen nondiabetic subjects and 14 diabetic subjects participated in a double-blinded , r and omized , crossover , placebo-controlled feeding trial . The diet included 1.8 g/d of either plant sterols or cornstarch placebo over 21 d , separated by a 28-d washout period . RESULTS Plant sterol consumption significantly reduced ( P LDL-cholesterol concentrations from baseline in both nondiabetic and diabetic subjects by 15.1 % and 26.8 % , respectively . The diabetic subjects had significantly ( P absolute concentrations of total cholesterol after treatment than did the nondiabetic subjects ; however , there was no significant difference in the percentage change from the beginning to the end of the trial . There was also a significant decrease ( P absolute non-HDL-cholesterol concentrations after treatment in both groups . CONCLUSIONS The results showed that plant sterols are efficacious in lowering LDL cholesterol and non-HDL cholesterol in both diabetic and nondiabetic persons . Plant sterol consumption may exist as a dietary management strategy for hypercholesterolemia in persons with type 2 diabetes", "The physiological roles of phytosterols in chronic inflammation , which are believed to be involved in the underlying mechanisms for metabolic diseases , have yet to be eluci date d. Therefore , in the present study , we aim ed to eluci date the physiological roles of phytosterols in both clinical studies and animal experiments . We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects ( n=46 ) and non-diabetic subjects ( n=178 ) . Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels . When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet , we observed that the increase in body weight , the fatty liver changes , and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake . We also observed that the plasma IL-6 and TNF-α levels , the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6 , TNF-α , and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice . These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases", "Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease . Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients ( either normocholesterolemic or hypercholesterolemic ) with primary biliary cirrhosis and in control subjects . To evaluate cholesterol synthesis , serum levels of lathosterol were measured , and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols . In normocholesterolemic patients with primary biliary cirrhosis , lathosterol was significantly lower than in normocholesterolemic controls ( P Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls ( P patients with primary biliary cirrhosis , serum 7alpha-hydroxycholesterol was slightly higher than in controls . 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls ( P 27-hydroxycholesterol and cholesterol . In contrast , in patients with primary biliary cirrhosis , high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol . Our data confirm that in patients with primary biliary cirrhosis , cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7alpha-hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients . acids via the acidic pathway", "Phytosterol intake with natural foods , a measure of healthy dietary choices , increases plasma levels , but increased plasma phytosterols are believed to be a coronary heart disease ( CHD ) risk factor . To address this paradox , we evaluated baseline risk factors , phytosterol intake , and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) Spanish cohort who developed CHD ( n = 299 ) and matched controls ( n = 584 ) who remained free of CHD after a 10 year follow-up . Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake ( P = 0.026 ) . HDL-cholesterol level increased , and adiposity measures , cholesterol/HDL ratios , and levels of glucose , triglycerides , and lathosterol , a cholesterol synthesis marker , decreased across plasma sitosterol tertiles ( P levels of phytosterol intake and plasma sitosterol . The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 ( 95 % confidence interval , 0.36–0.97 ) . Associations were weaker for plasma campesterol . The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols . The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort , a population with a high phytosterol intake", "Background Gallstone disease ( GD ) has been associated with low serum levels of plant sterols . We evaluated the impact of laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and non-alcoholic fatty liver disease ( NAFLD ) on the association of GD with low levels of serum plant sterols . Methods Two hundred forty-two consecutive morbidly obese patients were recruited to this prospect i ve study . Histological analysis of liver biopsy to diagnose NAFLD was performed . Bile sample was taken during the LRYGB . Associations of GD with serum non-cholesterol sterol to cholesterol ratios , measured using gas liquid chromatography and with mRNA expression of genes participating in the cholesterol , bile , and fatty acid metabolism in the liver , were analyzed . Results Out of the 242 participants , 95 had GD . Lower weight ( p = 0.002 ) and female sex ( p = 0.0006 ) were associated with GD . Serum plant sterols , campesterol ( p = 0.003 ) , sitosterol ( p = 0.002 ) , and avenasterol ( p = 0.015 ) , were lower in patients with GD compared to those without GD . This association remained significant after adjustment for NAFLD , use of statin medication , and previous laparoscopic cholecystectomy ( LCC ) . Levels of sitosterol ( p = 0.001 ) and campesterol ( p = 0.001 ) remained lower in obese individuals with GD also after obesity surgery . Liver mRNA expression of genes regulating cholesterol synthesis and bile metabolism was increased in individuals with GD . Conclusions Serum plant sterols were lower in patients with GD independent of NAFLD , history of LCC , use of statin medication , and weight loss after LRYGB . Low serum plant sterols in patients with GD suggest potentially inherited alterations in sterol absorption and biliary transport in subjects susceptible for GD", "BACKGROUND / AIMS Cholesterol gallstone disease is often associated with an increased biliary secretion rate of cholesterol , which may be due to abnormalities in hepatic cholesterol metabolism . The aim of the present study was to investigate whether gallstone subjects may have an underlying defect in hepatic cholesterol and bile acid formation . METHODS In 41 asymptomatic gallstone subjects , r and omly selected from a population of both sexes 40 and 60 years of age , and in 72 age- and sex-matched controls , plasma levels of lathosterol ( reflecting hepatic HMG CoA reductase activity ) and 7alpha-hydroxy-4-cholesten-3-one ( reflecting cholesterol 7alpha-hydroxylase activity ) were analysed . In a subgroup of gallstone subjects and controls , plasma levels of 27-hydroxy cholesterol were also determined . RESULTS The gallstone subjects had normal plasma levels of cholesterol but displayed 20 - 25 % higher plasma levels of triglycerides compared with the controls . The plasma level of lathosterol was not significantly different between the two groups of subjects whereas the plasma level of 7alpha-hydroxy-4-cholesten-3-one was about 40 % higher in the gallstone subjects compared with the controls . Positive correlations were obtained between plasma levels of 7alpha-hydroxy-4-cholesten-3-one and triglycerides in both groups of subjects . The plasma level of 27-hydroxy cholesterol was similar in gallstone subjects and controls . CONCLUSIONS The previously reported hypersecretion of cholesterol in gallstone patients is not due to a single metabolic defect leading to increased hepatic synthesis of cholesterol or decreased catabolism of cholesterol to bile acids via 7alpha-hydroxylation or 27-hydroxylation of cholesterol", "To investigate the regulation of serum levels of cholesterol precursor sterols and plant sterols , these noncholesterol sterols , fatty acids , and various parameters of cholesterol metabolism were analyzed in 63 volunteers from a r and omly selected Finnish male population sample of 100 subjects , aged 50 years , who had normal dietary habits . Serum levels of cholesterol precursors , desmosterol and lathosterol ( in terms of micrograms/mg cholesterol ) , were negatively related to both the fractional and absolute absorption of dietary cholesterol and serum high density lipoprotein ( HDL ) cholesterol , and positively related to overall cholesterol synthesis and serum very low density lipoprotein ( VLDL ) cholesterol . Serum levels of the plant sterols , campesterol and sitosterol , exhibited positive correlations with the polyunsaturated/saturated fatty acid ratio of dietary fat , the linoleic acid contents of plasma and dietary lipids , the amount of dietary plant sterols ( as indicated by fecal output ) , fractional and absolute absorption of dietary cholesterol , and HDL cholesterol , but were inversely related to the overall cholesterol synthesis and VLDL cholesterol . Stepwise multiple regression analysis revealed that the serum level of campesterol was associated with fractional cholesterol absorption , dietary plant sterols , and biliary cholesterol secretion , and that of sitosterol with dietary plant sterols , cholesterol synthesis , fractional cholesterol absorption , and biliary cholesterol secretion . Thus , the serum non-cholesterol sterols are significant indicators of cholesterol absorption and synthesis even under basal conditions and , since gas liquid chromatographic determination of these sterols is quite simple , their measurement may be valuable for monitoring cholesterol metabolism in large-scale epidemiologic studies", "We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus ( GDM ) . Pregnant women at risk for GDM ( BMI > 30 kg/m2 ) were enrolled from maternity clinics in Finl and . GDM was determined from the results of an oral glucose tolerance test . Serum sample s were collected at six time-points , one in each trimester of pregnancy , and at 6 weeks , 6 months , and 12 months postpartum . Analysis of serum squalene and noncholesterol sterols by gas-liquid chromatography revealed that in subjects with GDM ( n = 22 ) , the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher ( P subjects with GDM had an increased ratio of squalene to cholesterol ( 100 × μmol/mmol of cholesterol ) in the second ( 11.5 ± 0.5 vs. 9.1 ± 0.5 , P maternal serum squalene concentration correlated with neonatal birth weight ( r = 0.70 , P elevated serum markers of cholesterol synthesis . Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM", "To gain further insight into the effects of insulin on cholesterol synthesis in humans , 19 newly insulin-treated diabetic patients were studied before any insulin treatment ( study day 1 ) and after a few days of optimized glycemic control with a continuous intravenous insulin infusion ( study day 2 ) . The patients were divided into two groups according to their clinical characteristics and laboratory disorders . Groups I and II consisted , respectively , of 10 newly diagnosed type I diabetic patients and nine type II diabetic patients with secondary failure to oral antidiabetic drugs . Cholesterol synthesis was estimated from the determination of serum lathosterol , a metabolic precursor in the cholesterol pathway , and from the serum lathosterol to cholesterol ratio . Serum cholesterol ( millimolar , mean + /- SEM ) remained unchanged in both groups . After insulin therapy ( study day 2 ) , serum lathosterol ( micromolar ) and the serum lathosterol to cholesterol ratio ( molar ratio x 10(3 ) ) were significantly increased as compared with baseline ( study day 1 ) . Serum lathosterol levels were as follows : 9.9 + /- 2.0 versus 4.1 + /- 0.4 ( P serum lathosterol to cholesterol ratios were 2.10 + /- 0.39 versus 0.86 + /- 0.11 ( P newly insulin-treated diabetic patients , short-term intensive insulin therapy has a stimulatory effect on cholesterol synthesis and even results in cholesterol overproduction", "Results of previous studies have shown that ezetimibe ( 10 mg/day ) reduces LDL cholesterol in patients with mild hypercholesterolemia on a normal-cholesterol diet ( dietary intake of 200–500 mg/day ) by 16–22 % . However , the LDL cholesterol-lowering effect of ezetimibe in subjects with an extremely low dietary cholesterol intake ( vegetarians ) has not been studied . We conducted a r and omized , double-blind , placebo-controlled , two-phase crossover study in 18 healthy pure vegetarians to assess the effect of ezetimibe ( 10 mg/day ) on plasma lipids , cholesterol absorption , and its synthesis . Treatment periods lasted 2 weeks each , with an intervening 2 week washout period . Fractional cholesterol absorption was determined using the continuous dual stable isotope feeding method . Mean dietary cholesterol intake in the pure vegetarians was extremely low and averaged 29.4 ± 16.8 and 31.4 ± 14.4 mg/day during the placebo and ezetimibe administration phases , respectively . Fractional cholesterol absorption during the placebo phase was 48.2 ± 8.2 % and was decreased by 58 % during ezetimibe treatment to 20.2 ± 6.2 % ( P in intestinal cholesterol absorption was followed by a significant reduction in LDL cholesterol of 17.3 % . In individuals with extremely low dietary cholesterol intake , treatment with ezetimibe ( 10 mg/day ) leads to a significant reduction of cholesterol absorption and a clinical ly relevant decrease of plasma LDL cholesterol , comparable to that of subjects with a normal dietary cholesterol intake . Thus , the lipid-lowering effect of ezetimibe is mediated mainly through a reduction of the absorption of endogenous ( biliary ) cholesterol", "Cholesterol homeostasis , defined as the balance between absorption and synthesis , influences circulating cholesterol concentrations and subsequent coronary heart disease ( CHD ) risk . Statin therapy targets the rate-limiting enzyme in cholesterol bio synthesis and is efficacious in lowering CHD events and mortality . Nonetheless , CHD events still occur in some treated patients . To address differences in outcome during pravastatin therapy ( 40 mg/day ) , plasma markers of cholesterol synthesis ( desmosterol , lathosterol ) and fractional cholesterol absorption ( campesterol , sitosterol ) were measured , baseline and on treatment , in the Prospect i ve Study of Pravastatin in the Elderly at Risk trial participants with ( cases , n = 223 ) and without ( controls , n = 257 ) a CHD event . Pravastatin therapy decreased plasma LDL-cholesterol and triglycerides and increased HDL-cholesterol concentrations to a similar extent in cases and controls . Decreased concentrations of the cholesterol synthesis markers desmosterol ( −12 % and −11 % ) and lathosterol ( −50 % and −56 % ) and increased concentrations of the cholesterol absorption markers campesterol ( 48 % and 51 % ) and sitosterol ( 25 % and 26 % ) were observed on treatment , but the magnitude of change was similar between cases and controls . These data suggest that decreases in cholesterol synthesis in response to pravastatin treatment were accompanied by modest compensatory increases in fractional cholesterol absorption . The magnitude of these alterations were similar between cases and controls and do not explain differences in outcomes with pravastatin treatment", "BACKGROUND The rise in LDL with egg feeding in lean insulin-sensitive ( LIS ) participants is 2- and 3-fold greater than in lean insulin-resistant ( LIR ) and obese insulin-resistant ( OIR ) participants , respectively . OBJECTIVE We determined whether differences in cholesterol absorption , synthesis , or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis . DESIGN Plasma sterols were measured by gas chromatography-mass spectrometry in a r and om subset of 34 LIS , 37 LIR , and 37 OIR participants defined by the insulin sensitivity index ( S(I ) ) and by BMI criteria selected from a parent group of 197 participants . Cholestanol and plant sterols provide a measure of cholesterol absorption , and lathosterol provides a measure of cholesterol synthesis . RESULTS The mean ( ±SD ) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS , 3.25 ± 1.06 in LIR , and 2.82 ± 1.08 in OIR participants . After adjustment for age and sex , the relations of the absorption sterol-cholesterol ratios were as follows : LIS > OIR ( P LIR ( P OIR ( P = 0.11 ) . Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants , 0.95 ± 0.47 in the LIR participants , and 1.29 ± 0.55 in the OIR participants . After adjustment for age and sex , the relations of lathosterol-cholesterol ratios were as follows : LIS ( P = 0.002 ) . Total sterol concentrations were positively associated with S(I ) and negatively associated with obesity , whereas lathosterol correlations were the opposite . CONCLUSIONS Cholesterol absorption was highest in the LIS participants , whereas cholesterol synthesis was highest in the LIR and OIR participants . Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I ) and to decrease cholesterol overproduction in LIR and OIR persons", "Objective : The purpose of this study was to determine whether supplements of plant sterols and /or glucomannan improve lipid profile and cholesterol bio synthesis in mildly hypercholesterolemic type II diabetic and non-diabetic subjects and to compare the response of these two subject groups to the treatments . Design : A r and omized , crossover study consisting of four phases of 21 days , with each phase separated by a 28-day washout . Setting : The Mary Emily Clinical Nutrition Research Unit of McGill University . Subjects : Eighteen non-diabetic individuals and 16 type II diabetic individuals aged 38–74 years . Interventions : Subjects were supplemented with plant sterols ( 1.8 g/day ) , glucomannan ( 10 g/day ) , a combination of glucomannan and plant sterols , and a placebo , provided in the form of bars . Results : Overall plasma cholesterol concentrations were lowered ( P ) . Plasma low-density lipoprotein ( LDL ) cholesterol concentrations were decreased ( P of lipid profiles did not differ between subject groups . Overall plasma lathosterol concentrations , an index of cholesterol bio synthesis , were lowered ( P improves plasma LDL cholesterol concentrations . Sponsorship : Forbes Medi-Tech Inc. , Vancouver , British Columbia , Canada", "To date , there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus ( T2DM ) . In this study , we recruited patients for hypercholesterolemic groups with T2DM ( n = 42 ; men/women = 24/18 ; HbA1c = 6.7 ± 5.4 % ) and without T2DM ( n = 21 ; men/women = 7/14 ; HbA1c = 5.3 ± 0.4 % ) . Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study . At baseline and after 12 weeks of treatment , several lipid parameters , including serum low-density-lipoprotein cholesterol ( LDL-C ) , non-high-density-lipoprotein cholesterol ( non-HDL-C ) , high-sensitivity C-reactive protein ( hs-CRP ) , and cholesterol synthesis /absorption-related markers , were measured . Compared with those at the baseline , the levels of LDL-C , non-HDL-C , campesterol , and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups . After adjusting for confounding factors , such as age , gender , smoking , and BMI , the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM ( -25.1 ± 13.6 % in LDL-C , -20.5 ± 11.2 % in non-HDL-C ) than those without T2DM ( -20.5 ± 7.8 % in LDL-C , P reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM . Taken together , these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM", "BACKGROUND AND AIM Sitosterolemia , a rare genetic disorder characterized by profoundly elevated plasma sitosterol concentrations , is associated with premature atherosclerosis in some individuals . This study was conducted to evaluate if the modest sitosterol elevations seen in the general population are also associated with the occurrence of coronary events . METHODS AND RESULTS A nested case-control study using stored sample s from male participants in the Prospect i ve Cardiovascular Münster ( PROCAM ) study was performed . Each of 159 men who suffered a myocardial infa rct ion or sudden coronary death ( major coronary event ) within 10 years of follow-up in PROCAM was matched with 2 controls ( N = 318 ) by age , smoking status , and date of investigation . Analysis was performed using conditional logistic regression . Plasma sitosterol concentrations were elevated in cases compared with controls ( 4.94 + /- 3.44 micromol/L versus 4.27 + /- 2.38 micromol/L ; P = 0.028 ) . The upper quartile of sitosterol ( > 5.25 micromol/L ) was associated with a 1.8-fold increase in risk ( P men with an absolute coronary risk > or = 20 % in 10 years as calculated using the PROCAM algorithm , high sitosterol concentrations were associated with an additional 3-fold increase in the incidence of coronary events ( P = 0.032 ) ; a similar , significant relationship was observed between a high sitosterol/cholesterol ratio and coronary risk ( P = 0.030 ) . CONCLUSIONS Elevations in sitosterol concentrations and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease . Further evaluations are warranted to confirm these preliminary findings", "Some studies have suggested that a modest increase of plant sterol levels is a risk factor for coronary artery disease ( CAD ) . We studied the relationship between plant sterol levels and CAD risk in a prospect i ve nested case-control study consisting of 373 cases and 758 controls . Sitosterol and campesterol concentrations did not differ between cases and controls [ sitosterol , 0.21 vs. 0.21 mg/dl ( P = 0.1 ) ; campesterol , 0.31 vs. 0.32 mg/dl ( P = 0.5 ) ] . The sitosterol-to-cholesterol ratio was significantly lower in cases than in controls ( 1.19 vs. 1.29 μg/mg ; P = 0.008 ) , whereas the campesterol-to-cholesterol ratio did not differ significantly ( 1.78 vs. 1.88 μg/mg ; P = 0.1 ) . Plant sterol concentrations correlated positively with cholesterol levels and inversely with body mass index and triglyceride and lathosterol concentrations . Among individuals in the highest tertile of the sitosterol concentration , the unadjusted odds ratio ( OR ) for future CAD was 0.75 [ 95 % confidence interval ( CI ) = 0.56–1.01 ] . After adjustment for traditional risk factors , the OR was 0.79 ( 95 % CI = 0.56–1.13 ) . For the campesterol concentration , the unadjusted OR was 0.95 ( 95 % CI = 0.71–1.29 ) and the adjusted OR was 0.97 ( 95 % CI = 0.68–1.39 ) . In this large prospect i ve study , higher levels of plant sterols , at least in the physiological range , do not appear to be adversely related to CAD in apparently healthy individuals", "The differences in cholesterol metabolism after the 2 most common forms of obesity surgery , Roux-en-Y gastric bypass ( RYGB ) and gastric b and ing ( GB ) , have not been well characterized . In this study , effects of RYGB and GB on cholesterol absorption and synthesis were investigated . To this aim , 1-year follow-up of cholesterol metabolism in 2 nonr and omized cohorts undergoing either RYGB ( n = 29 ; age , 45.2 + /- 7.7 years ; body mass index [ BMI ] , 46.0 + /- 6.1 kg/m(2 ) ) or GB ( n = 26 ; age , 45.9 + /- 8.6 years ; BMI , 50.1 + /- 7.7 kg/m(2 ) ) was performed in a university hospital center specializing in the treatment of morbid obesity . Serum markers of cholesterol synthesis ( cholestenol , desmosterol , and lathosterol ) and cholesterol absorption ( campesterol , sitosterol , avenasterol , and cholestanol ) were measured preoperatively and at follow-up and expressed as ratios to cholesterol . As expected based on observed weight loss ( 25 % after RYGB and 17 % after GB , P serum levels of cholesterol synthesis markers by 12 % to 28 % ( all Ps cholesterol absorption markers was only observed after RYGB ( -26 % for sitosterol ) and not after GB ( + 16 % , P = 2 x 10(-6 ) for difference between the groups ) . The difference in sitosterol ratio between the groups remained significant after adjustment for age , BMI , fasting insulin levels , and nutritional status ( P = 2 x 10(-4 ) ) , indicating a specific effect related to RYGB . We conclude that decrease in cholesterol absorption is a novel beneficial effect of RYGB . Together with an improved control of blood glucose , this may contribute to a better cardiovascular risk profile after RYGB" ]	41185298-06ff-11f0-808a-c43d1ab1c353
Trials of the efficacy and safety of vardenafil in the treatment of male erectile dysfunction ( ED ) were meta-analysed . All available data bases were search ed ( January 1 , 2001–November 30 , 2003 ) . Trials were eligible if they included men with ED , compared vardenafil with placebo , were r and omized , were at least of 12 weeks duration , and assessed clinical ly relevant outcomes . Two review ers independently evaluated study quality and extracted data in a st and ardized fashion . Nine trials ( 6809 men ) met the inclusion criteria . In results pooled from seven fixed-dose trials , vardenafil increases the Erectile Function domain of the International Index of Erectile Function question naire by 6.18 units ( weighted mean difference ( WMD ) ) . Vardenafil also increases the percentage of erections firm enough to allow vaginal penetration ( WMD : 26 ) and the percentage of sexual attempts that were successful per participant ( WMD : 29.8 ) . The percentage of men agreeing with the statement that ‘ the treatment they have been taking over the past 4 weeks improved their erections ’ , is also in favour of vardenafil ( relative risk ( RR ) : 3 ) . These efficacy variables appeared greater at higher doses , although there are no significant differences between 10 and 20 mg dose . The same results were extracted for the two flexible ‘ as needed ’ dosing trials . Discontinuations are greater at the vardenafil groups compared to placebo ( RR : 2.25 ) . Specific adverse events with vardenafil included flushing , dyspepsia , headache , and rhinitis . Vardenafil was not significantly associated with serious cardiovascular events or death . Vardenafil , in all treatment regimens , shows to possess superior efficacy to placebo in the treatment of patients with erectile dysfunction . More data is needed on patients ' subgroups	[ "OBJECTIVES To assess whether vardenafil would improve erectile function irrespective of etiology , baseline severity , or patient age . The consistency of the response over time was also evaluated . METHODS A multicenter , r and omized , double-blind , placebo-controlled at-home study of vardenafil treatment ( 5 , 10 , and 20 mg ) was performed . This secondary analysis compared the mean International Index of Erectile Function ( IIEF ) erectile function domain scores of various subgroups at 12 weeks of treatment . These population s included organic , psychogenic , or mixed etiologies ; mild , moderate , or severe baseline severity ; and four age groups ( younger than 45 , 45 to 55 , 56 to 65 , and older than 65 years ) . In addition , all IIEF domains were compared at sequential 4-week periods , before and during treatment . RESULTS In the 580 men of the intent-to-treat population , the mean erectile function domain scores were statistically greater than placebo , irrespective of etiology , baseline severity , or age . This was seen at all dosages . Compared with placebo , vardenafil statistically improved the IIEF domain scores of erectile function , orgasmic function , intercourse satisfaction , and overall satisfaction after 4 weeks of treatment , and these improvements were maintained for 12 weeks . The rates of the most common adverse events ( headache , flushing , and dyspepsia ) were either constant or declined over time ; they were generally mild to moderate and transient in nature . CONCLUSIONS Vardenafil improved erectile function regardless of the general etiology , baseline severity of erectile dysfunction , or patient age . Improvements in erectile function and other key IIEF domains were consistently seen throughout the study", "The aim of the study was to establish and compare the efficacy and safety of sildenafil and apomorphine in men with arteriogenic erectile dysfunction ( ED ) . In all , 43 men with ED and postinjection max penile systolic velocity Of these , 24 men started on apomorphine 2 mg and 19 on sildenafil 50 mg , the doses titrated up to 3 and 100 mg according to effectiveness and tolerability . Safety was evaluated according to adverse events ( AEs ) and patient withdrawal . Efficacy was the percentage of attempts result ing in erections firm enough for intercourse , based on event log data . The incidence of AEs with apomorphine 3 mg was higher than with sildenafil 100 mg . Two men on apomorphine 3 mg discontinued treatment due to AEs . The overall success rate of sildenafil was 63.7 % compared to 32.1 % of apomorphine ( Pearson χ2 , P sildenafil 50 mg without the need for dose increase , while only one responded to apomorphine 2 mg . The response to sildenafil 50 mg was age related ( analysis of variance , p=0.04 ) . Satisfaction was reported by 76.75 and 13.95 % of patients for sildenafil and apomorphine , respectively , but 20.9 % were not satisfied with any of the two drugs . In conclusion , this study provides clear evidence that sildenafil , even at 50 mg dose , is more effective than apomorphine 3 mg in men with arteriogenic ED . The fact that one out of five patients is not satisfied with the above-studied drugs shows that new oral agents need to be evaluated for the treatment of this disorder", "OBJECTIVE This study evaluated the efficacy and safety of vardenafil treatment for erectile dysfunction ( ED ) in men with diabetes . RESEARCH DESIGN AND METHODS In this prospect i ve multicenter double-blind placebo-controlled fixed-dose parallel-group phase III trial , 452 patients with diabetes ( type 1 or type 2 ) and ED were r and omized to take 10 or 20 mg vardenafil or placebo as needed for 12 weeks . Efficacy responses were assessed by International Index of Erectile Function domain scores , rates of vaginal penetration and successful intercourse , and a global assessment question ( GAQ ) about erection improvement during the previous 4 weeks . RESULTS After 12 weeks of treatment , a dose-dependent ( P = 0.02 ) improvement in erections was noted for the GAQ , with 57 and 72 % of men taking 10 mg or 20 mg vardenafil , respectively , reporting improved erections , in contrast to 13 % after taking placebo ( P erectile function domain , dose-dependent ( P = 0.03 ) final scores for the 10- and 20-mg dose were 17.1 and 19.0 compared with 12.6 for placebo ( P rates of successful penetration ( P successful intercourse ( P intercourse success rates at all levels of baseline ED severity , at each level of plasma HbA(1c ) , and for type 1 and 2 diabetes . Treatment-emergent adverse events were primarily mild to moderate headache ( flushing ( rhinitis ( erectile function and was generally well tolerated in these diabetic patients with ED", "Vardenafil , a novel selective phosphodiesterase type 5 inhibitor , was evaluated in its first large-scale at-home trial . A total of 601 men with mild to severe erectile dysfunction ( ED ) were enrolled in this multi-centre , r and omized , double-blind , placebo-controlled trial of 12 weeks of treatment with either placebo or 5 , 10 and 20 mg of vardenafil . Primary endpoints were Q3 ( vaginal penetration ) and Q4 ( maintenance of erection ) of the International Index of Erectile Function ( IIEF ) . In the intent-to-treat population ( n=580 ) , the changes from baseline for 5 , 10 and 20 mg vardenafil ( 1.2 , 1.3 and 1.5 , respectively ) were all improved ( P vardenafil doses improved all IIEF domains compared to placebo ( P percentage of successful intercourses was between 71 and 75 % for the three vardenafil doses . For the 20 mg dose , 80 % of the patients experienced improved erections ( GAQ ) compared to 30 % for placebo . Most frequent treatment-emergent adverse events were headache ( 7–15 % ) , flushing ( 10–11 % ) and up to 7 % for dyspepsia or rhinitis . Vardenafil treatment result ed in a high efficacy and low adverse-event profile in a population with mixed ED etiologies", "Sildenafil ( Viagra , UK-92,480 ) is a novel oral agent under development for the treatment of penile erectile dysfunction . Erection is dependent on nitric oxide and its second messenger , cyclic guanosine monophosphate ( cGMP ) . However , the relative importance of phosphodiesterase ( PDE ) isozymes is not clear . We have identified both cGMP- and cyclic adenosine monophosphate-specific phosphodiesterases ( PDEs ) in human corpora cavernosa in vitro . The main PDE activity in this tissue was due to PDE5 , with PDE2 and 3 also identified . Sildenafil is a selective inhibitor of PDE5 with a mean IC50 of 0.0039 microM. In human volunteers , we have shown sildenafil to have suitable pharmacokinetic and pharmacodynamic properties ( rapid absorption , relatively short half-life , no significant effect on heart rate and blood pressure ) for an oral agent to be taken , as required , prior to sexual activity . Moreover , in a clinical study of 12 patients with erectile dysfunction without an established organic cause , we have shown sildenafil to enhance the erectile response ( duration and rigidity of erection ) to visual sexual stimulation , thus highlighting the important role of PDE5 in human penile erection . Sildenafil holds promise as a new effective oral treatment for penile erectile dysfunction", "OBJECTIVE To assess the efficacy of oral sildenafil in diabetic men with severe erectile dysfunction ( ED ) , who are successfully treated with intracavernous injections of vasoactive drugs . METHODS 81 impotent diabetic men ( 29 with type 1 and 52 with type 2 ) were treated for 1 - 7 years with self-injections . 13 men were treated with 10 microg and 15 with 20 microg of prostagl and in E1 ( PGE1 ) , and 53 with a mixture of PGE1 20 microg and papaverine 7.5 - 40 mg ( MIX ) . After a 1-week washout period , they changed to oral sildenafil in titrating doses up to 100 mg . The change was successful if the man achieved an erection and penetration even once . RESULTS Sildenafil was discontinued in 23 men because of insufficiency . Eleven men ( 13.6 % ) , all with type 2 diabetes , responded to sildenafil ( 10 previously treated with 10 microg and 1 with 20 microg of PGE1 , none treated with MIX ) . Thus , 39.2 % of the treated with PGE1 responded to oral sildenafil . The response was influenced by the age , the type of diabetes ( type 2 ) and the kind of the previously injected drug ( PGE1 10 microg ) ; it was not influenced by the duration of diabetes , ED and treatment with self-injections . CONCLUSIONS Despite the well documented efficacy of sildenafil , self-injections continue to be the solely effective therapeutic modality in many diabetic men afflicted by severe ED . Only the younger men with non-insulin-dependent diabetes , treated with low doses of PGE1 are more likely to respond to oral sildenafil and change treatment . Men with insulin-dependent diabetes or treated with mixtures of vasoactive drugs are not likely to respond to oral sildenafil", "Abstract The pharmacodynamic effect on penile rigidity and tumescence and the pharmacokinetic properties of single oral doses of 10 and 20 mg vardenafil , a new PDE5-inhibitor , were investigated in 21 erectile dysfunction patients . Patients were evaluated with RigiScan on three occasions in a r and omized , placebo-controlled , double-blind crossover fashion , while receiving visual sexual stimulation . Relative to placebo , a single dose of 10 mg vardenafil led to a mean increase in the duration of > 60 % penile rigidity of 24.4 min ( 95 % CI : 7.4 to 41.3 ) at the base and of 24.8 min ( 8.5 to 41.1 ) at the tip . For the 20-mg dose , the increase in duration of > 60 % penile rigidity relative to placebo was 37.2 min ( 20.2 to 54.1 ) at the base and 28.7 min ( 12.7 to 44.7 ) at the tip . Single doses of 10 and 20 mg vardenafil led to a rapid rise in the plasma concentrations of vardenafil , with a median tmax of 0.9 h and 0.7 h and a geometric mean Cmax of 9.1 μg/l ( geometric SD=1.63 ) and 20.9 μg/l ( geometric SD=1.83 ) , respectively . In the post-absorptive phase , the concentrations declined with an average terminal t1/2 of 4.2 h ( geometric SD=1.27 ) and 3.9 h ( geometric SD=1.31 ) . The systemic exposure of vardenafil expressed as AUC normalized for dose and body weight was dose-proportional ( associated 90 % CI : −4 to 30 % ) as well as Cmax ( associated 90 % CI : −12 to 33 % ) . The treatments were well tolerated . There was a small , clinical ly irrelevant reduction in blood pressure with a small compensatory rise in heart rate . There were no electrocardiographic effects or relevant changes of the safety laboratory screens . The observed pro-erectile properties , pharmacokinetic characteristics and safety profile make vardenafil a suitable c and i date for further evaluation in the treatment of erectile dysfunction", "PURPOSE More than one-third of men may experience erectile dysfunction ( ED ) after nerve sparing radical retropubic prostatectomy . The efficacy and safety of vardenafil , a potent , selective , phosphodiesterase 5 inhibitor , was assessed for the treatment of ED after radical prostatectomy . MATERIAL S AND METHODS In this double-blind study 440 men with ED after nerve sparing radical prostatectomy were r and omized to take placebo , or 10 or 20 mg vardenafil . Efficacy was measured after 12 weeks using the erectile function domain of the International Index of Erectile Function , diary questions measuring vaginal penetration and intercourse success rates , and a global assessment question ( GAQ ) on erection . RESULTS Of the intent to treat population 70 % had severe ED ( erectile function less than 11 ) at baseline . After 12 weeks both vardenafil doses were significantly superior to placebo ( p Improved erections ( based on GAQ ) were reported by 65.2 % and 59.4 % of patients on 20 and 10 mg vardenafil , respectively , and by only 12.5 % of patients on placebo ( p positive GAQ responses were reported by 71.1 % and 59.7 % of patients on 20 and 10 mg vardenafil , respectively , versus 11.5 % of those on placebo ( p average intercourse success rate per patient receiving 20 mg vardenafil was 74 % in men with mild to moderate ED and 28 % in men with severe ED , compared to 49 % and 4 % for placebo , respectively . Few adverse events were observed . They were generally mild to moderate headache , flushing and rhinitis . CONCLUSIONS In men with severe ED after nerve sparing radical retropubic prostatectomy , vardenafil significantly improved key indices of erectile function" ]	41185310-06ff-11f0-808a-c43d1ab1c353
IMPORTANCE Bariatric surgery is an accepted treatment for obesity . Despite extensive literature , few studies report long-term follow-up in cohorts with adequate retention rates . OBJECTIVE To assess the quality of evidence and treatment effectiveness 2 years after bariatric procedures for weight loss , type 2 diabetes , hypertension , and hyperlipidemia in severely obese adults . EVIDENCE REVIEW MEDLINE and Cochrane data bases were search ed from 1946 through May 15 , 2014 . Search terms included bariatric surgery , individual bariatric procedures , and obesity . Studies were included if they described outcomes for gastric bypass , gastric b and , or sleeve gastrectomy performed on patients with a body mass index of 35 or greater , had more than 2 years of outcome information , and had follow-up measures for at least 80 % of the initial cohort . Two investigators review ed each study and a third resolved study inclusion disagreements . FINDINGS Of 7371 clinical studies review ed , 29 studies ( 0.4 % , 7971 patients ) met inclusion criteria . All gastric bypass studies ( 6 prospect i ve cohorts , 5 retrospective cohorts ) and sleeve gastrectomy studies ( 2 retrospective cohorts ) had 95 % confidence intervals for the reported mean , median , or both exceeding 50 % excess weight loss . This amount of excess weight loss occurred in 31 % of gastric b and studies ( 9 prospect i ve cohorts , 5 retrospective cohorts ) . The mean sample -size-weighted percentage of excess weight loss for gastric bypass was 65.7 % ( n = 3544 ) vs 45.0 % ( n = 4109 ) for gastric b and . Nine studies measured comorbidity improvement . For type 2 diabetes ( glycated hemoglobin sample -size-weighted remission rates were 66.7 % for gastric bypass ( n = 428 ) and 28.6 % for gastric b and ( n = 96 ) . For hypertension ( blood pressure remission rates were 38.2 % for gastric bypass ( n = 808 ) and 17.4 % for gastric b and ( n = 247 ) . For hyperlipidemia ( cholesterol 40 mg/dL , low-density lipoprotein remission rates were 60.4 % for gastric bypass ( n = 477 ) and 22.7 % for gastric b and ( n = 97 ) . CONCLUSIONS AND RELEVANCE Very few bariatric surgery studies report long-term results with sufficient patient follow-up to minimize biased results . Gastric bypass has better outcomes than gastric b and procedures for long-term weight loss , type 2 diabetes control and remission , hypertension , and hyperlipidemia . Insufficient evidence exists regarding long-term outcomes for gastric sleeve resections	[ "Background : Laparoscopic adjustable gastric b and ing ( LAGB ) and open vertical b and ed gastroplasty ( VBG ) are treatment modalities for morbid obesity . However , few prospect i ve r and omized clinical trials ( RCT ) have been performed to compare both operations . Methods : 100 patients ( 50 per group ) were included in the study . Postoperative outcomes included hospital length of stay ( LOS ) , complications , percent excess weight loss ( % EWL ) , BMI and reduction in total comorbidities . Follow-up in all patients was 2 years . Results : LOS was significantly shorter in the LAGB group . 3 LAGB were converted to open ( 1 to gastric bypass ) . Directly after VBG , 3 patients needed relaparotomies due to leakage , of which one ( 2 % ) died . After 2 years , 100 % follow-up was achieved . BMI and % EWL were significantly decreased in both groups but significantly more in the VBG group compared to the LAGB group ( 31.0 kg/m2 and 70.1 % vs 34.6 and 54.9 % respectively ) . Co-morbidities significantly decreased in both groups in time . 2 years after LAGB , 20 patients needed reoperation for pouch dilation/slippage ( n=12 ) , b and leakage ( n=2 ) , b and erosion ( n=2 ) and access-port problems ( n=4 ) . In the VBG group , 18 patients needed revisional surgery due to staple-line disruption ( n=15 ) , narrow outlet ( n=2 ) or insufficient weight loss ( n=1 ) . Furthermore , 8 VBG patients developed an incisional hernia . Conclusion : This RCT demonstrates that , despite the initial better weight loss in the VBG group , based on complication rates and clinical outcome , LAGB is preferred . It had a shorter LOS and less postoperative morbidity", "Background The objective of this study is to evaluate the long-term outcomes following laparoscopic Roux-en-Y gastric bypass ( LREYGB ) in veteran patients . The VA bariatric population differs from its counterpart in the private sector by the predominance of a male population , a higher percentage of patients from a lower socioeconomic background , a higher mean age , and a higher rate of obesity-related comorbidities . Methods A retrospective review with prospect ively collected data was used to analyze postoperative changes of comorbidities and percent of excess weight loss ( % EWL ) in consecutive patients who underwent LREYGB between August 2003 and September 2006 . Results Among 70 patients , 73 % were men with a mean age of 52 years ( 29–66 years ) . Average preoperative weight and body mass index were 310 lbs ( 224–397 lbs ) and 46 kg/m2 ( 36–60 kg/m2 ) , respectively . The incidence of major and minor complications was 1.4 % and 15.7 % , respectively . There were no mortalities . Follow-up ( f/u ) was possible in all patients . At a mean f/u rate of 39 months , % EWL was 56 % . At 1 , 3 , and 5 years , % EWL was 61 % , 53 % , and 59 % , respectively . Thirty-five patients ( 50 % ) had type 2 diabetes mellitus ( T2DM ) . Glycosylated hemoglobin concentrations returned to normal levels in 91 % of patients and improved in an additional 6 % of T2DM cases . Only 7 % of patients are still maintained on antidiabetic medications . In patients with more than 1 year f/u , most other comorbidities were improved or resolved . Conclusions Long-term f/u of LREYGB in veteran patients demonstrated significant and durable weight loss ( 56 % EWL ) with marked improvements in comorbidities especially T2DM", "to test early nutritional interventions and prospect i ve observational cohorts . RCTs are generally accepted as method ologically the best approach for informing health policy . They can equalise unknown as well as known confounding factors and so can demonstrate causation ; they permit estimation of effect size and so can be used to assess likely", "BACKGROUND Obesity is associated with increased mortality . Weight loss improves cardiovascular risk factors , but no prospect i ve interventional studies have reported whether weight loss decreases overall mortality . In fact , many observational studies suggest that weight reduction is associated with increased mortality . METHODS The prospect i ve , controlled Swedish Obese Subjects study involved 4047 obese subjects . Of these subjects , 2010 underwent bariatric surgery ( surgery group ) and 2037 received conventional treatment ( matched control group ) . We report on overall mortality during an average of 10.9 years of follow-up . At the time of the analysis ( November 1 , 2005 ) , vital status was known for all but three subjects ( follow-up rate , 99.9 % ) . RESULTS The average weight change in control subjects was less than + /-2 % during the period of up to 15 years during which weights were recorded . Maximum weight losses in the surgical subgroups were observed after 1 to 2 years : gastric bypass , 32 % ; vertical-b and ed gastroplasty , 25 % ; and b and ing , 20 % . After 10 years , the weight losses from baseline were stabilized at 25 % , 16 % , and 14 % , respectively . There were 129 deaths in the control group and 101 deaths in the surgery group . The unadjusted overall hazard ratio was 0.76 in the surgery group ( P=0.04 ) , as compared with the control group , and the hazard ratio adjusted for sex , age , and risk factors was 0.71 ( P=0.01 ) . The most common causes of death were myocardial infa rct ion ( control group , 25 subjects ; surgery group , 13 subjects ) and cancer ( control group , 47 ; surgery group , 29 ) . CONCLUSIONS Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality", "The efficacy of three gastric restriction operations were compared in a prospect i ve r and omized study of 310 morbidly obese subjects . The median patient age was 34 years ( range , 18 to 62 years ) . They were predominantly female ( 13:1 ) and had a median pre-operative weight that was 198 % of their ideal weight ( range , 160 % to 318 % ) . There was an equitable dispersion of perceived risk factors between the groups under study and there were no deaths during the perioperative period . Compliance with follow-up at 3 years was 91 % . When success was defined as a loss of more than 50 % of excess weight or a current pregnancy , the success rates at 3 years were 17 % for gastrogastrostomy , 48 % for vertical gastroplasty , and 67 % for Roux-en-Y gastric bypass ( p less than 0.001 ) . Although the gastric bypass operation took longer to perform , there were similar outcome patterns for the three groups during the postoperative period . We conclude that the Roux-en-Y gastric bypass is the preferred procedure for the surgical treatment of morbid obesity", "Background : In the non-superobese population , consensus is currently unavailable in bariatric surgery . We report the results of a prospect i ve comparison of vertical b and ed gastroplasty ( VBG ) and Roux-en-Y gastric bypass ( RYGBP ) in a non-superobese population . Methods : From 1994 to 2000 , 179 patients with clinical ly severe obesity underwent various surgical procedures in our department . During this time a prospect i ve study was undertaken in order to compare VBG with RYGBP in morbidly obese patients with a BMI Based on specific criteria including eating behavior , 68 patients were selected to undergo RYGBP and 35 VBG . All patients have undergone complete follow-up evaluation at 1 , 3 , 6 , and 12 months postoperatively and every year thereafter . Results : All patients have now completed their 5th postoperative year . Mean follow-up period to date is 96.5±12.2 months for VBG and 67.6±11.3 months for RYGBP . 3 patients ( 8.6 % ) in the VBG group and 9 patients ( 13.2 % ) in the RYGBP group are lost to follow-up . Mean excess weight loss ( EWL ) was always better in the RYGBP group ( P=0.0013 ) . The percentage of failure , defined as EWL the total number of non-metabolic complications , and the only statistically significant difference observed in metabolic complications was vitamin B12 deficiency after RYGBP . Frequency of vomiting was significantly less and quality of eating significantly better in RYGBP than in VBG patients . Conclusion : This prospect i ve long-term study , with nearly complete follow-up , suggests that in the non-superobese population , preoperative eating habits may play a role in choosing the most appropriate bariatric operation for each patient . Although RYGBP is associated with better mean weight loss outcomes , the percentage of patients who achieved and maintained ≥50 % EWL after VBG in this pre-selected patient population was not significantly different . Each type of operation has advantages and disadvantages , and , if properly chosen , a purely restrictive procedure can be successful for some patients . Therefore , it can be said that the decision regarding which bariatric procedure to perform in non-superobese patients must be based on in-depth preoperative evaluation as well as the patients ' own preferences and outcome expectations ", "Objective This report documents that the gastric bypass operation provides long-term control for obesity and diabetes . Summary Background Data Obesity and diabetes , both notoriously resistant to medical therapy , continue to be two of our most common and serious diseases . Methods Over the last 14 years , 608 morbidly obese patients underwent gastric bypass , an operation that restricts caloric intake by ( 1 ) reducing the functional stomach to approximately 30 mL , ( 2 ) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet , and ( 3 ) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy . Even though many of the patients were seriously ill , the operation was performed with a perioperative mortality and complication rate of 1.5 % and 8.5 % , respectively . Seventeen of the 608 patients ( Gastric bypass provides durable weight control . Weights fell from a preoperative mean of 304.4 lb ( range , 198 to 615 lb ) to 192.2 lb ( range , 104 to 466 ) by 1 year and were maintained at 205.4 lb ( range , 107 to 512 lb ) at 5 years , 206.5 lb ( 130 to 388 lb ) at 10 years , and 204.7 lb ( 158 to 270 lb ) at 14 years . The operation provides long-term control of non-insulin-dependent diabetes mellitus ( NIDDM ) . In those patients with adequate follow-up , 121 of 146 patients ( 82.9 % ) with NIDDM and 150 of 152 patients ( 98.7 % ) with glucose impairment maintained normal levels of plasma glucose , glycosylated hemoglobin , and insulin . These antidiabetic effects appear to be due primarily to a reduction in caloric intake , suggesting that insulin resistance is a secondary protective effect rather than the initial lesion . In addition to the control of weight and NIDDM , gastric bypass also corrected or alleviated a number of other comorbidities of obesity , including hypertension , sleep apnea , cardiopulmonary failure , arthritis , and infertility", "Background Laparoscopic Roux-en-Y gastric bypass surgery ( RYGB ) was introduced at the authors ’ institution 5 years ago . The authors analyzed the short- and long-term results of this procedure compared with those for the same procedure using the laparotomy approach over the same period . Methods Retrospective analysis of a prospect ively collected bariatric data base used the outcome end points used by the American Society of Bariatric Surgery ( ASBS ) and the American College of Surgeons ( ACS ) in their center of excellence programs . Results From January 2001 to July 2005 , 568 laparoscopic and 399 open gastric bypasses were performed at V and erbilt University . The patients were from the same bariatric surgery program and therefore received the same pre- and postoperative care . The hospital length of stay in the laparoscopic group was significantly shorter ( 2.5 ± 2.4 days ) than in the open group ( 3.7 ± 3.7 days ; p = 0.001 ) . The procedure time was significantly shorter in the laparoscopic group ( 164 ± 50 min ) than in the open group ( 195 ± 50 min ; p = 0.0001 ) . The follow-up assessment response at 2 years was 76.6 % . At 2 years , the excess weight loss ( EWL ) was significantly greater in the laparoscopic group ( 71.3 % ± 18.4 % ) than in the open group ( 67.3 % ± 15.3 % ; p = 0.03 ) . The wound infection rate was significantly higher in open group ( 9.2 % ) than in the laparoscopic group ( 1.7 % ; p = 0.001 ) . There was no significant difference in 30-day mortality : open ( 0.50 % ) versus laparoscopic ( 0.17 % ; p = 0.371 ) . There was no significant difference in the 30-day reoperation rate between the open ( 2.4 % ) and laparoscopic ( 2.6 % ; p = 0.705 ) groups . The 30-day readmission rate was similar in the open ( 5.0 % ) and laparoscopic ( 5.2 % ; p = 0.852 ) groups , as was the rate of leakage from the gastrojejunostomy in the open ( 0.50 % ) and laparoscopic ( 0.35 % ; p = 0.127 ) groups . The conversion rate from laparoscopic procedure to laparotomy was 1.7 % . Conclusion In the authors ’ institution , a laparoscopic bariatric surgery program with a very low rate of morbidity and mortality has been introduced . Operative time , hospital stay , and wound complications are reduced with the laparoscopic approach . The laparoscopic and open procedures are equally safe , with equivalent 30-day mortality , readmission , reoperation , and gastrojejunostomy leakage rates", "Background : Laparoscopic adjustable gastric b and ing ( LAGB ) is a safe and effective method for the treatment of obesity . The most common problem after LAGB has been the occurrence of prolapse ( slippage ) of the stomach through the b and . It has been proposed that the pars flaccida ( PF ) pathway ( dissection from the base of the right crus , along the left crus to the angle of His ) is less likely to be associated with prolapse than the traditional perigastric ( PG ) pathway ( dissection between the lesser curvature of stomach and lesser omentum , across the apex of the lesser sac , to the angle of His ) . We have tested this hypothesis using a r and omized controlled trial format . Methods : We have performed a r and omized controlled trial to compare the outcomes after LAGB using PF and PG pathways . 202 patients ( mean age 40 years , mean weight 123 kg , mean BMI 45 ) were r and omly allocated to the PF or PG pathway and followed for 2 years . Results : At 24 months , there have been 16 revisional procedures for prolapse , 4 in the PF group ( all anterior prolapse ) and 15 in the PG group ( 12 posterior and 3 anterior ) . This difference is significant ( P mean % excess weight lost was 53 % for the PF group and 46 % for the PG group . There was equally significant improvements in the metabolic syndrome in both groups ( 59 % preoperatively and 19 % at 2 years ) . All 8 paired domain scores of the SF-36 measures of quality of life were improved significantly in both group ( P substantial weight loss , improved health and improved quality of life and is significantly less likely to be associated with prolapse ( slippage ) . It is recommended as the primary dissection pathway", "Background : Gastric bypass and adjustable gastric b and ing are the 2 most commonly performed bariatric procedures for the treatment of morbid obesity . The aim of this study was to compare the outcomes , quality of life , and costs of laparoscopic gastric bypass versus laparoscopic gastric b and ing . Study Design : Between 2002 and 2007 , 250 patients with a body mass index of 35 to 60 kg/m2 were r and omly assigned to gastric bypass or gastric b and ing . After exclusion , 111 patients underwent gastric bypass and 86 patients underwent gastric b and ing . Outcome measures included demographic data , operative time , blood loss , length of hospital stay , morbidity , mortality , early and late reoperation rate , weight loss , changes in quality of life , and cost . Treatment failure was defined as losing less than 20 % of excess weight or conversion to another bariatric operation for failure of weight loss . Results : There were no deaths at 90 days in either group . The mean body mass index was higher in the gastric bypass group ( 47.5 vs. 45.5 kg/m2 , respectively , P gastric b and ing , operative blood loss was higher and the mean operative time and length of stay were longer in the gastric bypass group . The 30-day complication rate was higher after gastric bypass ( 21.6 % vs. 7.0 % for gastric b and ) ; however , there were no life-threatening complications such as leaks or sepsis . The most frequent late complication in the gastric bypass group was stricture ( 14.3 % ) . The 1-year mortality was 0.9 % for the gastric bypass group and 0 % for the gastric b and group . The percent of excess weight loss at 4 years was higher in the gastric bypass group ( 68 ± 19 % vs. 45 ± 28 % , respectively , P Treatment failure occurred in 16.7 % of the patients who underwent gastric b and ing and in 0 % of those who underwent gastric bypass , with male gender being a predictive factor for poor weight loss after gastric b and ing . At 1-year postsurgery , quality of life improved in both groups to that of US norms . The total cost was higher for gastric bypass as compared with gastric b and ing procedure ( $ 12,310 vs. $ 10,766 , respectively , P and gastric b and ing are both safe and effective approaches for the treatment of morbid obesity . Gastric bypass result ed in better weight loss at medium- and long-term follow-up but was associated with more perioperative and late complications and a higher 30-day readmission rate . There was a wide variation in weight loss after gastric b and ing with a small proportion of patients considered as treatment failure , and male gender was a predictive factor for poor weight loss", "Background The objective of this study was to study the long-term outcome of adjustable gastric b and ing in the treatment of morbid obesity . In Europe , the preference for gastric b and has declined in favor of Roux-Y-gastric bypass . Methods This is a follow-up of a prospect i ve study on a large cohort of patients after laparoscopic gastric b and ing ( LAGB ) for morbid obesity . Results Complete data were collected on 656 patients ( 88 % ) from a cohort of 745 patients . After a median follow-up of 95 months ( range 60–155 ) , the mean BMI dropped from 41.0 ± 7.3 to 33.2 ± 7.1 kg/m2 , with a 46.2 ± 36.5 % excess weight loss ( EWL ) . A more than 50 % EWL was achieved in 44 % of patients . The b and was still in place in 77.1 % of patients ; conversion to gastric bypass after b and removal was carried out in 98 ( 14.9 % ) patients , while a simple removal was done in only 52 ( 7.9 % ) patients . B and removal was more likely in women and patients with a higher BMI . Conclusions After LAGB , b and removal was necessary for complications or insufficient weight loss in 24 % of patients . Nearly half of the patients achieved a more than 50 % EWL , but in 88 % , a more than 10 % EWL was observed . LAGB can achieve an acceptable weight loss in some patients , but the failure in one out of four patients does not allow proposing it as a first-line option for the treatment of obesity", "Since the last comprehensive review of anticoagulation in acute myocardial infa rct ion four additional r and omized control trials have been reported . The overwhelming majority of all trials favored anticoagulation . Rates of thromboembolism were higher in the control , and hemorrhagic complications in the anticoagulated group . Pooling of all r and omized control trials gives mean case fatality rates of 19.6 % for the control and 15.4 % for the anticoagulated group , a relative reduction of 21 % ( P less than 0.05 or less than 0.001 , depending on the analytic method ) . Five of six r and omized control trials reported \" no effect \" because the difference favoring anticoagulation was not statistically significant . However , sample sizes in these \" negative \" papers were too small to protect against missing a 21 % reduction in true case fatality rate due to anticoagulation ( beta greater than 0.10 ) . All patients who present no specific contraindication should receive anticoagulants during hospitalization for infa rct ion ", "BACKGROUND Evidence of the positive effects of gastric b and ing on patients with diabetes has continued to increase . The long-term follow-up of such patients , however , has been limited . The purpose of the present study was to provide the long-term outcomes of patients with diabetes undergoing laparoscopic adjustable gastric b and ing at our institution . METHODS From January 2002 through June 2004 , 102 patients with type 2 diabetes mellitus underwent laparoscopic adjustable gastric b and ing . The study parameters included preoperative age , gender , race , body mass index , duration of diabetes before surgery , fasting glucose level , hemoglobin A1c ( HbA1c ) , and medications used . Preoperative data from all patients were collected prospect ively and entered into an institutional review board-approved data base . Beginning in 2008 , efforts were made to collect the 5-year follow-up data . RESULTS Of the 102 patients , 7 were excluded because they had not reached the 5-year follow-up point ( 2 patients had had the b and removed early and 5 patients had died ; 2 of cancer and 3 of unknown causes ) , leaving 95 patients for the present study . The mean preoperative age was 49.3 years ( range 21.3 - 68.4 ) . The mean preoperative body mass index was 46.3 kg/m(2 ) ( range 35.1 - 71.9 ) and had decreased to 35.0 kg/m(2 ) ( range 21.1 - 53.7 ) by 5 years of follow-up , yielding a mean percentage of excess weight loss of 48.3 % . The mean duration of the diabetes diagnosis before surgery was 6.5 years . Of 94 patients , 83 ( 88.3 % ) were taking medications preoperatively , with 14.9 % overall taking insulin . At 5 years postoperatively , 33 ( 46.5 % ) of 71 patients were taking medications , with 8.5 % taking insulin . The mean fasting preoperative glucose level was 146.0 mg/dL. The glucose level had decreased to 118.5 mg/dL at 5 years postoperatively ( P = .004 ) . The mean HbA1c level was 7.53 preoperatively in 72 patients and was 6.58 at 5 years postoperatively in 64 patients ( P diabetes had resolved ( no medication requirement , with HbA1c improvement/remission rate was 80 % ( 64 of 80 patients ) . CONCLUSION Our data have demonstrated that laparoscopic adjustable gastric b and ing results in a substantial sustained positive effect on diabetes in morbidly obese patients , with a significant reduction in HbA1c and an 80 % overall rate of improvement/remission", "Objective : The objective of this study was to evaluate the results of laparoscopic gastric b and ing using 2 different b and s ( the Lapb and [ Bioenterics , Carpinteria , CA ] and the SAGB [ Swedish Adjustable Gastric B and ; Obtech Medical , 6310 Zug , Switzerl and ] ) in terms of weight loss and correction of comorbidities , short- and long-term complications , and improvement of quality of life in morbidly obese patients Summary Background Data : During the past 10 years , gastric b and ing has become 1 of the most common bariatric procedures , at least in Europe and Australia . Weight loss can be excellent , but it is not sufficient in a significant proportion of patients , and a number of long-term complications can develop . We hypothesized that the type of b and could be of importance in the outcome . Methods : One hundred eighty morbidly obese patients were r and omly assigned to receive the Lapb and or the SAGB . All the procedures were performed by the same surgeon . The primary end point was weight loss , and secondary end points were correction of comorbidities , early- and long-term complications , importance of food restriction , and improvement of quality of life . Results : Initial weight loss was faster in the Lapb and group , but weight loss was eventually identical in the 2 groups . There was a trend toward more early b and -related complications and more b and infections with the SAGB , but the study had limited power in that respect . Correction of comorbidities , food restriction , long-term complications , and improvement of quality of life were identical . Only 55 % to 60 % of the patients achieved an excess weight loss of at least 50 % in both groups . There was no difference in the incidence of long-term complications . Conclusions : Gastric b and ing can be performed safely with the Lapb and or the SAGB with similar short- and midterm results with respect to weight loss and morbidity . Only 50 % to 60 % of the patients will achieve sufficient weight loss , and close to 10 % at least will develop severe long-term complications", "Background Although the efficacy of laparoscopic sleeve gastrectomy ( LSG ) for morbidly obese patients with a BMI of , the incidence of weight gain by change of eating behaviors , and gastric dilatation following LSG have not been investigated thus far , LSG is becoming more common as a single-stage operation for the treatment morbid obesity . Methods This is a prospect i ve study of the initial 120 patients who underwent isolated LSG . Initially , the LSG was performed without a calibration tube and result ed in high sleeve volumes ( group 1 : n=25 ) . In group 2 ( n=32 ) , a calibration tube of 44 Fr and in group 3 ( n=63 ) a calibration tube of 32 Fr were used . The study group consists of 101 patients with high BMI who were scheduled for a two-step LBPD-DS , but rejected the second step after 1 year . Study endpoints include estimated sleeve volume , volume of removed stomach , operative time , complication rates , length of hospital stay , changes in co-morbidity , percentage of excess BMI loss ( % EBL ) and changes in BMI ( kg/m2 ) . Results All 3 groups were comparable regarding age , gender , and co-morbidities . There was no hospital mortality , but there was one case of late mortality ( 0.8 % ) . 2 early leaks ( 1.7 % ) were seen . % excess BMI loss was significantly higher for patients who underwent LSG with tube calibrations . LSG with large sleeve volume showed a slight weight gain during 5 years of observation . A total of 16 patients ( 13.3 % ) underwent a second stage procedure within a period of 5 years ( 2 redo-sleeves , 7 LBPD-DS , 3 LRYGBP ) . Conclusion Early weight loss results were not different between the groups , but after 2 years the more restrictive LSG ( groups 2 , 3 ) results were significantly better than in patients without calibration . A removed gastric volume of early weight regain . A statistically significant improved health status and quality of life were registered for all groups . The general introduction of LSG as a one-stage restrictive procedure in the bariatric field can be considered only if the procedure is st and ardized and long-term results are available", "CONTEXT Extreme obesity is associated with health and cardiovascular disease risks . Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term , long-term outcomes are uncertain . OBJECTIVE To examine the association of Roux-en-Y gastric bypass ( RYGB ) surgery with weight loss , diabetes mellitus , and other health risks 6 years after surgery . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese ( body mass index [ BMI ] ≥ 35 ) participants aged 18 to 72 years ( 82 % women ; mean BMI , 45.9 ; 95 % CI , 31.2 - 60.6 ) who sought and received RYGB surgery ( n = 418 ) , sought but did not have surgery ( n = 417 ; control group 1 ) , or who were r and omly selected from a population -based sample not seeking weight loss surgery ( n = 321 ; control group 2 ) . MAIN OUTCOME MEASURES Weight loss , diabetes , hypertension , dyslipidemia , and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment . RESULTS Six years after surgery , patients who received RYGB surgery ( with 92.6 % follow-up ) lost 27.7 % ( 95 % CI , 26.6%-28.9 % ) of their initial body weight compared with 0.2 % ( 95 % CI , -1.1 % to 1.4 % ) gain in control group 1 and 0 % ( 95 % CI , -1.2 % to 1.2 % ) in control group 2 . Weight loss maintenance was superior in patients who received RYGB surgery , with 94 % ( 95 % CI , 92%-96 % ) and 76 % ( 95 % CI , 72%-81 % ) of patients receiving RYGB surgery maintaining at least 20 % weight loss 2 and 6 years after surgery , respectively . Diabetes remission rates 6 years after surgery were 62 % ( 95 % CI , 49%-75 % ) in the RYGB surgery group , 8 % ( 95 % CI , 0%-16 % ) in control group 1 , and 6 % ( 95 % CI , 0%-13 % ) in control group 2 , with remission odds ratios ( ORs ) of 16.5 ( 95 % CI , 4.7 - 57.6 ; P incidence of diabetes throughout the course of the study was reduced after RYGB surgery ( 2 % ; 95 % CI , 0%-4 % ; vs 17 % ; 95 % CI , 10%-24 % ; OR , 0.11 ; 95 % CI , 0.04 - 0.34 compared with control group 1 and 15 % ; 95 % CI , 9%-21 % ; OR , 0.21 ; 95 % CI , 0.06 - 0.67 compared with control group 2 ; both P bariatric surgery-related hospitalizations were 33 ( 7.9 % ) , 13 ( 3.9 % ) , and 6 ( 2.0 % ) for the RYGB surgery group and 2 control groups , respectively . CONCLUSION Among severely obese patients , compared with nonsurgical control patients , the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years", "BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline", "BACKGROUND : For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS : We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS : There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS : We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials", "Bariatric surgery ameliorates obesity‐associated diseases , result ing in psychological and social benefits . Long‐term studies of its effects on quality of life ( QOL ) assessed with well established instruments are lacking . This prospect i ve study investigated the long‐term effects of gastric b and ing on health‐related QOL using an obesity‐specific vali date d measure", "Background : Since its introduction about 10 years ago , and because of its encouraging early results regarding weight loss and morbidity , laparoscopic gastric b and ing ( LGB ) has been considered by many as the treatment of choice for morbid obesity . Few long-term studies have been published . We present our results after up to 8 years ( mean 74 months ) of follow-up . Methods : Prospect i ve data of patients who had LGB have been collected since 1995 , with exclusion of the first 30 patients ( learning curve ) . Major late complications are defined as those requiring b and removal ( major reoperation ) , with or without conversion to another procedure . Failure is defined as an excess weight loss ( EWL ) of reoperation . Results : Between June 1997 and June 2003 , LGB was performed in 317 patients , 43 men and 274 women . Mean age was 38 years ( 19 - 69 ) , mean weight was 119 kg ( 79 - 179 ) , and mean BMI was 43.5 kg/m2 ( 34 - 78 ) . 97.8 % of the patients were available for follow-up after 3 years , 88.2 % after 5 years , and 81.5 % after 7 years . Overall , 105 ( 33.1 % ) of the patients developed late complications , including b and erosion in 9.5 % , pouch dilatation/slippage in 6.3 % , and catheter- or port-related problems in 7.6 % . Major reoperation was required in 21.7 % of the patients . The mean EWL at 5 years was 58.5 % in patients with the b and still in place . The failure rate increased from 13.2 % after 18 months to 23.8 % at 3 , 31.5 % at 5 , and 36.9 % at 7 years . Conclusions : LGB appeared promising during the first few years after its introduction , but results worsen over time , despite improvements in the operative technique and material . Only about 60 % of the patients without major complication maintain an acceptable EWL in the long term . Each year adds 3 - 4 % to the major complication rate , which contributes to the total failure rate . With a nearly 40 % 5-year failure rate , and a 43 % 7-year success rate ( EWL > 50 % ) , LGB should no longer be considered as the procedure of choice for obesity . Until reliable selection criteria for patients at low risk for long-term complications are developed , other longer lasting procedures should be used", "Objective : To assess the safety and effectiveness of the laparoscopic sleeve gastrectomy ( LSG ) as compared to the laparoscopic adjustable gastric b and ( LAGB ) , the laparoscopic Roux-en-Y gastric bypass ( LRYGB ) and the open Roux-en-Y gastric bypass ( ORYGB ) for the treatment of obesity and obesity-related diseases . Background : LSG is a newer procedure being done with increasing frequency . However , limited data are currently available comparing LSG to the other established procedures . We present the first prospect i ve , multiinstitutional , nationwide , clinical ly rich , bariatric-specific data comparing sleeve gastrectomy to the adjustable gastric b and , and the gastric bypass . Methods : This is the initial report analyzing data from the American College of Surgeons — Bariatric Surgery Center Network accreditation program , and its prospect i ve , longitudinal , data collection system based on st and ardized definitions and collected by trained data review ers . Univariate and multivariate analyses compare 30-day , 6-month , and 1-year outcomes including morbidity and mortality , readmissions , and reoperations as well as reduction in body mass index ( BMI ) and weight-related comorbidities . Results : One hundred nine hospitals su bmi tted data for 28,616 patients , from July , 2007 to September , 2010 . The LSG has higher risk-adjusted morbidity , readmission and reoperation/intervention rates compared to the LAGB , but lower reoperation/intervention rates compared to the LRYGB and ORYGB . There were no differences in mortality . Reduction in BMI and most of the weight-related comorbidities after the LSG also lies between those of the LAGB and the LRYGB/ORYGB . Conclusion : LSG has morbidity and effectiveness positioned between the LAGB and the LRYGB/ORYGB for data up to 1 year . As obesity is a lifelong disease , longer term comparative effectiveness data are most critical , and are yet to be determined", "Loss to follow-up is problematic in most cohort studies and often leads to bias . Although guidelines suggest acceptable follow-up rates , the authors are unaware of studies that test the validity of these recommendations . The objective of this study was to determine whether the recommended follow-up thresholds of 60–80 % are associated with biased effects in cohort studies . A simulation study was conducted using 1000 computer replications of a cohort of 500 observations . The logistic regression model included a binary exposure and three confounders . Varied correlation structures of the data represented various levels of confounding . Differing levels of loss to follow-up were generated through three mechanisms : missing completely at r and om ( MCAR ) , missing at r and om ( MAR ) and missing not at r and om ( MNAR ) . The authors found no important bias with levels of loss that varied from 5 to 60 % when loss to follow-up was related to MCAR or MAR mechanisms . However , when observations were lost to follow-up based on a MNAR mechanism , the authors found seriously biased estimates of the odds ratios with low levels of loss to follow-up . Loss to follow-up in cohort studies rarely occurs r and omly . Therefore , when planning a cohort study , one should assume that loss to follow-up is MNAR and attempt to achieve the maximum follow-up rate possible", "BACKGROUND The effectiveness and safety of bariatric surgery using laparoscopic adjustable gastric b and s have been demonstrated in numerous published studies . We present the results of the first U.S. multicenter trial of the Realize adjustable gastric b and , a laparoscopic adjustable gastric b and previously available only outside the United States as the Swedish adjustable gastric b and . METHODS A total of 405 morbidly obese patients were screened at 12 different centers from May to November 2003 to participate in a prospect i ve , single-arm study of the safety and effectiveness of the laparoscopically implanted Realize b and . Changes in excess body weight , the parameters of diabetes and dyslipidemia , and the incidence of complications were assessed at 3 years of follow-up . RESULTS Of the 405 patients , 276 ( 78.3 % women and 61.2 % white ) qualified for the study . The average age was 38.6 + or - 9.4 years ( range 18 - 61 ) , and the preoperative body mass index was 44.5 + or - 4.7 kg/m(2 ) . The mean hospital stay was 1.2 + or - 1.3 days . At 3 years , the average excess weight loss was 41.1 % + or - 25.1 % or a decrease in the body mass index of 8.2 kg/m(2 ) ( 18.6 % ) ( P hemoglobin A(1)c level , the level decreased by 1 % ( P total cholesterol , low-density lipoprotein cholesterol , and triglycerides decreased by 9 % , 16 % , and 50 % , respectively ( P high-density lipoprotein cholesterol increased by 25 % ( P 30-day mortality occurred . The complication frequencies were generally low and included esophageal dysmotility in 0.4 % , late balloon failure in 0.4 % , b and erosion in 0.4 % , slippage in 3.3 % , esophageal dilation in 3.3 % , pouch dilation in 3.6 % , catheter kinking in 1.1 % , port displacement in 2.5 % , and port disconnection in 4.3 % . Reoperations were required in 15.2 % of the patients and involved 2 b and replacements , 9 b and revisions , 5 port replacements , 22 port revisions , and 4 explants . CONCLUSION The results of our study have shown that the Realize adjustable gastric b and is safe and effective in a diverse U.S. population of morbidly obese patients . Significant weight loss was achieved throughout the 3 years of follow-up , with corresponding improvements in the indicators of diabetes and dyslipidemia", "BACKGROUND To improve decision making in the treatment of extreme obesity , the risks of bariatric surgical procedures require further characterization . METHODS We performed a prospect i ve , multicenter , observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007 . A composite end point of 30-day major adverse outcomes ( including death ; venous thromboembolism ; percutaneous , endoscopic , or operative reintervention ; and failure to be discharged from the hospital ) was evaluated among patients undergoing first-time bariatric surgery . RESULTS There were 4776 patients who had a first-time bariatric procedure ( mean age , 44.5 years ; 21.1 % men ; 10.9 % nonwhite ; median body-mass index [ the weight in kilograms divided by the square of the height in meters ] , 46.5 ) . More than half had at least two coexisting conditions . A Roux-en-Y gastric bypass was performed in 3412 patients ( with 87.2 % of the procedures performed laparoscopically ) , and laparoscopic adjustable gastric b and ing was performed in 1198 patients ; 166 patients underwent other procedures and were not included in the analysis . The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric b and ing was 0.3 % ; a total of 4.3 % of patients had at least one major adverse outcome . A history of deep-vein thrombosis or pulmonary embolus , a diagnosis of obstructive sleep apnea , and impaired functional status were each independently associated with an increased risk of the composite end point . Extreme values of body-mass index were significantly associated with an increased risk of the composite end point , whereas age , sex , race , ethnic group , and other coexisting conditions were not . CONCLUSIONS The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics . In helping patients make appropriate choices , short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese . ( Clinical Trials.gov number , NCT00433810 ." ]	41185388-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES To establish whether simplified adhesives ( self-etch ) are as clinical ly effective as conventional adhesives ( etch- and -rinse ) with multiple application steps for treatment of non-carious cervical lesions ( NCCLs ) . NULL HYPOTHESIS there is no difference in the clinical effectiveness of the four different bonding strategies : Three-step etch- and -rinse ; Two-step etch- and -rinse ; Two-step self-etch ; One-step self-etch for treatment of NCCLs . SOURCES Electronic data bases were search ed including : Cochrane Oral Health Group Trials Register , the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE and EMBASE . In addition , studies were identified by h and search ing of selected journals . STUDY SELECTION R and omised controlled trials ( RCTs ) comparing at least two adhesives in non-carious cervical lesions ( NCCLs ) , with at least 18 months follow-up were selected . The primary outcome was loss of retention/restoration loss , with marginal adaptation and marginal discolouration as secondary outcomes . Criteria for quality assessment included : r and om sequence generation ; allocation concealment ; blinding of outcome assessment ; and information on withdrawals . Twenty six studies were identified that met the inclusion criteria . In general , studies were not of sufficient quality to fully address the objectives of this review . CONCLUSION There is not enough evidence to support one adhesive or bonding strategy over another for treatment of NCCLs . Consequently , the None hypothesis of no difference can not be supported or rejected with the data currently available . There is a need for better st and ardisation and reporting of r and omised controlled trials investigating adhesive performance . CLINICAL SIGNIFICANCE Studies with low overall risk of bias demonstrated good clinical performance for adhesives with all four bonding strategies . However , included studies showed wide variation between adhesives of the same category	[ "OBJECTIVE This controlled clinical trial evaluated the 5-year clinical performance of a self-etching primer system including selective enamel-etching with phosphoric acid and a one-bottle adhesive system . METHODS Seventy-two non-carious cervical lesions in 8 patients ( 4 male and 4 female ) with a mean age of 61.3 years ( range 45 - 78 ) participated in the study . An enamel bevel was placed and dentin lightly ground , and cavities restored with clearfil liner bond II ( LB ) or single bond ( SB ) in conjunction with a hybrid resin composite ( Clearfil AP-X ) . In the case of 27 cavities for LB , the enamel was pretreated with 37 % phosphoric acid for 10 s. Each patient received both types of restoration , which were distributed on a r and om basis . All restorations ( 37 restorations for LB and 35 restorations for SB ) were placed by one dentist . The restorations were evaluated blind after 5 years using modified USPHS criteria . The data were statistically analyzed using the Fisher 's exact test . RESULTS All but one restoration ( which was replaced by a crown after the 2-year recall ) were evaluated after 5 years . 100 % retention rates were recorded for both restorative groups . No caries was detected in association with any restorations . The only minor problem was marginal discoloration ; superficial and localized marginal discoloration occurred around 18 % of the restorations , and mainly at the dentin margin . There were no significant differences in the marginal integrity between the LB and SB groups . CONCLUSIONS Restorative material s used in this study demonstrated a good clinical effectiveness in the restoration of non-carious cervical lesions for 5 years", "This study evaluated the clinical performance of unprepared Class V resin composites , placed using a self-etching primer and a single-bottle adhesive , over a period of 18 months . Thirty-eight pairs of restorations of Renew hybrid resin composite ( BISCO , Inc ) were placed using adhesives from the same manufacturer in caries-free cervical erosion/abfraction lesions . Based on insensitivity to air , the dentin in 76 % of these lesions was considered to be sclerotic . The restorations were placed without abrasion of tooth surfaces , except for cleaning with plain pumice . One of each pair was placed using Tyrian , a self-etching primer and the other was placed using One-Step , a single-bottle adhesive placed after acid etching . Both the etchant and self-etching primer were applied for 20 seconds . The restorations were clinical ly evaluated at baseline , 6 , 12 and 18 months , using modified Ryge/USPHS criteria . For both adhesives , very low retention of 50 % to 56 % of the restorations was observed over 18 months , leading to the conclusion that tooth surfaces must receive some additional treatment prior to restoration with these adhesives . No statistically significant difference ( p=0.75 ) between the two adhesives was observed in overall performance , and dentinal sclerosis and axial depth did not appear to be important factors in the study", "BACKGROUND A new restorative called a \" giomer composite \" has been introduced . The authors conducted a study to determine retention , anatomical form , caries , staining , marginal discoloration , marginal adaptation , surface roughness and sensitivity of giomer compared with those of a microfilled composite . METHODS The authors placed 40 sets of restorations r and omly in canines and premolars in vivo . They used a giomer composite and a microfilled composite in erosion/abrasion/abfraction Class V lesions that were not altered with rotary instruments . They placed the restorations according to manufacturer 's recommendations , and two calibrated examiners evaluated the restorations independently using modified U.S. Public Health Service criteria at baseline and at six , 18 and 36 months . The lesions receiving the restorations did not differ from each other in the amount of circumferential enamel present , the percentage of the surface area of dentin or lesion type . RESULTS There were no differences in the restorations at baseline , an evaluation made two weeks after placement . At 36 months , the giomer and microfilled composite restorations were not significantly different from one another in any of the eight criteria evaluated . The percentage agreement between examiners was at least 83 percent for each criterion in each evaluation period . CONCLUSIONS Both the giomer and the microfilled composite used in this study meet the clinical portion of the Acceptance Program Guidelines for Dentin and Enamel Adhesives Material s established by the American Dental Association . CLINICAL IMPLICATION S Both the giomer and the microfilled composite used in this study can be used with confidence in Class V lesions", "This r and omized clinical trial compared the performance of an all-in-one adhesive ( iBond ) applied in sclerotic and non-sclerotic non-carious cervical lesions with that of a three-step etch-prime-bond adhesive ( Gluma Solid Bond , SB ) . One-hundred and five lesions were r and omly assigned to four groups according to adhesive , sclerosis scale and technique : 1 ) SB applied to lesions with sclerosis scale 1 and 2 ( n=26 ) ; 2 ) iBond applied to lesions with sclerosis scale 1 and 2 ( n=28 ) ; 3 ) iBond applied to lesions with sclerosis scale 3 and 4 ( n=25 ) and 4 ) iBond applied with prior acid-etching to lesions with sclerosis scale 3 and 4 ( n=26 ) . A microfilled composite ( Durafill VS ) was used as the restorative material . The restorations were evaluated for retention , color match , marginal adaptation , anatomic form , cavosurface margin discoloration , secondary caries , pre- and post-operative sensitivity , surface texture and fracture at insertion ( baseline ) , 6 , 18 months and at 3 years using modified USPHS evaluation criteria ( Alfa = excellent ; Bravo= clinical ly acceptable ; Charlie= clinical ly unacceptable ) . There was a high percentage of Bravo scores for marginal adaptation ( 4%-32 % ) and marginal discoloration ( 18%-60 % ) in Groups 2 , 3 and 4 , but all groups had Charlie scores at 6 months and Charlie scores at 18 months for retention and marginal discoloration , respectively . However , it should be noted that 13 % of the restorations in Group 4 were not retained at three years", "This controlled clinical trial evaluated the 2-year clinical performance of a one-bottle etch- and -rinse adhesive and resin composite system ( Excite/Tetric Ceram ) compared to a resin-modified glass ionomer cement ( RMGIC ) ( Vitremer/3 M ) in non-carious cervical lesions . Seventy cervical restorations ( 35 resin composite - RC- restorations and 35 RMGIC restorations ) were placed by a single operator in 30 patients under rubber dam isolation without mechanical preparation . All restorations were evaluated blindly by 2 independent examiners using the modified USPHS criteria at baseline , and after 6 , 12 and 24 months . Data were analyzed statistically by Fisher 's exact and McNemar tests . After 2 years , 59 out of 70 restorations were evaluated . As much as 78.8 % retention rate was recorded for RC restorations , while 100 % retention was obtained for RMGIC restorations . Fisher 's exact test showed significant differences ( p=0.011 ) for retention . However , there were no significant differences for marginal integrity , marginal discoloration , anatomic form and secondary caries between the RC and RMGIC restorations . The McNemar test detected significant differences for Excite/TC between baseline and the 2-year recall for retention ( p=0.02 ) , marginal integrity ( p=0.002 ) and anatomic form ( p=0.04 ) . Therefore , the one-bottle etch- and -rinse bonding system/resin composite showed an inferior clinical performance compared to the RMGIC", "OBJECTIVES This r and omized controlled clinical trial evaluated the 2-year clinical performance of S3 Bond ( S3 ) and G-Bond ( GB ) in 108 non-carious cervical lesions . METHODS Twenty-three patients , 12 male and 11 female ( mean age : 61.8 years , range : 30 - 79 years ) regularly visiting the Nagasaki University Hospital of Medicine and Dentistry , participated in the study . Each patient received both material s r and omly . All restorations ( 53 restorations for S3 and 55 restorations for GB ) were placed by one dentist . The restorations were blindly evaluated by two examiners at baseline , 6 months , 1 and 2 years using modified USPHS criteria . The data were statistically analyzed using the Cochran Q test and Fisher 's exact test . RESULTS One restoration of each material was lost during 2 years . The only minor clinical problem was the integrity of the enamel margin . Slight marginal staining occurred adjacent to 11 restorations of both S3 and GB . There was no significant difference in the clinical performance between S3 and GB for each variable . CONCLUSIONS Under the protocol used in this study , S3 and GB have demonstrated an acceptable clinical performance up to 2 years", "OBJECTIVE To determine if the results of resin-dentin microtensile bond strength ( μTBS ) is correlated with the outcome parameters of clinical studies on non-retentive Class V restorations . METHODS Resin-dentin μTBS data were obtained from one test center ; the in vitro tests were all performed by the same operator . The μTBS testing was performed 8 h after bonding and after 6 months of storing the specimens in water . Pre-test failures ( PTFs ) of specimens were included in the analysis , attributing them a value of 1MPa . Prospect i ve clinical studies on cervical restorations ( Class V ) with an observation period of at least 18 months were search ed in the literature . The clinical outcome variables were retention loss , marginal discoloration and marginal integrity . Furthermore , an index was formulated to be better able to compare the laboratory and clinical results . Estimates of adhesive effects in a linear mixed model were used to summarize the clinical performance of each adhesive between 12 and 36 months . Spearman correlations between these clinical performances and the μTBS values were calculated subsequently . RESULTS Thirty-six clinical studies with 15 adhesive/restorative systems for which μTBS data were also available were included in the statistical analysis . In general 3-step and 2-step etch- and -rinse systems showed higher bond strength values than the 2-step/3-step self-etching systems , which , however , produced higher values than the 1-step self-etching and the resin modified glass ionomer systems . Prolonged water storage of specimens result ed in a significant decrease of the mean bond strength values in 5 adhesive systems ( Wilcoxon , p μTBS values both after 8 h and 6 months of storage and marginal discoloration ( r=0.54 and r=0.67 , respectively ) . However , the same correlation was not found between μTBS values and the retention rate , clinical index or marginal integrity . SIGNIFICANCE As μTBS data of adhesive systems , especially after water storage for 6 months , showed a good correlation with marginal discoloration in short-term clinical Class V restorations , longitudinal clinical trials should explore whether early marginal staining is predictive for future retention loss in non-carious cervical restorations", "OBJECTIVE To evaluate the performance of All Bond SE used in a one- or two-step protocol in a 24-month r and omized clinical study . METHODS Thirty-three patients with two similarly sized non-carious cervical lesions participated in this study . A total of 66 restorations were placed , half using the one-step All Bond SE protocol ( SE-1 ) and the other half using the two-step All Bond SE protocol ( SE-2 ) . The restorations were evaluated at baseline and after 6 , 12 and 24 months following the modified USPHS criteria and analyzed by the McNemar 's test and Fisher 's exact test ( alpha = 0.05 ) . RESULTS After 24 months , six SE-1 and four SE-2 restorations were rated as Bravo in marginal discoloration The retention rates for SE-1 and SE-2 were 84.8 % and 90.9 % , respectively , after 24 months . Compared to baseline , the retention rate for SE-1 was statistically lower . CONCLUSIONS All Bond SE used in the one- or two-step protocol result ed in high retention rates after 24 months", "OBJECTIVES Flexure at the tooth cervix has been suggested to dislodge cervical restorations more rapidly . The objective of this r and omized controlled clinical trial was to test the hypothesis that a higher composite flexibility better withst and s tooth flexure stress . METHODS One hundred and forty-two non-carious cervical lesions were restored with composites with contrasting stiffness . Seventy-one patients r and omly received two cervical restorations placed following two out of the three experimental groups : ( 1 ) the three-step etch- and -rinse adhesive Permaquick applied with the stiff micro-hybrid composite Amelogen Hybrid ( PMQ/A-Hy , Ultradent ) , ( 2 ) Permaquick applied with the more flexible micro-filled composite Amelogen Microfill ( PMQ/A-Mi , Ultradent ) , or ( 3 ) the ' golden st and ard ' three-step etch- and -rinse adhesive Optibond FL applied with the micro-hybrid composite Prodigy ( O-FL/Pro , Kerr ) . RESULTS The recall rate at 7 years was 80 % . No statistically significant difference was found for any of the parameters evaluated neither between both adhesives , nor between both composites ( McNemar , p>0.05 ) . Eleven percent of the O-FL/Pro restorations were clinical ly unacceptable due to loss of retention ( 5.5 % ) and severe marginal discoloration ( 5.5 % ) . In the PMQ-group , 22 % of the PMQ/A-Mi restorations ( 8 % loss of retention , 5 % severe enamel margin defects , 3 % severe dentin margin defects , 6 % severe marginal discoloration , 3 % extreme sensitivity ) and 19 % of the PMQ/A-Hy restorations ( 13 % loss of retention , 3 % severe enamel margin defects , 3 % severe marginal discoloration ) needed repair or replacement . SIGNIFICANCE The clinical performance of the three adhesive/composite combinations was good and reliable during the 7-year clinical trial . It was concluded that the composite stiffness does not affect the clinical longevity of cervical composite restorations", "UNLABELLED This double-blind r and omized clinical trial compared different ethanol/water and acetone-based systems in non-carious cervical lesions over 36 months . MATERIAL S AND METHODS Eighty-four patients having at least one non-carious cervical lesion [ NCCL ] under occlusion were enrolled in this study . A total of 84 restorations were placed , half for each group ( Adper Single Bond [ SB ] + FiltekA110 or One Step [ OS ] + MicroNew ) . All the material s were placed by two calibrated operators . Two other independent examiners evaluated the restorations at baseline , 6 , 12 , 18 and 36 months , according to slightly modified USPHS criteria . Statistical analysis between material s in each period was conducted using the Fisher 's exact test ( alpha=0.05 ) , and performance of the material s in the baseline in comparison to each period was evaluated by McNemar 's test ( alpha=0.05 ) . RESULTS The 12- , 18- and 36-month retention rates for SB were 95.2 % ( 12 and 18 months ) and 92.3 % ( 36 months ) . For OS , the retention rates were 83.3 % , 73.8 % and 56.4 % , respectively , for each recall period . After 36 months , 10 OS restorations ( 25.7 % ) and seven SB restorations ( 17.9 % ) were rated as Bravo in the marginal discoloration item . CONCLUSIONS The ethanol/water-based adhesive ( Single Bond ) that was evaluated showed a higher retention rate than the acetone-based system ( One Step ) after 36 months of clinical service", "BACKGROUND The authors conducted an in vivo investigation to compare the clinical performance of two commercial one-bottle adhesives and a two-bottle adhesive for restoration of noncarious cervical lesions ( NCCLs ) . METHOD The patient pool consisted of 57 patients and 171 teeth ( three teeth per patient ) , with one NCCL per tooth . Each patient received three resin-based composite restorations , each with a different adhesive : one tooth with a two-bottle , water-based adhesive as the control ; another tooth with a one-bottle , ethanol-based adhesive ; and a third tooth with a one-bottle , solvent-free adhesive . The authors assessed restorations in terms of retention , marginal integrity , margin discoloration and air sensitivity at baseline , six months , one year , two years and three years after initial placement . RESULTS The retention rates at 36 months were 88 percent for the first adhesive , 81 percent for the second adhesive and 90 percent for the third adhesive . No statistically significant differences in retention rates could be shown , with 86 percent of restorations retained overall . Measures of marginal integrity , marginal discoloration and sensitivity also had no statistically significant differences between the three adhesives ( P > .05 ) . CONCLUSIONS All three adhesives performed with acceptable outcomes after a 36-month period , with small differences between the one- and two-bottle systems and between the various solvents . Retention rate was moderately high and air sensitivity was markedly reduced ; however , superficial marginal discoloration and marginal degradation was notable . Certain lesion , tooth and patient characteristics may predispose restorations to retention failure . CLINICAL IMPLICATION S The type of solvent may not be a major factor in retention of Class V restorations in NCCLs . Both single-bottle adhesives and conventional two-bottle adhesives performed acceptably", "Despite the fact that one-step adhesives are currently used routinely in clinical practice , long-term studies on their clinical performance are scarce . The objective of this r and omized controlled clinical trial was to test the hypothesis that a 2-hydroxyethyl methacrylate (HEMA)-free one-step self-etch adhesive performs worse than a conventional multistep etch- and -rinse adhesive . Two-hundred and seventy-six non-carious cervical lesions in 52 patients were restored with a micro-hybrid composite ( Gradia Direct ; GC ) . These restorations were bonded in r and om order either with the HEMA-free one-step adhesive G-Bond ( GC ) or with the ' gold-st and ard ' ( control ) three-step adhesive Optibond FL ( Kerr ) . The restorations were evaluated after 6 , 12 , 24 , and 36 months of clinical service regarding retention , marginal adaptation , microleakage , caries occurrence , and sensitivity . After a medium-long period of 3 yr , similar success in clinical performance was observed for the simplified all-in-one adhesive and the conventional three-step adhesive . However , the one-step adhesive exhibited significantly more incisal marginal defects and discolorations . Whereas marginal degradation appeared to arrest for the multistep etch- and -rinse adhesive after 12 months , the enamel margins of the restorations bonded with the one-step self-etch adhesive continued to deteriorate . These incisal marginal defects were , however , small and could easily be removed by polishing . For both adhesives , large and sclerosed lesions appeared to be at higher risk of retention loss", "While a one-year report had been previously published , this study was undertaken to evaluate the clinical performance and appearance of a resin-modified glass ionomer and a resin composite over two years . Thirty-seven pairs of restorations of FujI II LC and Z 250/Single Bond were placed in caries-free cervical erosion/abfraction lesions without tooth preparation . Restorations were clinical ly evaluated at baseline , 6 , 12 , 18 and 24 months using modified Ryge/USPHS criteria . No statistically significant difference ( p = 0.13 ) was observed in the overall performance of the material s. Retention was 96 % for the resin-modified glass ionomer and 81 % for the resin composite , with no additional restorations of either material lost after one year . As previously reported , retention of the Z 250 restorations at six months was below the minimum specified in the ADA Acceptance Program for Dentin and Enamel Adhesives . The resin composite restorations generally had a better appearance , with a 100 % alpha rating in color match , versus 85 % for the resin-modified glass ionomer", "PURPOSE To investigate the durability of three simplified systems in Class V non-carious abrasion/erosion lesions . METHODS 144 non-carious cervical dentin lesions were restored either with Clearfil Liner Bond 2 , a 2-step self-etching primer ( n = 46 ) , One Coat Bond , a one bottle total-etch system applied with one coat ( n = 46 ) , or Prompt-L-Pop , a 1-step self-etching primer ( \" all-in-one \" ) ( n = 52 ) , in 90 individuals . Ninety-eight of the lesions showed sclerotic dentin and 46 were non-sclerotic . Sixty-one were slightly roughened with a diamond bur before conditioning . The restorations were evaluated every 6 months during a 2-year period with slightly modified USPHS criteria . RESULTS All except three restorations were evaluated over 2 years . The cumulative loss rates for Clearfil Liner Bond 2 , One Coat Bond and Prompt-L-Pop were at 6 months : 4.3 , 2.2 and 3.9 % , at 18 months : 4.3 , 10.9 and 15.4 % and at 24 months : 8.7 , 13.0 and 21.2 % , respectively . The cumulative loss rates of the material s in sclerotic lesions ( 15.7 % ) versus non-sclerotic lesions ( 14.0 % ) were not significanty different . Restorations placed with a diamond bur-roughened lesions showed a loss rate of 14.5 % , while for the non-roughened lesions the frequency was 14.8 %", "PURPOSE This 24-month r and omized paired tooth clinical study evaluated the performance of All Bond 3 used in the simplified ( 2-step ) and full ( 3-step ) versions . METHODS 33 patients , with at least two similar sized non-carious cervical lesions participated in this study . A total of 66 restorations were placed , half using the 2-step All Bond 3 ( AB3 - 2 ) and the other half using 3-step All Bond 3 ( AB3 - 3 ) . The restorations were placed incrementally using the composite resin Aelite . The restorations were evaluated at baseline and after 6 , 12 and 24 months following the modified USPHS criteria . Statistical differences between the adhesive were tested using with McNemar 's test and clinical performance over time for each material with the Fisher 's exact test ( alpha = 0.05 ) . RESULTS After 24 months , six AB3 - 2 and four AB3 - 3 were rated as bravo for marginal discoloration but did not differ from each other significantly ( P > 0.05 ) . The retention rates at 24 months of AB3 - 2 and AB3 - 3 were 90.9 % and 97.0 % , respectively ( P > 0.05 )", "The prime purpose of this clinical trial was to examine the clinical quality and retention rate of resin composite in connection with two recently developed acetone-based primer adhesives in Class V lesions according to ADA Clinical Protocol Guidelines for Dentin and Enamel Adhesive Material s. All cavities were nonretentive and predominantly in dentin ( mixed Class V lesions ) . Total bonding was not limited either by sub-base or by base material s. All the trial restorations were placed under rubber dam . Group 1 ( Version 16 - 135 - 1 ) and group 2 ( Version 17 - 17 - 1 ) consisted of 42 patients with 46 trials and 38 patients with 43 fillings , respectively . The mean follow-up period and the recall response at the end of the study of group 1 were 22.8 months and 92.9 % and of group 2 were 22.4 months and 94.7 % . The trial restorations of both groups maintained their predominantly rated USPHS-Code Alpha level within the follow-up period . The cumulative failure rate of two trials in group 1 and four in group 2 determined a failure percentage of 4.4 % and 9.3 % , respectively , which is within the ADA-18 month limit of Version KL 16 - 135 - 1 came into the market as Prime & Bond(R ) 2.1 , and the other one turned out to be Dyract Adhesive(R ) PSA , which was primarily introduced as a single-component adhesive for compomer restorative Dyract(R ) ( Dentsply DeTrey , Germany )", "PURPOSE To determine the 18-month clinical performance of four tooth-colored restoratives in non-carious cervical lesions . MATERIAL S AND METHODS Buccal abrasion lesions in 83 teeth were restored with each of the following material s : Fuji Cap II , Fuji II LC , APH/Universal Bond 3 , Lite Fil II A/Imperva Bond . Baseline and an 18-month recall was carried out using the Ryge ( USPHS ) method for retention , color match , marginal adaptation , cavosurface marginal discoloration , anatomic form and secondary caries . RESULTS The USPHS results ( % alfa ) for the four products were , respectively : color match ( 9 % , 48 % , 57 % , 55 % ) , marginal discoloration ( 71 % , 76 % , 52 % , 50 % ) , marginal adaptation ( 24 % , 24 % , 33 % , 15 % ) , anatomic form ( 67 % , 86 % , 95 % , 45 % ) and retention ( 100 % , 95 % , 100 % , 65 % ) . Results indicated that ( 1 ) Fuji Cap II exhibited a poor color match at baseline ( 2 ) Color matching of Fuji II LC was comparable to the resin composites and ( 3 ) seven Lite Fil II/Imperva Bond restorations ( 35 % ) were dislodged after 1 1/2 years" ]	4118540a-06ff-11f0-808a-c43d1ab1c353
Objective To establish the clinical relevance of S-carboxymethylcysteine in the treatment of glue ear in children using measures approximating those saving a child from operation for grommet insertion . Data sources Cochrane Library , MEDLINE , EMBASE , PubMed , reference lists and review s were used for r and omised controlled trials comparing S-carboxymethylcysteine with placebo . Seven trials involving 283 children and 146 ears were found . Review methods Studies were r and omised , double-blind comparisons of S-carboxymethylcysteine ( any dose and duration ) with placebo in otitis media with effusion . Quality of trial reporting and validity of methods were assessed and used in sensitivity analysis . Main outcomes were relative benefit and number-needed-to-treat to prevent one grommet operation compared with placebo . Results Successful outcomes were obtained in 17 % of children given placebo ( range 5 % to 38 % in individual studies ) and in 35 % of children given S-carboxymethylcysteine ( range 22 to 80 % ) . For combined data ( children and ears ) the relative benefit was 2.0 ( 95%CI 1.4 to 2.8 ) and number-needed-to-treat 5.5 ( 95 % confidence interval 3.8 to 9.8 ) . Pooled data from trials of higher reporting quality ( 4/7 ) or method ological validity ( 3/7 ) tended to have lower efficacy but were not statistically different from those of lower quality or validity . ConclusionS -carboxymethylcysteine is effective in the treatment of children with glue ear . For every five or six children treated with S-carboxymethylcysteine over one to three months , one will not undergo surgery for grommet insertion who would have done had they been given placebo . The confidence in this conclusion is limited because studies included relatively few children	[ "One hundred and fifty children aged between 2 and 9 years with bilateral SOM were allocated at r and om to three groups : Adeno-tonsillectomy ( 47 cases ) , adenoidectomy ( 47 cases ) and neither procedure ( 53 cases ) . A further 42 children were allocated to either adenoidectomy or no surgery . In all only one ear was treated at r and om by myringotomy and insertion of a ventilation tube . The unoperated ear was examined six weeks , six months , nine months , one , two and three years post-operatively for otoscopic clearance of the effusion , impedance change and improvement in mean hearing threshold . Thus the effects on middle ear status of adenoidectomy alone and in combination with tonsillectomy were assessed . There was a significant clearance of middle ear fluid , change from no peak to peak impedance measurement and hearing gain as a result of both procedures with a late trend favouring the combined operation . Neither pre-operative tonsils size nor the number of attacks of tonsillitis affect outcome . However there is a relationship between age and radiographic post-nasal space airway size with clearance of the effusion one year after surgery . These findings permit recommendation for adenoidectomy with improved expectation for resolution of SOM if cases are selected with reference to these two variables . They also suggest in which cases the operation should not be recommended . Despite the trends in outcome favouring combined operations , the extra morbidity associated with the addition of tonsillectomy does not at present justify recommendation for removal of the tonsils in addition to adenoidectomy for cases with SOM . Tonsillectomy in these children should be assessed on grounds of tonsillar pathology per se and not on the status of the middle ear", "Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size", "BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences", " One hundred and ninety-one children who presented to the author 's clinic with otitis media with effusion ( OME ) over a 2-year period ( 1986 - 1988 ) have been studied prospect ively . Resolution of their OME was considered to have occurred when they had normal findings on pneumatic otoscopy , tympanometry and audiometry on at least two occasions 6 months apart and had subjectively normal hearing in between . The number of operations performed during the course of the disease was used as a surrogate for chronicity . Children with a history of previous aural discharge at presentation were significantly more likely to have chronic OME ( P = < 0.02 )", "As professionals , we want to use the best treatments ; as patients , we want to be given them . Knowing whether an intervention works ( or does not work ) is fundamental to clinical decision making . However , clinical decision making involves more than simply taking published results of research directly to the bedside . Physicians need to consider how similar their patients are to those in the published studies , to take the values and preferences of their patients into account , and to consider their own experience with a given test or treatment . Evidence from clinical research is becoming increasingly important in medical- practice decisions as more and better evidence is published . But when is the evidence strong enough to justify changing a practice ? Individual studies that involve only small numbers of patients may have results that are distorted by the r and om play of chance and thus lead to less than optimal decisions . As is clear from other papers in this series , systematic review s identify , critically appraise , and review all the relevant studies on a clinical question and are more likely to give a valid answer . They use explicit methods and quality st and ards to reduce bias . Their results are the closest we can come to reaching the truth given our current state of knowledge . The questions about an intervention that a systematic review should answer are the following : 1 . Does it work ? 2 . If it works , how well does it work in general and compared with placebo , no treatment , or other interventions that are currently in use ? 3 . Is it safe ? 4 . Will it be safe and effective for my patients ? Whereas the critical appraisal and qualitative synthesis provided by review articles can be interpreted directly , the numerical products of quantitative review s can be more difficult to underst and and apply in daily clinical practice . This paper provides guidance on how to interpret the numerical and statistical results of systematic review s , translate these results into more underst and able terms , and apply them directly to individual patients . Many of these principles can also be used to interpret the numerical results of individual clinical studies . They are particularly relevant to systematic review s , however , because such review s contain more information than do primary studies and often exert greater influence than do individual studies . Making Sense of the Numerical Results of Clinical Studies Although the results of clinical studies can be expressed in intuitively meaningful ways , such results do not always easily translate into clinical decision making . For example , results are frequently expressed in terms of risk , which is an expression of the frequency of a given outcome . ( Risks are probabilities , which can vary between 0.0 and 1.0 . A probability of 0.0 means that the event will never happen , and a probability of 1.0 means that it always happens . ) Consider a hypothetical study of the recurrence of migraine headaches in a control group receiving placebo and a treatment group receiving a new antimigraine preparation , drug M ( a secondary prevention trial ) . Suppose that at the end of the trial , migraines recurred in 30 % of the control group ( the risk for recurrence was 0.30 ) but in only 5 % of the drug M group ( risk of 0.05 ) ( Table 1 ) . Table 1 . Numerical Expression of Hypothetical Clinical Trial Results The outcomes of the study are clear enough for the two groups when they are examined separately . But clinicians and patients are more interested in the comparative results , that is , the outcome in one group relative to the outcome in the other group . This overall ( comparative ) result can be expressed in various ways . For example , the relative risk , which is the risk in the treatment group relative to that in the control group , is simply the ratio of the risks in the two groups . In other words , relative risk is the risk in the treatment group divided by that in the control group , 0.05 0.30 , or 0.17 . The comparison can also be expressed as the reduction in relative risk , which is the ratio between the decrease in risk ( in the treatment group ) and the risk in the control group , 0.25 0.30 , or 0.83 ( Table 1 ) . ( The relative risk reduction can also be calculated as 1 relative risk ) . Although the clinical meaning of relative risk ( and relative risk reduction ) is reasonably clear , relative risk has the distinct disadvantage that a given value ( for example , 0.17 ) is the same whether the risk with treatment decreases from 0.80 to 0.14 , from 0.30 to 0.05 , from 0.001 to 0.00017 , and so forth . The clinical implication s of these changes clearly differ from one another enormously and depend on the specific disease and intervention . An important alternate expression of comparative results , therefore , is the absolute risk reduction . Absolute risk reduction is determined by subtracting the risk in one group from the risk in the other ( for example , the risk in the treatment group is subtracted from the risk in the placebo group ) . In the case of our migraine study , the absolute risk reduction would be 0.30 0.05 , which equals 0.25 , or 25 percentage points . In contrast , for a study in which the risk decreased from 0.001 to 0.00017 , the absolute risk reduction would be only 0.00083 , or 0.083 percentage points , which is a trivial change in comparison ( Table 1 ) . This arithmetic emphasizes the difficulty of expressing the results of clinical studies in meaningful ways . Relative risk and relative risk reduction clearly give a quantitative sense of the effects of an intervention in proportional terms but provide no clue about the size of an effect on an absolute scale . In contrast , although it tells less about proportional effects , absolute risk says a great deal about whether an effect is likely to be clinical ly meaningful . Despite this benefit , even absolute risk is problematic because it is a dimensionless , abstract number ; that is , it lacks a direct connection with the clinical situation in which the patient and physician exist . However , another way of expressing clinical research results can provide that clinical link : the number needed to treat ( NNT ) . Number Needed To Treat The NNT for a given therapy is simply the reciprocal of the absolute risk reduction for that treatment [ 1 , 2 ] . In the case of our hypothetical migraine study ( in which risk decreased from 0.30 without treatment with drug M to 0.05 with treatment with drug M , for a relative risk of 0.17 , a relative risk reduction of 0.83 , and an absolute risk reduction of 0.25 ) , the NNT would be 1 0.25 , or 4 . In concrete clinical terms , an NNT of 4 means that you would need to treat four patients with drug M to prevent migraine from recurring in one patient . To emphasize the difference between the concepts embodied in NNT and relative risk , recall the various situations mentioned above , in all of which the relative risk was 0.17 but in which the absolute risk decreased from 0.80 to 0.14 in one case and from 0.001 to 0.00017 in another . Note that the corresponding NNTs in these two other cases are 1.5 and 1204 , respectively : that is , you would need to treat 1.5 and 1204 patients to obtain a therapeutic result in these two situations compared with 4 patients with drug M ( Table 1 ) . The NNT can be calculated easily and kept as a single numerical reminder of the effectiveness ( or , as we will see , the potential for harm ) of a particular therapy . As we suggested , the NNT has the crucial advantage of direct applicability to clinical practice because it shows the effort that is required to achieve a particular therapeutic target . The NNT has the additional advantage that it can be applied to any beneficial outcome or any adverse event ( when it becomes the number needed to harm [ NNH ] ) . The concept of NNT always refers to a comparison group ( in which patients receive placebo , no treatment , or some other treatment ) , a particular treatment outcome , and a defined period of treatment . In other words , the NNT is the number of patients that you will need to treat with drug or treatment A to achieve an improvement in outcome compared with drug or treatment B for a treatment period of C weeks ( or other unit of time ) . To be fully specified , NNT and NNH must always specify the comparator , the therapeutic outcome , and the duration of treatment that is necessary to achieve the outcome . Important Qualities of the Number Needed To Treat The NNT is treatment specific . It describes the difference between treatment and control in achieving a particular clinical outcome . Table 2 shows NNTs from a selection of systematic review s and large r and omized , controlled trials . Table 2 . Numbers Needed To Treat from Systematic Review s and R and omized , Controlled Trials A very small NNT ( that is , one that approaches 1 ) means that a favorable outcome occurs in nearly every patient who receives the treatment and in few patients in a comparison group . Although NNTs close to 1 are theoretically possible , they are almost never found in practice . However , small NNTs do occur in some therapeutic trials , such as those comparing antibiotics with placebo in the eradication of Helicobacter pylori infection or those examining the use of insecticide for head lice ( Table 2 ) . An NNT of 2 or 3 indicates that a treatment is quite effective . In contrast , such prophylactic interventions as adding aspirin to streptokinase to reduce 5-week vascular mortality rates after myocardial infa rct ion may have NNTs as high as 20 to 40 and still be considered clinical ly effective . Limitations of the Number Needed To Treat Although NNTs are powerful instruments for interpreting clinical effects , they also have important limitations . First , an NNT is generally expressed as a single number , which is known as its point estimate . As with all experimental measurements , however , the true value of the NNT can be higher or lower than the point estimate determined through clinical studies . The 95 % CIs of the NNT are useful in this regard because they provide an indication that", "Overemphasis on hypothesis testing-- and the use of P values to dichotomise significant or non-significant results --has detracted from more useful approaches to interpreting study results , such as estimation and confidence intervals . In medical studies investigators are usually interested in determining the size of difference of a measured outcome between groups , rather than a simple indication of whether or not it is statistically significant . Confidence intervals present a range of values , on the basis of the sample data , in which the population value for such a difference may lie . Some methods of calculating confidence intervals for means and differences between means are given , with similar information for proportions . The paper also gives suggestions for graphical display . Confidence intervals , if appropriate to the type of study , should be used for major findings in both the main text of a paper and its abstract", "This trial was design ed to compare early surgery with watchful waiting for persistent bilateral otitis media with effusion ( OME ) in terms of hearing loss and behavioural problems in pre-school children . A r and omised controlled trial compared the effects of early treatment with ventilation tubes versus watchful waiting for 9 months . Results were analysed by intention-to-treat . One hundred and eighty-two pre-school children ( date of birth between 1 April 1991 and 31 December 1992 ) , mean age of 2.9 years ( SD 0.85 ) with at least a 3-month history of bilateral OME and hearing loss of greater than 25 dB were treated in Bristol Children 's Hospital between November 1993 and January 1996 . Bilateral ventilation tubes were inserted within 6 weeks of r and omisation or within 6 weeks of re assessment after 9 months of watchful waiting , with a final assessment at 18 months . The main outcome measures were behavioural problems , measured by the Richman Behaviour Checklist , and hearing loss at 4000 Hz in the better hearing ear . Early surgical intervention significantly reduced behavioural problems by 17 % ( 95 % CI , 2 % - 33 % ) . This difference was largely mediated by concurrent hearing loss . After 18 months , there was no longer a significant difference ( 95 % Cl , -19 % to + 10 % ) . However , the majority ( 85 % ) of the Watchful Waiting group had required surgery and 22 % of all children still had behavioural problems", "UNLABELLED A recent meta- analysis suggested a possible beneficial effect of carboxymethylcysteine ( Mucodyne ) in resolving otitis media with effusion ( OME ) , but the methodology in several of the included trials was flawed . A double-blind r and omised controlled trial ( RCT ) involving 163 patients ( 78 r and omised to Mucodyne and 85 to placebo ) was therefore performed . MAIN OUTCOME MEASURE operative intervention or not . Of the 28 patients with resolved OME , 17 were in the Mucodyne group and 11 in the placebo group . Although it appeared that patients treated with Mucodyne were 1.68 times more likely to undergo resolution of OME than patients receiving placebo , this did not reach statistical significance . [ Risk ratio of 1.68 ( 95 % C.I. , 0.74 - 3.37 ) ] . chi2 test ( df = 162 ) = 2.24 ( P = 0.134 ) . The absolute risk difference in the study was 8.5 % ( 95 % C.I. , -3 - 20 ) . We can not exclude the possibility that Mucodyne is as beneficial as a 20 % additional resolution of OME , or as harmful as a 3 % decrease in the resolution of OME", "We carried out a double blind comparative trial with placebo serving as control using 250 cases of infant otitis media with effusion ( OME ) in order to objective ly evaluate the clinical usefulness of S-carboxymethylcysteine ( S-CMC ) , an oral mucolytic agent , against OME . The results obtained were as follows . 1 ) Global improvement rate , when judged in items of overall improvement , was 79.8 % in S-CMC group and 58.2 % in placebo group , S group being significantly better when compared to P. 2 ) The degree of improvement in each item for evaluation revealed significantly better results in S group compared to P , in both objective findings of the effusion amount and its property , and in audiological findings . 3 ) Adverse reactions observed in 3 cases ( 2.5 % ) in S group and in 2 ( 1.5 % ) in P group were not serious , and were eliminated through suspension or discontinuation of the medication . The results obtained suggested the usefulness of S-CMC when used in the treatment of OME", "A double-blind placebo controlled trial of Mucodyne ( carbocisteine , Berk Pharmaceuticals ) , Actifed ( triprolidine HC1 and pseudoephedrine HC1 , Wellcome ) and combined Mucodyne and Actifed in the treatment of middle-ear effusions is reported . The trial was undertaken to assess whether either preparation , alone or in combination , would reduce the number of children requiring surgical treatment for this condition . No statistical difference between the various groups in avoiding surgical treatment was detected . In those patients undergoing surgery , pre-operative treatment with Mucodyne was associated with a significantly greater number of ears restored to a normal appearance and middle ear function as measured by tympanometry . All patients relapsing after surgery belonged to the groups receiving placebo , Actifed or the combination of Mucodyne and Actifed prior to the operation" ]	41185fae-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice . OBJECTIVES The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults . SEARCH METHODS We search ed the Cochrane Collaboration Depression , Anxiety and Neurosis review group 's specialised register ( CCDANCTR ) , which includes relevant r and omised controlled trials from the following bibliographic data bases : The Cochrane Library ( all years to April 2011 ) , EMBASE , ( 1980 to July 2011 ) MEDLINE ( 1950 to July 2011 ) and PsycINFO ( 1974 to July 2011 ) . Reference lists of the reports of relevant studies were checked and experts in the field contacted . The review was not limited to English- language articles . SELECTION CRITERIA R and omised controlled trials ( RCTs ) allocating participants with major depression to mirtazapine versus any other antidepressive agent . DATA COLLECTION AND ANALYSIS Two authors independently checked eligibility and extracted data on an intention-to-treat basis . The primary outcome was response to treatment . The secondary outcomes included dropouts and individual adverse events . Meta-analyses were conducted using the r and om-effects model . MAIN RESULTS A total of 29 RCTs ( n = 4974 ) , mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the risk of bias , were included . In comparison with tricyclic antidepressants ( 10 trials , n = 1553 ) there was no robust evidence to detect a difference between mirtazapine and tricyclics in terms of response at two weeks ( odds ratio ( OR ) 0.85 , 95 % confidence interval ( CI ) 0.64 to 1.13 ) or at the end of acute-phase treatment ( at 6 to 12 weeks ) ( OR 0.89 , 95 % CI 0.72 to 1.10 ) . In comparison with selective serotonin reuptake inhibitors ( SSRIs ) ( 12 trials , n = 2626 ) mirtazapine was significantly more effective at two weeks ( OR 1.57 , 95 % CI 1.30 to 1.88 ) and at the end of acute-phase treatment ( OR 1.19 , 95 % CI 1.01 to 1.39 ) . Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor ( venlafaxine only , two trials , n = 415 ) at two weeks ( OR 2.29 , 95 % CI 1.45 to 3.59 ) and at the end of acute-phase treatment ( OR 1.53 , 95 % CI 1.03 to 2.25).In terms of dropouts , there was no robust evidence to detect a difference between mirtazapine and other antidepressants . Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction . AUTHORS ' CONCLUSIONS Some statistically significant and possibly clinical ly meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression . Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment . Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants , although the adverse event profile of mirtazapine is unique	[ "CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data", "& NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine 30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors", "ABSTRACT Objective : This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range ( 50–200 mg/day ) for the treatment of major depressive disorder . Methods : In this multicenter trial , depressed patients ( DSM‑IV defined ; baseline Montgomery – Asberg Depression Rating Scale [ MADRS ] ≥ 22 ) aged 18–80 years were r and omly assigned to 8 weeks of double-blind treatment with escitalopram ( 10 mg/day ) or sertraline ( 50–200 mg/day ) following a 1‑week single-blind placebo lead-in period . There was no placebo comparison arm . Sertraline was initiated at 50 mg/day , and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level . The blind was maintained with matching double-blind placebo capsules for the escitalopram group . Change from baseline to endpoint in MADRS total score ( last observation carried forward ) was the primary efficacy measure . Results : A total of 212 patients received double-blind medication . At week 8 , the mean sertraline dosage was 144 mg/day ( median = 150 mg/day ) . Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups , respectively . At endpoint , 75 % and 70 % of escitalopram- and sertraline-treated patients , respectively , were responders ( ≥ 50 % improvement from baseline in mean MADRS scores ) . Both treatments were generally well tolerated ; only 2 % and 4 % of patients prematurely discontinued escitalopram and sertraline treatment , respectively , due to adverse events . Conclusion : No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50–200 mg/day . At these doses , both escitalopram and sertraline were generally well tolerated", "Background : the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre , r and omized , double-blind , amitriptyline-controlled , 5 week clinical study . Method : 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression ( HPRSD ) score ≥ 18 , were r and omized to treatment with either mirtazapine 20 - 60 mg/day or amitriptyline 75 - 225 mg/day . Results : mirtazapine and amitriptyline were equally effective in reducing depressive symptoms , as assessed by the 17-item HPRSD and MADRS scales . Mirtazapine was better tolerated than amitriptyline , with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial . Conclusion : this study shows that mirtazapine is as effective as amitriptyline in treating major depression , while at the same time better tolerated", "BACKGROUND Previous comparative studies of the selective serotonin reuptake inhibitors ( SSRIs ) have rarely included a placebo control group and have rarely demonstrated significant between-group differences . The study reported on here was a placebo-controlled comparison of the antidepressant effects of two SSRIs , citalopram and sertraline . METHODS Three hundred twenty-three patients with DSM-IV-defined major depressive disorder were r and omized to 24 weeks of double-blind treatment with citalopram ( 20 - 60 mg/day ) , sertraline ( 50 - 150 mg/day ) , or a placebo . The primary efficacy measure was the Hamilton Depression Rating Scale ( HAMD ) and the primary statistical analysis was an analysis of variance comparing the change from baseline to the last observation carried forward in each treatment group . RESULTS Both citalopram and sertraline produced significantly greater improvement than placebo on the HAMD , the Montgomery-Asberg Depression Rating Scale , and the Clinical Global Impression Scale . Significant improvement was observed at earlier timepoints in the citalopram group than the sertraline group ; however , sertraline treatment was associated with increased gastrointestinal side effects and a tendency toward early discontinuation , and analyses that excluded early dropouts revealed similar acute efficacy for the two active treatments . The Hamilton Anxiety Scale demonstrated a significant anxiolytic effect of citalopram , but not sertraline , relative to placebo . CONCLUSIONS This study confirms the antidepressant efficacy of two SSRIs , citalopram and sertraline . It is hypothesized that the more consistent evidence of antidepressant activity that was observed early in treatment in the citalopram group was related to more pronounced antianxiety effects and better tolerability upon initiation of therapy", "OBJECTIVE The objective of this double-blind , multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression . METHODS A total of 241 patients with a diagnosis of moderate depressive disorder ( according to ICD-10 criteria ) were r and omized with either 50 mg sertraline or 612 mg hypericum extract ( hypericum group n = 123 ; sertraline group n = 118 ) . According to the study protocol , 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract ; n = 98 sertraline ) ; 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks . Thus , most patients were treated for a period of 6 months . The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period . RESULTS After the first 12-week treatment period , the HAMD score decreased from almost identical initial values ( 22.0 + /- 1.1 for hypericum and 22.1 + /- 1.1 points for sertraline ) to 8.3 + /- 5.5 points ( hypericum ) and 8.1 + /- 5.6 points ( sertraline ) ( mean + /- SD ) in the patients treated per- protocol ( PP ) population . The statistical test for non-inferiority ( boundary delta = 3 ) revealed that hypericum extract is not inferior to sertraline ( P mean difference between the treatments was 0.1995 points , with a corresponding one-sided 97.5 % confidence interval ( -infinity , 1.3772 ) . In patients who continued treatment in the follow-up phase , the HAMD score at the end of the study was 5.7 + /- 4.8 points ( hypericum group ) and 7.1 + /- 6.3 points ( sertraline group ) . Comparable improvement was also found for the von Zerssen 's Adjective Mood Scale ( BfS ) and CGI during the first and second 12-week treatment period in both treatment groups . With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group , the percentage of patients rated as responders did not differ significantly between treatment groups ( 12 weeks ) . The adverse events of 12 patients in the hypericum group ( 9.8 % ) and of 16 patients in the sertraline group ( 13.6 % ) were possibly related to study medication . No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented . In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as \" good \" or \" very good . \" CONCLUSIONS The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression . These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks", "OBJECTIVE Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase ( 8 weeks ) and an extension phase ( 16 weeks ) . METHODS Patients with major depression and without dementia , at least 65 years old , were eligible ; they were r and omized to mirtazapine or paroxetine once daily , with doses increasing over 42 days . Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale , and tolerability was assessed from adverse events . RESULTS Of 255 patients r and omized , 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis . Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score . Other significant differences were in the proportion of patients classified as responders ( 50 % decrease from baseline Ham-D-17 scores ) at Day 14 and in remission ( Ham-D-17 score of 7 or less ) at Day 42 . The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group . The mirtazapine group also showed more reduction in Ham-D Factor I ( Anxiety/Somatization ) and Factor VI ( Sleep Disturbance ) scores . Efficacy of both drugs was maintained during the extension phase . Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events . CONCLUSION During the first weeks of treatment , antidepressant effects were more pronounced in the mirtazapine group , suggesting that mirtazapine has an earlier onset of action . Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients", "A national survey was administered to determine 1 ) cardiovascular physicians ' beliefs about the association between depression and cardiovascular disease ( CVD ) , 2 ) the methods used to diagnose depression , 3 ) referral patterns for treatment of depression , and 4 ) frequency of use and preferred choice of antidepressant . A national survey of 50 % of r and omly selected U.S. cardiovascular physicians belonging to the American College of Cardiology was conducted ; 796 of 8854 physicians who received the question naires responded . Cardiovascular physicians were aware of indirect associations between depression and coronary artery disease ( CAD ) . However , 49.9 % were unaware of depression as an independent cardiac risk factor ; 71.2 % asked less than half their patients with CAD about depression ; 79 % used no st and ard screening method to diagnose depression . Among cardiovascular physicians , 84.8 % reported that between 1 % and 50 % of their patients have depression , and 49.2 % indicated that they treat the symptoms of depression in their patients with CAD . Cardiovascular physicians often refer depressed patients with CAD to mental health professionals and recommend exercise , relaxation training , stress management , psychotherapy , and diaries for their patients . Among cardiovascular physicians , 55.5 % treat depression/CAD with antidepressant medication : sertraline ( 28 % ) , paroxetine ( 16.1 % ) , fluoxetine ( 10.8 % ) , escitalopram ( 8.7 % ) , citalopram ( 7.9 % ) , bupropion ( 4.4 % ) , tricyclic antidepressants ( 3.8 % ) , and venlafaxine 2.9 %", "CONTEXT Extracts of Hypericum perforatum ( St John 's wort ) are widely used for the treatment of depression of varying severity . Their efficacy in major depressive disorder , however , has not been conclusively demonstrated . OBJECTIVE To test the efficacy and safety of a well-characterized H perforatum extract ( LI-160 ) in major depressive disorder . DESIGN AND SETTING Double-blind , r and omized , placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States . PARTICIPANTS Adult out patients ( n = 340 ) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale ( HAM-D ) of at least 20 . INTERVENTIONS Patients were r and omly assigned to receive H perforatum , placebo , or sertraline ( as an active comparator ) for 8 weeks . Based on clinical response , the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg . Responders at week 8 could continue blinded treatment for another 18 weeks . MAIN OUTCOME MEASURES Change in the HAM-D total score from baseline to 8 weeks ; rates of full response , determined by the HAM-D and Clinical Global Impressions ( CGI ) scores . RESULTS On the 2 primary outcome measures , neither sertraline nor H perforatum was significantly different from placebo . The r and om regression parameter estimate for mean ( SE ) change in HAM-D total score from baseline to week 8 ( with a greater decline indicating more improvement ) was -9.20 ( 0.67 ) ( 95 % confidence interval [ CI ] , -10.51 to -7.89 ) for placebo vs -8.68 ( 0.68 ) ( 95 % CI , -10.01 to -7.35 ) for H perforatum ( P = .59 ) and -10.53 ( 0.72 ) ( 95 % CI , -11.94 to -9.12 ) for sertraline ( P = .18 ) . Full response occurred in 31.9 % of the placebo-treated patients vs 23.9 % of the H perforatum-treated patients ( P = .21 ) and 24.8 % of sertraline-treated patients ( P = .26 ) . Sertraline was better than placebo on the CGI improvement scale ( P = .02 ) , which was a secondary measure in this study . Adverse-effect profiles for H perforatum and sertraline differed relative to placebo . CONCLUSION This study fails to support the efficacy of H perforatum in moderately severe major depression . The result may be due to low assay sensitivity of the trial , but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy", "CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion", "BACKGROUND The efficacy , tolerability , and effects on sexual function and satisfaction of nefazodone and sertraline were compared in a multicenter , r and omized , double-blind , parallel-group study in out patients with major depression . METHOD One hundred sixty patients , 18 years of age or older , who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episodes were r and omly assigned to 6 weeks of treatment with either nefazodone ( 100 - 600 mg/day ) or sertraline ( 50 - 200 mg/day ) . Symptoms were assessed before and during treatment using the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , Clinical Global Impressions ( CGI ) Improvement scale , the CGI Severity of Illness scale , and a sexual function question naire . RESULTS Of 143 patients evaluable for efficacy , 72 received sertraline and 71 received nefazodone . The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone . Analysis of efficacy measures ( HAM-D-17 and CGI ) showed consistent and comparable improvement in symptoms of depression for both treatment groups . Sertraline had negative effects on sexual function and satisfaction in both men and women , and nefazodone had no adverse effect on sexual well-being . Safety assessment s based on adverse events , vital sign measurements , electrocardiographs , physical examinations , and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration . CONCLUSION Nefazodone and sertraline are well tolerated , and there was no statistically significant difference in their antidepressant activity . Sertraline treatment has negative effects on sexual function and performance in both sexes , while nefazodone has none . These findings may have clinical implication s when choosing antidepressant therapy", "One hundred and ninety-seven out patients with atypical depression [ Atypical Depression Diagnostic Scale ( ADDS ) score=4 ] were r and omized to 12 weeks of double-blind treatment with sertraline or moclobemide in a multicentre , parallel-group clinical trial . Patients were started on either 50 mg/day sertraline or 300 mg/day moclobemide . If the therapeutic response was not satisfactoryafter 4 weeks , the dose could be increased to either 100 mg/day sertraline or 450 mg/day moclobemide . Primary effcacy evaluations were the 29-item Hamilton Psychiatric Rating Scale for Depression ( HAM-D ) and the Clinical Global Impression of Improvement ( CGI I ) response rate ( much or very much improved ) at study endpoint . Secondary effcacy evaluations included the ADDS , the Hamilton Anxiety Scale ( HAMA ) , the Leeds Sleep Scale , and the Battelle Quality of Life Battery ( BQOLB ) . In the analysis of the 172 patient effcacy-evaluable population , there was significant baseline to endpoint improvement in all primary and secondary effcacy assessment s after treatment with either sertraline or moclobemide . At the endpoint , the proportion of responders on CGI-I , was 77.5 % in the sertraline group and 67.5 % in the moclobemide group ( p=0.052 ) . The baseline to endpoint mean 29-item HAM-D score decreased from 35.9 to 14.5 in the sertraline group and from 36.3 to 16.1 in the moclobemide group . Sertraline also result ed in a significantly ( p50.05 ) greater degree of improvement at the endpoint , compared with moclobemide , in the proportion of remitters on the HAMA ( total score47 ) , ADDS Category IID ( Rejection Sensitivity ) , Leeds Sleep Factor 4 ( Integrity of Behaviour Following Awakening ) , and on three dimensions of the BQOLB ( Energy/Vitality , Social Interaction and Life Satisfaction ) . There were no other significant differences between treatment groups . Overall , both medications were well tolerated . In this study , both sertraline and moclobemide improved the symptoms of atypical depression", "We employed a study design that permitted a double-blind 12-week contrast of imipramine hydrochloride and phenelzine sulfate therapies in patients who met Columbia University criteria for atypical depression and were unresponsive to 7 weeks of treatment with placebo . These patients were found to benefit selectively from therapy with monoamine oxidase inhibitors compared with tricyclic drug therapy . This supports our observation about treatment response in depressed patients with reversed vegetative features . The design we utilized in this study has not previously been reported , to our knowledge . It was hypothesized that it would offer the advantage of the removal of a portion of placebo responders and serve to replicate our original findings . Treatment response to therapy with both imipramine and pheneizine in placebo nonresponders was uniformly lower ( roughly 20 % less than corresponding rates for patients who did not participate in the initial 6-week placebo trial ) . This is consistent with the view that the lower response rates were a result of the removal of some \" placebo \" responders in the drug groups . We think this is a useful design that should be considered in all studies of placebo and two active treatment regimens", "OBJECTIVE Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors ( SNRIs ) ; however , it has been tested against an SNRI in only 1 previous study , and never at an optimal dose . The objective of the current multisite study was to compare relatively higher doses of sertraline ( i.e. , 150 mg/day ) and venlafaxine extended release ( XR ) ( 225 mg/day ) in out patients with major depressive disorder . METHOD Subjects with DSM-IV major depressive disorder were r and omly assigned to 8 weeks of double-blind treatment with sertraline ( N = 82 ) or venlafaxine XR ( N = 78 ) . The study ran from January 2002 through January 2003 . The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Question naire ; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression . RESULTS Both treatments led to significant improvement in depressive symptoms and quality -of-life measures . No significant differences were noted between treatment groups for final scores on the primary or secondary measures . The treatment groups did not differ significantly in the percentage of responders ( sertraline = 55 % , venlafaxine XR = 65 % ; intent-to-treat [ ITT ] sample ) or remitters ( sertra-line = 38 % , venlafaxine XR = 49 % ; ITT sample ) , although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor ( SSRI ) vs. venlafaxine meta-analyses . In patients who achieved the maximum dose of drug and maintained it for 3 weeks , response rates were similar to those found at lower doses ( sertraline = 59 % , venlafaxine XR = 70 % ) ; however , remission rates for this sample were comparable for both drug groups ( sertraline = 48 % , venlafaxine XR = 50 % ) . CONCLUSIONS The efficacies of sertraline and venlafaxine XR were comparable . Although response and remission rates did not differ statistically , the rates were analogous to those reported in previous meta-analyses . However , at clinical ly relevant higher doses , the remission rates were very similar . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00179283", "BACKGROUND The \" long/short\"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action", "BACKGROUND The comparative efficacy of selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) was recently debated . Meta-analyses , based mainly on fluoxetine comparator data , suggest that the SNRI venlafaxine has superior efficacy to SSRIs in treatment of major depression . OBJECTIVE To compare quality of life ( QOL ) , efficacy , safety , and tolerability associated with sertraline and venlafaxine extended release ( XR ) for treatment of DSM-IV major depression . METHOD This was an 8-week , double-blind , r and omized study of sertraline ( 50 - 150 mg/day ) versus venlafaxine XR ( 75 - 225 mg/day ) , followed by a 2-week taper period . Subjects were recruited from 7 sites in Turkey and 6 sites in Australia between October 2002 and July 2003 . The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Question naire . Secondary outcome measures included measures of depression ( including response and remission ) , anxiety , pain , safety ( e.g. , blood pressure ) , and tolerability ( e.g. , discontinuation symptoms ) . RESULTS A total of 163 subjects received study treatment ( women , 69 % ; mean age , 37.0 [ SD = 12.9 ] years ) . No significant differences in QOL or efficacy were noted between treatments on the primary or secondary endpoints for the total study population or the anxious depression and severe depression subgroups . A priori analyses of symptoms associated with treatment discontinuation demonstrated no difference between treatment groups . However , in post hoc analyses , sertraline was associated with less burden of moderate to severe discontinuation symptoms . Venlafaxine XR was associated with a relative increase in mean blood pressure ( supine diastolic blood pressure , -4.4 mm Hg difference at week 8/last observation carried forward ) . CONCLUSION Sertraline and venlafaxine XR demonstrated comparable effects on QOL and efficacy in treatment of major depression , although sertraline may be associated with a lower symptom burden during treatment discontinuation and a reduced risk of blood pressure increase", "CONTEXT Few r and omized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease ( CAD ) . None have simultaneously evaluated an antidepressant and short-term psychotherapy . OBJECTIVE To document the short-term efficacy of a selective serotonin reuptake inhibitor ( citalopram ) and interpersonal psychotherapy ( IPT ) in reducing depressive symptoms in patients with CAD and major depression . DESIGN , SETTING , AND PARTICIPANTS The Canadian Cardiac R and omized Evaluation of Antidepressant and Psychotherapy Efficacy , a r and omized , controlled , 12-week , parallel-group , 2 x 2 factorial trial conducted May 1 , 2002 , to March 20 , 2006 , among 284 patients with CAD from 9 Canadian academic centers . All patients met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for diagnosis of major depression of 4 weeks ' duration or longer and had baseline 24-item Hamilton Depression Rating Scale ( HAM-D ) scores of 20 or higher . INTERVENTIONS Participants underwent 2 separate r and omizations : ( 1 ) to receive 12 weekly sessions of IPT plus clinical management ( n = 142 ) or clinical management only ( n = 142 ) and ( 2 ) to receive 12 weeks of citalopram , 20 to 40 mg/d ( n = 142 ) , or matching placebo ( n = 142 ) . MAIN OUTCOME MEASURES The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D , administered blindly during central ized telephone interviews ( tested at alpha = .033 ) ; the secondary outcome measure was self-reported Beck Depression Inventory II ( BDI-II ) score ( tested at alpha = .017 ) . RESULTS Citalopram was superior to placebo in reducing 12-week HAM-D scores ( mean difference , 3.3 points ; 96.7 % confidence interval [ CI ] , 0.80 - 5.85 ; P = .005 ) , with a small to medium effect size of 0.33 . Mean HAM-D response ( 52.8 % vs 40.1 % ; P = .03 ) and remission rates ( 35.9 % vs 22.5 % ; P = .01 ) and the reduction in BDI-II scores ( difference , 3.6 points ; 98.3 % CI , 0.58 - 6.64 ; P = .005 ; effect size = 0.33 ) also favored citalopram . There was no evidence of a benefit of IPT over clinical management , with the mean HAM-D difference favoring clinical management ( -2.26 points ; 96.7 % CI , -4.78 to 0.27 ; P = .06 ; effect size , 0.23 ) . The difference on the BDI-II did not favor clinical management ( 1.13 points ; 98.3 % CI , -1.90 to 4.16 ; P = .37 ; effect size = 0.11 ) . CONCLUSIONS This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management . Based on these results and those of previous trials , citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N15858091", "OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in \" real world \" patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care \" real world \" setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results", "BACKGROUND Hypericum ( St. John 's wort ) has been shown to be as efficacious and well tolerated as st and ard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors ( SSRIs ) . OBJECTIVE This study compared hypericum and the SSRI sertraline in the treatment of depression . METHODS In a double-blind , r and omized study conducted in a community hospital , 30 male and female out patients ( 19 women , 11 men ; mean age , 45.5 years ) with mild to moderate depression received 600 mg/d of a st and ardized extract of hypericum ( LI 160 ) or 50 mg/d sertraline for I week , followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks . RESULTS The severity of symptoms , as assessed by scores on the Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impression scale , was significantly reduced in both treatment groups ( P or = 50 % reduction in HAM-D scores ) was noted in 47 % of patients receiving hypericum and 40 % of those receiving sertraline . The difference was not statistically significant . Both agents were well tolerated . A post hoc power analysis indicated that failure to reach statistical significance between treatments result ed primarily from an absence of clinical differences rather than the small sample size . CONCLUSION The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of out patients", "In this cross-sectional study we explored in 101 depressive in- patients ( DSM III-R ) the association between level of trait anxiety and variables that have been investigated previously to discern primary and secondary depression , respectively . Besides , we explored the influence of trait anxiety level on difference in treatment response to either imipramine or mirtazapine . Trait anxiety was measured interviewing a close relative of the patient using a question naire related to aspects of psychic anxiety and to aspects of somatic anxiety . The interviewer focussed on fluctuating anxiety symptoms without persistent mood disturbance during the patient 's normal lifelong functioning before developing a depressed mood . We found no relation between trait anxiety level and treatment response to either imipramine or mirtazapine . The most important finding of this study is the significant differential response to the diazepam test : depressive patients with high trait anxiety showed , predominantly , a disappearance of depressive symptoms without sedation and depressive patients with low trait anxiety showed , predominantly , sedation without disappearance of depressive symptoms . The opposite response to the diazepam test in patients with a different history of trait anxiety in spite of similar depressive symptomatology suggests differences in underlying pathophysiologic mechanisms", "This study assessed whether fluoxetine , sertraline , and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes . Patients ( N = 284 ) with DSM-IV major depressive disorder were r and omly assigned in a double-blind fashion to fluoxetine , paroxetine , or sertraline for 10 to 16 weeks of treatment . Using the Hamilton Rating Scale for Depression ( HAM-D ) sleep disturbance factor score , patients were categorized into low ( high ( ≥4 ) baseline insomnia subgroups . Changes in depression and insomnia were assessed . Safety assessment s included treatment-emergent adverse events ( AEs ) , reasons for discontinuation , and AEs leading to discontinuation . In addition , AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation . Depression improvement , assessed with the HAM-D-17 total score , was similar among treatments in all patients ( p = 0.365 ) and the high ( p = 0.853 ) and low insomnia ( p = 0.415 ) subgroups . Insomnia improvement , assessed with the HAM-D sleep disturbance factor score , was similar among treatments in all patients ( p = 0.868 ) and in the high ( p = 0.852 ) and low insomnia ( p = 0.982 ) subgroups . Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening , any worsening , worsening at endpoint , or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup . Treatments were well tolerated in most patients . No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups . These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine , sertraline , and paroxetine in major depressive disorder patients . Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia", "BACKGROUND Depression is an international public health problem . The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder . METHODS Thirty-six in patients and out patients with a diagnosis of major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 30 mg/day ) or fluoxetine ( 20 mg/day ) . Efficacy was assessed by HAM-D-17 . Information about adverse events was obtained by question ing of participants and /or their examination . Assessment s were performed at weeks 0 , 1 , 2 , 3 , 4 and 6 . RESULTS Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period . Both treatment groups were well matched at baseline with respect to demographic and disease characteristics . Both drugs showed a significant improvement over the 6 weeks of treatment ( P mean + /- SEM HAM-D scores of two groups at weeks 1 , 2 , 3 , 4 , and at the end point . There were no significant differences between two groups in terms of response to treatment ( > or = 50 % decrease from baseline in HAM-D-17 total score ) and remission ( HAM-D-17 score of adverse events was statistically significant . CONCLUSION In this study , mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder", "This r and omized , multicenter , double-blind study was design ed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets ( ODT ) with venlafaxine extended-release ( XR ) formulation in out patients with major depression . Both treatments were administered in a rapidly escalating dosing regimen . Target doses ( mirtazapine ODT , 45 mg OD ; venlafaxine XR , 225 mg OD ) were reached by day 6 of treatment . On the primary efficacy parameter [ the average of the change in HAM-D ( 17-item ) total score on days 5 , 8 , 11 , and 15 ] , mirtazapine ODT was significantly superior to venlafaxine XR ( P = 0.008 ) . In addition , calculating the HAM-D score without the sleep items result ed in significant reductions in favor of mirtazapine ODT on days 8 ( P = 0.006 ) and 11 ( P = 0.037 ) . The proportion of responders ( HAM-D decrease of ≥50 % from baseline ) was higher in the mirtazapine ODT group on all assessment days , being significant on days 8 ( P = 0.002 ) , 11 ( P = 0.004 ) , and 22 ( P = 0.027 ) . More patients in the mirtazapine ODT group achieved remission ( HAM-D total score of ≤7 ) up to day 29 , and the difference was statistically significant on day 15 ( P = 0.016 ) . Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 ( P = 0.019 ) , 11 ( P = 0.004 ) , and 15 ( P = 0.031 ) , and the CGI of severity on days 8 ( P = 0.014 ) and 11 ( P = 0.033 ) . Both treatments were well tolerated . These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy than venlafaxine XR in patients with major depressive disorder , and that this effect is independent of its sleep-improving properties", "Two hundred forty-one elderly depressed patients entered the 8-week , double-blind phase of this parallel-group , multicenter study ; 161 patients were r and omized to receive sertraline ( 50 - 200 mg/day ) and 80 were r and omized to receive amitriptyline ( 50 - 150 mg/day ) . Among evaluable patients , there were no statistically significant differences between treatments in any of the primary efficacy variables : change in total Hamilton Rating Scale for Depression ( HAM-D ) score ( 17 items ) , percentage change in HAM-D score , change in HAM-D Item 1 , change in Clinical Global Impressions ( CGI ) Severity score , change in the Depression Factor of the 56-item Hopkins Symptom Checklist , and the CGI Improvement score at the last visit . Similar results were obtained using data from all patients ( intention-to-treat analysis ) , except that amitriptyline was superior in HAM-D Total score ( p = .044 ) . The two drugs produced a similar degree of response : on the basis of the HAM-D criterion , 69.4 % of sertraline patients and 62.5 % of amitriptyline patients responded , and , on the basis of CGI criterion , 79.5 % of sertraline and 73.4 % of amitriptyline patients responded . Twenty-eight percent of the sertraline patients withdrew from the study because of a treatment-related side effect and 2.5 % ( 4 ) because of a laboratory abnormality . In comparison , 35 % of the amitriptyline patients withdrew because of treatment-related side effects . Sertraline was associated with a statistically lower frequency of somnolence , dry mouth , constipation , ataxia , and pain and a higher frequency of nausea , anorexia , diarrhea/loose stools , and insomnia ; thus , anticholinergic effects were less common and gastrointestinal effects were more common with sertraline than with amitriptyline . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied . The extent and implication s of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated , to the authors ' knowledge . METHOD The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry , the Archives of General Psychiatry , the Journal of Clinical Psychopharmacology , and the Journal of Clinical Psychiatry between 2001 and 2003 . RESULTS Among 397 clinical trials identified , 239 ( 60 % ) reported receiving funding from a pharmaceutical company or other interested party , and 187 studies ( 47 % ) included at least one author with a reported financial conflict of interest . Among the 162 r and omized , double-blind , placebo-controlled studies examined , those that reported conflict of interest were 4.9 times more likely to report positive results ; this association was significant only among the subset of pharmaceutical industry-funded studies . CONCLUSIONS Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo", "OBJECTIVE Few controlled studies have addressed the issue of which antidepressant medications should be recommended for out patients who have not responded to multiple treatment trials . This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant ( nortriptyline ) following two prospect i ve , consecutive , unsuccessful medication treatments for nonpsychotic major depressive disorder . METHOD Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks ( first step ) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone ( second step ) , adult out patients ( N=235 ) with nonpsychotic major depressive disorder were r and omly assigned to 14 weeks of treatment with mirtazapine ( up to 60 mg/day ) ( N=114 ) or nortriptyline ( up to 200 mg/day ) ( N=121 ) . The primary outcome , symptom remission , was defined a priori as a total exit score of Rating Scale for Depression . The 16-item Quick Inventory of Depressive Symptomatology-Self-Report ( QIDS-SR(16 ) ) , obtained at treatment visits , provided secondary outcomes of remission ( score response ( > /=50 % reduction in score from baseline ) . RESULTS For mirtazapine , remission rates were 12.3 % and 8.0 % per the Hamilton and QIDS-SR(16 ) scores , respectively . For nortriptyline , remission rates were 19.8 % and 12.4 % , respectively . QIDS-SR(16 ) response rates were 13.4 % for mirtazapine and 16.5 % for nortriptyline . Neither response nor remission rates statistically differed by treatment , nor did these two treatments differ in tolerability or adverse events . CONCLUSIONS Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials result ed in low remission rates ( < 20 % ) among patients with major depressive disorder", "& NA ; This study compared the efficacy and safety of the selective serotonin reuptake inhibitor sertraline with that of the tricyclic antidepressant clomipramine in patients with severe depression , as defined by a baseline 17‐item Hamilton Depression Rating Scale ( HAM‐D ) of at least 25 . The study included 166 out patients , r and omized to double‐blind treatment with sertraline ( 50‐200 mg ) or clomipramine ( 50‐150 mg ) for 8 weeks . The efficacy of both treatments was similar , 74 % of patients in the sertraline group and 71 % of clomipramine patients being classified as responders at the end‐point , as defined by a Clinical Global Impression‐Improvement ( CGI‐I ) score of 1 or 2 . Mean HAM‐D scores fell from 29.8 at baseline to 12.3 at endpoint in the sertraline group , and from 29.6‐12.7 in the clomipramine group . There were more withdrawals due to adverse events in the clomipramine group than in the sertraline group ( 17 % versus 12 % ) . Dry mouth , tremor , dizziness and constipation were all substantially more common in the clomipramine group , whereas diarrhoea / loose stools was more common in the sertraline group . Overall , sertraline was as effective as clomipramine in this group of severely depressed out patients , and showed better tolerability", "BACKGROUND There has been a paucity of well- design ed studies comparing selective serotonin reuptake inhibitor ( SSRI ) medications in the treatment of depression in the elderly . This multicenter study was design ed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly out patients . A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function . METHOD Two hundred thirty-six out patients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being r and omly assigned to 12 weeks of double-blind , parallel-group treatment with flexible daily doses of either sertraline ( range , 50 - 100 mg ) or fluoxetine ( range , 20 - 40 mg ) . Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings . Secondary outcome assessment s included clinician- and patient-rated measures of depression symptoms and factors , cognitive functioning , and quality of life , as well as plasma drug concentrations , which were correlated with clinical response . RESULTS Both drugs produced a similarly positive response on the primary efficacy measures , with 12-week responder rates of 73 % for sertraline and 71 % for fluoxetine . Sertraline-treated patients showed statistically greater cognitive improvement on several measures . Both drugs were safe and well tolerated . CONCLUSION Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly out patients . Differences in cognitive performance effects deserve further investigation", "ABSTRACT Objectives : To evaluate the efficacy and safety of trazodone prolonged-release compared with sertraline in the treatment of patients with major depression . Research design and methods : A total of 122 patients aged 19–64 years were enrolled in this multicenter , double-blind , double-dummy , r and omized , comparator-controlled study . Patients received 7 days of single-blind placebo treatment followed by 6 weeks of double-blind treatment with trazodone prolonged-release 150–450 mg/day ( n = 62 ) or sertraline 50–100 mg/day ( n = 60 ) . Outcome measures : Efficacy was evaluated by mean changes from baseline in the Hamilton Depression Rating scale ( HAM‐D ) , Montgomery Asberg Depression Rating Scale , Hamilton Anxiety Rating scale , and the Clinical Global Impression-Global Improvement/Severity scores ; and by the rates of patients responding to treatment and considered to be in remission . Time to onset of efficacy and safety were assessed . Results : Trazodone and sertraline were equally effective in reducing depressive symptoms and promoting remission , and had similar onset times . In the Intent-to-Treat population , there were no significant differences in favor of trazodone at study endpoint in all efficacy measures , while a statistically significant difference was detected in the Per- Protocol population on HAM‐D and in the percentage of responders . Analysis of HAM‐D factors ( anxiety/somatization , cognitive disturbance , retardation , and sleep disturbance ) indicated that sleep disturbances were significantly less evident for patients taking trazodone at study endpoint . Adverse drug reactions , mostly of mild intensity , were reported in 42 % of trazodone-treated patients ( mainly of the nervous system ) and 43 % of sertraline-treated patients ( mainly gastrointestinal ) . One event was considered to be serious : a patient treated with trazodone 450 mg/day showed moderate anxiety/tremor/insomnia and was hospitalized . Treatment was discontinued ; the patient made a full recovery . Conclusions : This study showed that after 6 weeks , trazodone and sertraline were not different in reducing symptoms of depression and in producing disease remission . Tolerability profiles reflected the differing pharmacological properties of these antidepressants . Trazodone may be a therapeutic option in the treatment of patients with major depression showing prevalent sleep disturbances", "The aim of this multicenter , r and omized , double-blind , 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features . Patients with a baseline score of ≥ 25 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to receive treatment with either mirtazapine ( N = 78 , 15–60 mg/day ) or venlafaxine ( N = 79 , 75–375 mg/day , twice a day ) in a rapid up-titration schedule . Efficacy was assessed with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , HAM-D-17 , and Clinical Global Impression scale , and quality of life was assessed with the Quality of Life , Enjoyment , and Satisfaction Question naire and Quality of Life in Depression Scale . Tolerability was assessed with the Utvalg for Kliniske Undersogelser ( UKU ) side effect scale and by reporting adverse events . Both drugs were effective in reducing overall symptoms of depression , showing substantial reductions in group mean MADRS scores ( −20.1 for mirtazapine and −17.5 for venlafaxine ) and HAM-D-17 scores ( −17.1 for mirtazapine and −14.6 for venlafaxine ) at the end of the treatment . Although not statistically significant , at all assessment times higher percentages of patients treated with mirtazapine were classified as responders ( ≥50 % reduction ) on the HAM-D ( at endpoint , 62 % vs. 52 % ) and MADRS ( at endpoint : 64 % vs. 58 % ) . Likewise were the percentages of remitters ( HAM-D score ≤7 ; MADRS score ≤12 ) also higher in the mirtazapine group . A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points ( p ≤ 0.03 ) . Both treatments were well tolerated . Although slightly more subjects treated with mirtazapine reported at least one adverse event , a statistically significantly higher percentage of patients treated with venlafaxine ( 15.3 % ) than mirtazapine ( 5.1 % ) dropped out because of adverse events ( p = 0.037 ) . Quality of life improved in both treatment groups . In this study , treatment with mirtazapine result ed in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events", "Hnyberg OJ , Maragakis B , Mullin J , Norum D , Stordall E , Ekdahl P , Ose E , Moksnes KM , Sennef C. A double‐blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients . Acta Psychiatr Sc and 1996 : 93 : 184–190 . © Munksgaard 1996", "An eight-week double-blind , multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression ( DSM-III-R ) . There were 108 out- patients , from nine Italian centres , entered into the study , of whom 88 were evaluable ( 48 sertraline , 40 fluoxetine ) . The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg . Both treatment groups showed a statistically significant improvement from baseline at one week , and this was maintained until the end of treatment for all of the following measures : Hamilton Rating Scales for Depression and Anxiety , the Montgomery Asberg Depression Rating Scale , Clinical Global Impressions Scale , Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Question naire . Although there was a numerical advantage for sertraline on several efficacy measures , there was no statistically significant difference found between the treatment groups . The incidence of adverse events was similar for both treatments ; 40.4 % for sertraline and 39.3 % for fluoxetine . However , adverse events were generally rated by patients as of lower severity in the sertraline group . In addition , for the fluoxetine group , there was a higher incidence of agitation , anxiety and insomnia than for sertraline . Sertraline was considered to be better tolerated than fluoxetine overall , since only 9.6 % of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6 % . By contrast , 13.5 % of sertraline-treated patients discontinued prematurely because of clinical improvement , compared with 10.7 % of fluoxetine-treated patients", " One hundred and sixty-three patients with major depression were r and omly assigned to treatment with mirtazapine or doxepin for 6 weeks in a double-blind clinical trial . Initially , patients received mirtazapine 20 mg/day or doxepin 75 mg/day ; dosages were then titrated up to a maximum of 60 mg/day and 300 mg/day , respectively . Both drugs produced considerable improvement in depressive symptoms with no statistically significant differences between the two patient groups . In the mirtazapine group only two patients prematurely terminated the study due to adverse drug experiences , as compared to six in the doxepin-treated group . Moreover , doxepin-treated patients complained more frequently of dry mouth and movement disorders . In conclusion , mirtazapine is an effective treatment for major depression and appears to offer advantages in tolerability over doxepin", "BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a \" positive \" study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions", "The efficacy and tolerability of moclobemide and sertraline were compared in a 13 week trial on 55 depressive patients . Patients were diagnosed according to DSM-III-R criteria using SCID ( Structured Clinical Interview for DSM-III-R ) . The study group was composed of 48 patients with major depression and 7 with minor depression . Patients were r and omized in two drug groups and raters were blind to the drugs patients used . HDRS and CGI were used to assess the change in depressive symptoms . Twenty seven patients received moclobemide and 28 patients received sertraline . The dose of moclobemide used was 300 - 600 mg/day and that of sertraline was 50 - 200 mg/day . At the end of 13 weeks mean drop in HDRS for the overall group was 14.78 and the response rate calculated as percentage of patients showing a 50 % drop in HDRS score was 77.8 . The response rate was 76.5 % for moclobemide and 78.5 % for sertraline . The difference was not significant . The side effects were assessed by using UKU Side Effects Rating Scale . The most three observed side effects were dry mouth , headache and insomnia", "OBJECTIVES The adrenal and rogen dehydroepi and rosterone-sulfate ( DHEA-S ) seems to be involved in the pathophysiology of depression , although its precise role in the etiology and remission of depression remains unclear . In the present study we intended to examine possible differential effects of venlafaxine and mirtazapine in a r and omised open trial with regard to DHEA-S serum concentrations in patients suffering from major depressive episode compared to healthy controls . METHODS We assessed DHEA-S concentrations both at baseline and after a 4-week treatment period in 70 depressed patients ( n=33 for venlafaxine and n=37 for mirtazapine ) and 33 matched healthy controls . RESULTS We describe the decrease of DHEA-S levels in depressive patients who remitted after treatment with both venlafaxine or mirtazapine . Patients without remission of depression did not show a significant decline in DHEA-S concentrations . CONCLUSIONS Our results suggest an effect of treatment outcome upon DHEA-S concentrations rather than a direct drug effect . The change of plasma DHEA-S levels as a marker of treatment-response of depression warrant further investigation", "reuptake inhibitors ( SSRIs ) during continuation therapy . This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression , quality of life , and personality outcomes . Out patients with unipolar major depression ( DSM-III-R ) were r and omly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine ( 20 - 40 mg ) or sertraline ( 50 - 150 mg ) . Assessment s included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression Scale , the Battelle Quality of Life Question naire , and the Structured Clinical Interview for DSM-III-R Personality Disorders screen question naire . One hundred seventy-six patients ( mean age , 43 years ; 64 % female ; baseline MADRS , 30.3 ) were treated with sertraline and 177 patients ( mean age , 42 years ; 71 % female ; MADRS , 30.7 ) with paroxetine . Antidepressant efficacy during continuation therapy was sustained , with only 2 % of patients receiving sertraline and 9 % of patients receiving paroxetine suffering a relapse . Continuation therapy result ed in a substantial conversion of responders during short-term treatment to full remission : remitter rates increased from 52 % to 80 % for sertraline and from 57 % to 74 % for paroxetine . The improvements in quality of life were related to a reduced depression score . SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality . A logistic regression analysis identified early response ( 25 % reduction in MADRS scores at week 2 ) as the most important predictor of treatment response , whereas high severity , chronicity , and poor baseline quality of life had no effect . Both treatments were well-tolerated , with sertraline having a somewhat lower side effect profile . Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy . Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology", "OBJECTIVE The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed in patients . METHOD Forty depressed in patients diagnosed according to DSM-IV-TR criteria were r and omly assigned to treatment with either reboxetine ( N = 20 ) or mirtazapine ( N = 20 ) . To control for retest effects in psychomotor measures , a group of 10 healthy controls was examined on the same time schedule . Participants were tested once before pharmacologic treatment and twice after initiation of treatment ( days 7 and 14 ) with computerized tests related to car-driving skills . Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem , measuring visual perception , reactivity , stress tolerance , concentration , and vigilance . In addition , patients went through various risk simulations on a static driving simulator . Data were analyzed with nonparametric statistics and repeated- measures analysis of variance . The study was conducted from June 2004 through June 2006 . RESULTS Before onset of treatment with antidepressants , about 65 % of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety . After 14 days of treatment with reboxetine or mirtazapine , patients improved in driving ability skills . Controlling for retest effects in psychomotor measures , data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity ( all p frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine ( all p partially remitted depressed in patients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives", "OBJECTIVE This study was design ed to evaluate the comparative efficacy and safety of sertraline and nortriptyline for the treatment of major depressive disorder in older adults . METHOD A double-blind , parallel group design was used to compare 210 out patients , 60 years of age and older , who met DSM-III-R criteria for major depressive episode and had a minimum Hamilton Depression Rating Scale score of 18 . The patients were r and omly assigned to 12 weeks of treatment with either sertraline ( 50 - 150 mg/day ) or nortriptyline ( 25 - 100 mg/day ) . RESULTS The safety profiles of the two treatments were similar except that nortriptyline treatment was associated with a significant increase in pulse rate , whereas sertraline was associated with a nonsignificant decrease . Efficacy of both drugs was similar for both treatments at all time points , with 71.6 % ( N=53 of 74 ) of the sertraline-treated patients and 61.4 % ( N=43 of 70 ) of the nortriptyline-treated patients achieving responder status by week 12 . Time to response was also similar , with more than 75 % of the improvement in scores on the Hamilton depression scale having occurred by week 6 . Secondary efficacy measures ( posttreatment measures of cognitive function , memory , and quality of life ) revealed a significant advantage for sertraline treatment . CONCLUSIONS Primary efficacy measures showed sertraline and nortriptyline to be similarly effective . With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group . The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment", "BACKGROUND A sustained-release formulation of bupropion ( bupropion SR ) , developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form , has not been evaluated in active comparator trials . This r and omized , double-blind , parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline . METHOD Out patients with moderate to severe major depressive disorder ( DSM-IV ) received bupropion SR ( 100 - 300 mg/day ) or sertraline ( 50 - 200 mg/day ) for 16 weeks . Psychiatric evaluations , including the Hamilton Rating Scale for Depression ( HAM-D ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Clinical Global Impressions scale for Severity of Illness ( CGI-S ) , and for Improvement ( CGI-I ) were completed , and adverse events were assessed in the clinic periodically throughout treatment . Patients ' orgasm function was also assessed . RESULTS Mean HAM-D , HAM-A , CGI-I , and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group ; no between-group differences were observed on any of the scales . Orgasm dysfunction was significantly ( p sertraline-treated patients compared with bupropion SR-treated patients . The adverse events of nausea , diarrhea , somnolence , and sweating were also experienced more frequently ( p sertraline-treated patients . No differences were noted between the two treatments for vital signs and weight . CONCLUSION This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression . Both compounds were relatively well tolerated , and orgasm dysfunction , nausea , diarrhea , somnolence , and sweating were reported more frequently in sertraline-treated patients", "BACKGROUND The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine . METHOD 275 out patients with a diagnosis of major depressive episode ( DSM-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 15 - 45 mg/day ) or paroxetine ( 20 - 40 mg/day ) . Efficacy was assessed by the HAM-D-17 , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scales ( Severity and Improvement ) , and analyses were performed on the intent-to-treat sample ( 127 mirtazapine-treated patients and 123 paroxetine-treated patients ) . RESULTS Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine . Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out . Both drugs were equally effective in reducing symptoms of depression . At week 1 , the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients ( 16.5 vs. 18.8 , p = .0032 ) . Similarly , significantly more mirtazapine-treated patients were HAM-D-17 responders ( > or = 50 % decrease from baseline ) at weeks 1 ( 23.2 % vs. 8.9 % , p = .002 ) and 4 ( 58.3 % vs. 44.5 % , p = .04 ) . Both treatments were equally effective in reducing anxiety . However , the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 ( -5.1 vs. -3.5 , p = .0435 ) . Tolerability of both treatments was good , with more nausea , vomiting , tremor , and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group . CONCLUSION Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated . A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression", "BACKGROUND Most studies report a poor response of psychotic depressed patients to treatment with a tricyclic antidepressant alone compared to combined treatment with an antipsychotic preparation and compared to non-psychotic depressed patients . However , the issue of optimal treatment of psychotic depressed patients has not been resolved as yet . Previously , we reported a significant difference in response to mirtazapine compared to imipramine in a r and omised , double-blind , fixed-blood-level study with in- patients with major depression . In the current study we focus on the treatment response to imipramine in a group of patients with psychotic depression and compare this to patients who manifest no psychotic features . Our aim in presenting these findings was to contribute to the discussion on the optimal treatment of psychotic depressed patients . METHODS Fifty-two patients with a unipolar major depression ( DSM-IIIR ) , comprising 15 patients with mood-congruent psychotic features and 37 patients with no psychotic features , were commenced on treatment with imipramine after a drug-free and placebo-washout period of 7 days . The dose of imipramine was adjusted for all patients to a predetermined blood level . The Hamilton ( HRSD ) and Montgomery-Asberg ( MADRS ) Depression Rating Scales were used to evaluate treatment response . RESULTS Of the 45 patients who completed the study , nine of the 13 psychotic patients ( 69.2 % ) and 14 of the 32 non-psychotic patients ( 43.8 % ) responded to treatment . The patients with psychotic features demonstrated a lower mean final HRSD score , together with a greater fall in MADRS score over time , compared to the non-psychotic group . Both these findings remained statistically significant after controlling for a number of possible confounding factors . CONCLUSIONS These results demonstrate that , in this group of patients with mood-congruent psychotic depression , imipramine used on its own together with strict control of serum drug levels produced a high treatment response rate of 70 % . CLINICAL IMPLICATION S If replicated , these findings suggest that imipramine with control of blood levels of medication may be a useful first-line treatment for depressed patients with mood-congruent psychotic features . LIMITATIONS Our sample size was modest . This fact may caution against generalisation of the results", "Abstract Introduction : Depression is a major global problem associated with large medical , sociological and economic burdens . Mirtazapine ( Remeron ® , Organon NV , The Netherl and s ) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression . However , this agent has not yet been tested in patients with severe depression alone . Objective : To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression ( ≥25 points on the first 17 items of the Hamilton Depression Rating Scale [ HDRS-17 ] ) . Methods : In this double-blind study , 297 severely depressed patients were r and omised to receive mirtazapine 15–60 mg/day ( n = 147 ) or fluoxetine 20–40 mg/day ( n = 152 ) for 8 weeks . 294 subjects were actually treated and 292 included in the intent-to-treat population . Symptom severity was measured by the HDRS-17 , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) rating scale . Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Question naire and the Quality of Life , Enjoyment and Satisfaction Question naire . Adverse events were recorded throughout the study . Results : No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point ; both treatments were associated with large ( ∼15 points ) decreases by study end . However , more mirtazapine-treated patients tended to exhibit a ≥50 % decrease in HDRS score ( significant at day 7 ; 9.0 % vs 0.7 % , p = 0.002 ) . Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores ( −10.9 vs −8.5 , p = 0.006 ) and the proportion of patients with ≥50 % decrease in MADRS score ( 21.4 % vs 10.9 % , p = 0.031 ) . On the CGI , the proportion of ‘ much/very much improved ’ patients tended to be greater with mirtazapine ( significant at day 7 ; 9.7 % vs 3.4 % , p = 0.032 ) . No significant between-group differences were observed for the majority of quality -of-life measures . However , mirtazapine produced significantly better improvements on ‘ sleeping assessment 1 ’ ( 14.9 ± 5.2 vs 13.7 ± 5.4 , p = 0.028 ) and ‘ sleeping assessment 2 ’ ( p = 0.013 ) than fluoxetine . Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7 kg compared with a mean decrease in weight of 0.4 ± 2.1 kg for fluoxetine-treated patients ( p Conclusions : Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression", "OBJECTIVE To compare the efficacy , safety and tolerability of reboxetine and sertraline in major depressive disorder ( MDD ) . METHOD The study subjects consisted of 41 patients who met the DSM-IV MDD diagnostic criteria . Patients were r and omly assigned to receive either reboxetine or sertraline . During the study the patients were assessed 6 times ( baseline visit = day 0 , visit 1=day 8 , visit 2=day 22 , visit 3=day 36 , visit 4=day 57 and visit 5=day 78 ) over 11 weeks . Antidepressant response was measured by the Hamilton Depression Rating Scale ( HDRS ) , Clinical Global Impressions-Severity of Illness ( CGI-SI ) and Global Impressions-Global Improvement ( CGI-GI ) . RESULTS Comparing the two groups in terms of response and remission ( HAM-D remission was evaluated as HAM-D dry mouth , sweating , palpitation , headache , hot flushing and sedation were more frequent in the reboxetine group . Only one patient , in the reboxetine group , dropped out due to a side effect ( constipation ) . CONCLUSION Higher rates of full remission achievement , which is the main target of MDD treatment , in the reboxetine group compared with the sertraline group may be due to the suppression of anxiety symptoms by the noradrenergic feature of the drug . In order to underst and the role of the noradrenergic system in treating MDD , larger patient sample s are needed . Both reboxetine and sertraline were well tolerated and effective in treating MDD", "Abstract Objective : To evaluate the efficacy of emotional support and counselling combined with placebo or antidepressants with single or dual mechanism of action in the treatment of depression in primary care . Design : R and omised double blind study . Setting : Several locations in Norway . Subjects : 372 patients with depression . Main outcome measures : Improvement ( clinical remission ) reported both by the patient ( Montgomery Åsberg depression rating scale ) and the physician ( clinical global improvement and impression scales ) . Results : Intention to treat analyses showed 47 % remission in patients r and omised to placebo compared with 61 % remission in patients r and omised to sertraline ( odds ratio 0.56 , 95 % confidence interval 0.33 to 0.96 ) and 54 % in patients r and omised to mianserin ( 0.75 , 0.44 to 1.27 ) . Women responded better than men ( 1.86 , 1.17 to 2.96 ) . Subgroup analyses showed that subjects with recurrent depression ( n=273 ) responded more frequently to sertraline than to placebo ( 0.43 , 0.23 to 0.82 ) than those having their first episode of depression ( 1.18 , 0.39 to 3.61 ) . Statistically significant interactions between type of drug treatment and history of depression were not shown by logistic regression . Conclusion : The combination of active drug and simple psychological treatment ( counselling , emotional support , and close follow up over a 24 week period ) was more effective than simple psychological treatment alone , in particular for those with recurrent depression . Overall , women may benefit more than men . If confirmed in future studies , the findings should lead to more differentiated treatment guidelines for depression in primary care", "BACKGROUND This study was design ed to compare the efficacy , safety , tolerability profiles , and effects on quality of life of the serotonin selective reuptake inhibitor antidepressant sertraline versus the nonselective tricyclic antidepressant amitriptyline and placebo in patients with major depression . METHOD Out patients with DSM-III-R major depression were r and omly assigned to double-blind treatment for 8 weeks with sertraline ( 50 - 200 mg daily ) , amitriptyline ( 50 - 150 mg daily ) , or matching placebo . Assessment s included the Hamilton Rating Scale for Depression , Montgomery-Asberg Depression Rating Scale , Clinical Global Impressions-Severity of Illness scale , Clinical Global Impressions-Improvement scale , Global Assessment Scale , Profile of Mood States , Beck Depression Inventory , Quality of Life Enjoyment and Satisfaction Question naire , and Health-Related Quality of Life battery . RESULTS All treatment groups demonstrated statistically significant improvement from baseline in depression ratings by Week 1 and thereafter . The antidepressant effects of amitriptyline and sertraline were significantly ( p placebo and did not differ significantly from each other . Sertraline was associated with significantly ( p subjective ( i.e. , patient-rated ) improvement in mood than amitriptyline or placebo . Both active drugs were associated with greater improvements than placebo on most quality of life measurements . On several items , sertraline , but not amitriptyline , was superior to placebo . There was a discernible effect of sertraline earlier than amitriptyline on most quality of life scales . Amitriptyline therapy was associated with significantly more treatment-related adverse events , and discontinuations due to treatment-related adverse events , in comparison to both sertraline and placebo therapy . CONCLUSION Sertraline and amitriptyline each were effective treatments for major depression as assessed by both physician- and patient-rated scales . These results show that sertraline therapy is better tolerated than amitriptyline therapy . Quality of life was also improved by effective antidepressant treatment , with sertraline showing a tendency to produce greater improvements on quality of life measures", "BACKGROUND Sexual dysfunction commonly occurs during antidepressant treatment . However , the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature . The objectives of this study were ( 1 ) to estimate the prevalence of sexual dysfunction among patients taking newer antidepressants ( bupropion immediate release [ IR ] , bupropion sustained release [ SR ] , citalopram , fluoxetine , mirtazapine , nefazodone , paroxetine , sertraline , venlafaxine , and venlafaxine extended release [ XR ] ) and ( 2 ) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction . METHOD This cross-sectional , observational study was conducted in 1101 U.S. primary care clinics . Adult out patients ( 4534 women and 1763 men ) receiving antidepressant monotherapy were enrolled . The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Question naire . RESULTS In the overall population , bupropion IR ( 22 % ) and SR ( 25 % ) and nefazodone ( 28 % ) were associated with the lowest risk for sexual dysfunction , whereas selective serotonin reuptake inhibitor ( SSRI ) antidepressants , mirtazapine , and venlafaxine XR were associated with higher rates ( 36%-43 % ) . In a prospect ively defined sub population unlikely to have predisposing factors for sexual dysfunction , the prevalence of sexual dysfunction ranged from 7 % to 30 % , with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR . Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction . CONCLUSION Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a vali date d rating scale . Overall , SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone . Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians , greater recognition and education are imperative when prescribing antidepressant treatment ", "The purpose of this double-blind , multicenter trial was to compare the efficacy and safety of sertraline ( 50–150 ing/day ) with those of citalopram ( 20–60 mg/day ) in patients with major depression in general practice during 24 weeks of treatment . The patients were assessed using the Montgomery-Åsberg Depression Rating Scale and the Clinical Global Impressions of severity and improvement scales . Observed and spontaneously reported adverse events were recorded and side-effects were assessed by means of the UKU Side-Effect Scale . Altogether 400 patients were r and omized into the study . A total of 308 patients completed the 24-week study in accordance with the protocol . A significant reduction in the total Montgomery-Åsberg Depression Rating Scale scores was observed in both treatment groups as early as 2 weeks , with no statistically significant differences between the drugs . In the intention to treat-lust observation carried forward analysis 76 % responded to treatment in the sertraline and 81 % in the citalopram group . The final mean doses were 82 mg/day ( 64 % higher than baseline ) in the sertraline group and 34 mg/day ( 70 % higher than baseline ) in the citalopram group . The response rate in completers in accordance with protocol was 90 % in the sertraline group and 93 % in the citalopram group . The side-effects were those usually seen , and both sertraline and citalopram were considered to be well tolerated . It was concluded that patients with major depression in general practice respond well to 24 weeks of treatment with sertraline or citalopram . With regard to efficacy , no statistically significant differences were found between the drugs", "INTRODUCTION : Reboxetine is the first available selective noradrenaline re-uptake inhibitor ( selective NRI ) . This paper gives an overview of its antidepressant efficacy and tolerability in eight r and omized double-blind , multicentre clinical trials . The clinical profile of reboxetine is also compared with that of the tricyclic antidepressants ( TCAs ) desipramine and imipramine and the selective serotonin re-uptake inhibitor ( SSRI ) fluoxetine . METHODS : Pooled data were analysed from seven short-term ( 4 - 8 weeks ) and one long-term ( up to 1 year ) trials comparing reboxetine with placebo , imipramine , desipramine or fluoxetine . The tolerability of reboxetine was evaluated in 2613 patients with major depression or dysthymia . Data from 1959 patients with major depressive disorder were included to assess drug efficacy . Efficacy was principally assessed using the Hamilton Depression Rating Scale ( HAM-D ) . RESULTS : Reboxetine was more effective than placebo in three of four short-term trials , and it was as effective as fluoxetine , imipramine and desipramine . In long-term treatment , reboxetine was more effective than placebo in preventing relapse ( S 50 % increase in HAM-D ) and recurrence ( HAM-D total score h 10 ) . In a subset of severely depressed patients , reboxetine was as effective as imipramine and significantly more effective than fluoxetine . Reboxetine was as effective as imipramine in the elderly , but better tolerated . The most common adverse events among the 1503 patients ( adults and elderly ) who received reboxetine were dry mouth ( 22 % ) , constipation ( 15 % ) , sweating ( 12 % ) and insomnia ( 11 % ) . Overall , reboxetine was well tolerated , as well as the SSRI fluoxetine and better than the TCAs imipramine and desipramine . CONCLUSIONS : Reboxetine is effective and well tolerated in the short and long-term treatment of depression . It is as well tolerated as fluoxetine and better than imipramine and desipramine . ( Int J Psych Clin Pract 2000 ; 4 : 201 - 208", "BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression", "AIMS Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder ( MDD ) . The aim of this r and omised , open-label , controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms . METHODS A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale ( HARS ) were r and omly assigned to 8 weeks of fixed dosing treatment with mirtazapine ( 15 - 30 mg/day ) and paroxetine ( 10 - 20 mg/day ) . Efficacy was primarily assessed with the HARS and with the 17-item Hamilton Depression Rating Scale ( HDRS ) at weeks 1 , 2 , 4 and 8 after treatment . Tolerability was assessed from adverse events . RESULTS The generalised estimating equations ( GEE ) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups . However , patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2 . Week-by-week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment ( week 1 ) and maintained through week 2 . There was no difference in the overall frequency of adverse events experienced between the two treatment groups . The most common adverse event in the mirtazapine group was somnolence ( n = 8) , whereas that in the paroxetine group was gastrointestinal discomfort ( n = 9 ) . CONCLUSIONS Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms . Mirtazapine was , however , more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment , suggesting that mirtazapine may have an earlier-onset action for the anxiety symptoms in MDD patients", "AIM To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression . METHOD 133 patients with a diagnosis of major depressive episode ( DSM-IV ) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were r and omly assigned to receive 6 weeks of treatment with either mirtazapine ( 15 - 45 mg/day ) or fluoxetine ( 20 - 40 mg/day ) . Efficacy was assessed using the HAM-D and Clinical Global Impressions scale , with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method . Safety analysis was based on the all-subjects-treated group . RESULTS Mean daily doses were 34.1 mg for mirtazapine ( N = 66 ) and 30.7 mg for fluoxetine ( N = 66 ) . Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out . Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period . At day 42 , the mean reductions in HAM-D total score ( compared with baseline ) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups , respectively ; however , the changes were not statistically significant . Both treatments were well tolerated , with more nausea and influenza-like symptoms observed for the fluoxetine group , and greater weight increase and somnolence for the mirtazapine analog . CONCLUSION Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms , and both were well tolerated by our population of depressed Chinese patients . In line with analogous Western reports , the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients ; however , slightly different side effect profiles were noted for the 2 drugs in our study", "BACKGROUND The purpose of this study was to compare the overall effectiveness of 2 treatment strategies for in patients with severe major depressive episode ( DSM-III-R ) : ( 1 ) mirtazapine ( phase 1 ) and subsequent lithium addition ( phase 2 ) or ( 2 ) imipramine ( phase 1 ) and subsequent lithium addition ( phase 2 ) . We previously reported the results of phase 1 . METHOD In phase 1 , patients were r and omly assigned to treatment with either mirtazapine or imipramine , and doses were adjusted to obtain predefined blood drug levels . Nonresponders had lithium added to the double-blind mirtazapine or imipramine medication . The dose was adjusted to obtain a blood lithium level of 0.5 - 1.0 mmol/L. Treatment effects were evaluated weekly by the Montgomery-Asberg Depression Rating Scale for up to 2 weeks on this blood lithium level . RESULTS Data for 100 patients were available for comparison of the 2 treatment strategies . 80 patients received no comedication . By the end of phase 2 , 24 ( 48 % ) of 50 had responded to mirtazapine and 32 ( 64 % ) of 50 had responded to imipramine ( intent-to-treat analysis ) . A survival analysis of the total patient group intent-to-treat showed a significant difference in favor of the treatment strategy with imipramine and subsequent lithium addition . CONCLUSION Efficacy of imipramine and subsequent lithium addition for nonresponders is superior to the same treatment strategy with mirtazapine . This applies to the patient sample studied , which consisted of 100 severely depressed in patients , 29 of whom were psychotically depressed . More serious side effects of imipramine , however , led to discontinuation of imipramine in 5 patients . No serious side effects were observed during the phase of lithium addition to either imipramine or mirtazapine . We , therefore , prefer to start treatment with imipramine and test for fixed blood drug levels , and , if necessary , add lithium . In the case of prohibitive side effects , patients are switched to a modern antidepressant such as mirtazapine , and , if necessary , lithium is added to this antidepressant", "Efficacy and acceptability of tianeptine were investigated in a multicenter , r and omized , double blind , and sertraline-controlled study . As a total , 212 in- or out patients with DSM IV major depression single episode , recurrent and bipolar depression , were treated for 42 days either with tianeptine ( 37.5 mg ) or with sertraline ( 50 mg ) . At inclusion , sociodemographic , physical and psychological parameters showed no significant intergroup differences . MADRS responders ( 50 % reduction of baseline score ) were 66 % and 67 % with tianeptine and sertraline , respectively . No statistical interdrug differences were observed either in the number of withdrawals or in the efficacy and acceptability parameters", "The acute treatment efficacy , tolerability , and effects on health-related quality of life of sertraline ( 50 - 200 mg/day ) versus imipramine ( 75 - 225 mg/day ) were compared in out patients with non-melancholic depression . The study employed an open-label , parallel-group design . One hundred and sixteen patients were r and omized to receive sertraline and 123 to receive imipramine for 8 weeks . In the intent-to-treat ( ITT ) , last-observation-carried-forward ( LOCF ) analysis , sertraline produced statistically significantly greater improvements in depressive ( 21-item Hamilton Depression Rating Scale [ HAM-D(21 ) ] scores of 24.9 and 24.4 were reduced to 10.3 and 13.1 at endpoint , P anxiety symptoms ( Hamilton Anxiety Rating Scale [ HAM-A ] scores of 21.8 and 21.9 were reduced to 9.5 and 13.9 , P remission rates ( 51.3 % versus 38.0 % at endpoint , P=.041 ) from week 4 onwards compared with imipramine . The proportion of patients who were ' very much improved ' or ' much improved ' ( Clinical Global Impressions Scale of Improvement [ CGI-I ] score of 1 or 2 ) was significantly higher at endpoint in the sertraline group ( 76.1 % ) than in the imipramine group ( 62.8 % ) ( P=.028 ) . At week 8 , patients in both treatment groups showed clear improvements in quality of life , although nonstatistically significant differences were evident in the quality of life of sertraline- versus imipramine-treated patients . Sertraline was significantly superior in tolerability with less discontinuations due to adverse events ( 10.3 % ) compared with the imipramine group ( 24.4 % ) ( P=.004 ) . It was concluded that sertraline is more effective than imipramine in the acute treatment of depressive and anxiety symptoms in patients with non-melancholic depression", "Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability", "OBJECTIVE The authors sought to identify genetic markers for antidepressant medication intolerance . Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 ( CYP2D6 ) has been postulated to underlie antidepressant intolerance ( pharmacokinetic effect ) . However , variation in genes encoding serotonin receptors could also explain antidepressant side effects ( pharmacodynamic effect ) . METHOD An 8-week , double-blind , r and omized pharmacogenetic study compared the widely prescribed antidepressants paroxetine ( a selective serotonin reuptake inhibitor [ SSRI ] ) and mirtazapine ( not an SSRI ) in 246 elderly patients with major depression . Genotypes were determined for the 102 T/C single nucleotide polymorphism ( SNP ) in the serotonin 2A ( 5-HT(2A ) ) locus ( HTR2A ) , previously associated with psychotropic medication treatment outcome . Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene . Clinical outcomes included treatment discontinuations , adverse events , medication compliance , and change in mood . RESULTS Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype . There was a significant linear relationship between the number of C alleles and the probability of discontinuation . Side effect severity in paroxetine-treated patients with the C/C genotype was also greater . In contrast , HTR2A 102 T/C genotype had no effect on mirtazapine side effects . CYP2D6 genotype did not predict treatment outcome for either medication . CONCLUSIONS Pharmacodynamic differences among patients due to variant 5-HT(2A ) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance . Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome", "This study compared the efficacy and tolerability of 150 mg/day imipramine and 50 mg/day sertraline for the treatment of a major depressive episode ( DSM-IV ) in older adults ( N = 55 ) in an 8-week , r and omized , double-blind , controlled clinical trial . Intention-to-treat analysis ( last observation carried forwards ) showed a reduction of 50 % or more on the baseline scores of the Montgomery-Asberg Rating Scale ( MADRS ) in 60.7 % and 55.6 % of patients receiving imipramine and sertraline , respectively ( p = .698 ) . Full remission of symptoms ( MADRS Side effects were more frequent among patients treated with imipramine ( 86.7 % ) than among patients treated with sertraline ( 42.1 % ) ( p = .008 ) . Dropout rates were high in both groups ( 46.4 % and 29.6 % respectively , p = .200 ) . These results indicate that imipramine and sertraline are equally effective for the treatment of major depression in later life , although adverse reactions are more frequent among subjects treated with imipramine than with sertraline", "BACKGROUND The prevalence of major depressive disorder in patients with acute coronary syndromes ( ACSs ) is high and associated with worse cardiovascular outcomes and higher health care costs . Sertraline is the only treatment for major depressive disorder studied in a placebo-controlled trial of patients with ACS and found to be safe and effective . The cost implication s of providing antidepressant treatment in this population have not yet been examined . The objective was to evaluate from a payer perspective the potential reduction in costs and psychiatric and cardiovascular events and procedures following sertraline versus placebo treatment of major depressive disorder in patients hospitalized for ACS . METHOD Data were analyzed from a r and omized , double-blind , placebo-controlled 24-week trial ( Sertraline Antidepressant Heart Attack R and omized Trial ) of sertraline treatment for major depressive disorder in patients hospitalized for ACS . Main outcome measures included frequency and costs ( derived from Medicare diagnosis-related group fee schedules ) of psychiatric and cardiovascular events occurring during the treatment period . RESULTS There was a trend toward significantly fewer psychiatric or cardiovascular hospitalizations in the sertraline compared with the placebo group ( 55/186 vs. 76/183 ; p = .054 ) . The mean per patient cost associated with psychiatric and medical events over the course of treatment was 2733 US dollars for sertraline and 3326 US dollars for placebo , but the difference was not statistically significant ( p = .32 ) . After including the costs of the sertra-line ( 360 US dollars over 24 weeks ) , there was no increase in treatment costs for sertraline compared with placebo . CONCLUSION Sertraline treatment of major depressive disorder following hospitalization for a recent myocardial infa rct ion or unstable angina appears to be a cost-effective strategy", "This multinational , r and omized , double-blind study was specifically design ed to prospect ively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice . A total of 345 patients with major depressive episode ( DSM-IV ) received mirtazapine ( 30–45 mg/d ) or sertraline ( 50–150 mg/d ) for 8 weeks . Mirtazapine was administered in the newly developed fast dissolving , orally disintegrating tablet formulation . Assessment s were performed at baseline and on days 4 , 7 , 10 , 14 , 28 , 42 , and 56 . The primary efficacy variable ( mean absolute change from baseline in the Hamilton Depression Rating Scale [ HAMD ] total score [ 17 items ] ) showed that mirtazapine was significantly ( P sertraline at all assessment s during the first 2 weeks of the study . After this time , HAMD total scores were similar in both groups . These findings were supported by analysis of the HAMD response rate ( ie , ≥50 % reduction in HAMD total score from baseline ) , HAMD remission rate ( HAMD total score of ≤7 ) , and the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . Both treatments were well tolerated . In addition , mirtazapine had a greater effect than sertraline on sexual functioning . In conclusion , this first prospect i ve onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect than sertraline . The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient", "OBJECTIVE To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed in patients and out patients . METHOD Patients with a major depressive episode ( DSM-III-R ) , a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) , and > or=2 on HAM-D Item 1 ( depressed mood ) were r and omly assigned to a 6-week treatment with either mirtazapine ( N=66 , 15 - 60 mg/day ) or fluoxetine ( N=67 , 20 - 40 mg/day ) . The upper limit of the mirtazapine dose range was above the dose range approved in the United States ( 15 - 45 mg/day ) . Efficacy was evaluated by the HAM-D , Clinical Global Impressions , the Visual Analogue Mood Rating Scale ( VAMRS ) , and the Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method . RESULTS Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group . The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period , reaching statistical significance at days 21 and 28 . At assessment s from day 21 and onward , the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points , the magnitude of difference usually seen between an efficacious antidepressant drug and placebo . Mean dosages at weeks 1 - 4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine ; the respective dosages at weeks 5 - 6 were 56.3 mg and 35.8 mg . Similar numbers of patients dropped out due to adverse events ; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group . CONCLUSION We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy", "Spectral analysis of fluctuations in heart rate ( HR ) and blood pressure ( BP ) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine ( IMI ) or mirtazapine ( MIR ) . In a double-blind r and omized study , 10 patients received treatment with IMI and 10 patients received treatment with MIR . Cardiovascular parameters were studied before and after 4 weeks of treatment : HR and BP ( Finapres ) were recorded continuously during supine rest ( SR ) and orthostatic challenge ( OC ; 60-degrees head-up tilting ) . During SR and OC , power spectra were calculated for HR and systolic BP . Spectral density was assessed for three frequency b and s : low ( 0.02 - 0.06 Hz ) , mid ( 0.07 - 0.14 Hz ) , and high ( 0.15 - 0.50 Hz ) . Before treatment , the depressed patients ( N = 20 ) differed from age-matched controls ( N = 20 ) only in their response to OC : the depressed patients showed more suppression of HR variability ( both mid- and high-frequency b and fluctuations ) , indicating stronger vagal inhibition , and a reduced increase of BP variability ( mid-frequency b and fluctuations ) , indicating reduced sympathetic activation . After 4 weeks of treatment , patients treated with either antidepressant drug showed significant changes of HR ( increase ) and HR variability ( decrease ) during SR and OC ; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR . The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI ( strong ) and MIR ( weak ) , result ing in cardiac vagal inhibition . Whereas MIR had no effect on BP or BP variability , IMI specifically reduced mid-frequency b and fluctuations of BP as the result of a suppression of central sympathetic activity . Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients : spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved , specifically during OC . The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs . In fact , some of the components of the cardiovascular autonomic dysfunction were further aggravated , depending on the pharmacologic profile of the drug under investigation", "OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression", "A double-blind , placebo- and amitriptyline-controlled comparison study was performed to evaluate the antidepressant efficacy of sertraline , a specific serotonin uptake inhibitor . Patients with DSM-III-defined major depression r and omly received either sertraline ( N = 149 ) , amitriptyline ( N = 149 ) , or placebo ( N = 150 ) once daily for the 8-week study period . The mean final daily medication dose for the all- patients group was 145 mg and 104 mg for the sertraline- and amitriptyline-treatment groups , respectively . As measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions Scale , both the sertraline and amitriptyline treatment groups showed a significantly greater improvement from baseline ( p less than or equal to .001 ) than the placebo group . The sertraline group had a higher proportion of gastrointestinal complaints and male sexual dysfunction than either the amitriptyline or the placebo group . The amitriptyline group showed a higher proportion of anticholinergic and sedative side effects and dizziness compared with patients who received either sertraline or placebo", "Rationale Amplitude , habituation and prepulse inhibition ( PPI ) of the acoustic startle response ( ASR ) in rodents and humans are sensitive to psychotropic drugs . Studies with rodents suggest that an increase or decrease in serotonin level in the brain alters several modalities of the ASR . So far , little is known about serotonergic and noradrenergic startle modulation in humans . Objective This study was design ed to investigate the effects of the selective serotonin uptake inhibitor sertraline versus the selective noradrenalin uptake inhibitor reboxetine on magnitude , habituation and PPI of ASR in patients with major depression . Methods We studied ASR in 23 patients with the diagnosis of major depression according to DSM-IV who were r and omly treated either with sertraline or with reboxetine . Initially , ASR assessment was carried out when patients were drug-free for at least 2 weeks and again after 14 days of treatment . Results The habituation of ASR was strongly attenuated by sertraline and not significantly altered by reboxetine . None of the substances altered the startle reactivity . In addition , PPI was not altered by sertraline , but reboxetine tended to decrease PPI . The startle reactivity at baseline was correlated with improvement of depressive symptoms at the end of the study . Conclusion These results provide the first evidence for different effects of noradrenergic and serotonergic antidepressants on the startle response in depressed patients", "& NA ; The aim of this study was to examine response and remission rates in out patients treated with sertraline or fluoxetine who were suffering from two depression subtypes : anxious‐depression and severe depression . Data were pooled from five double‐blind studies comparing fluoxetine versus sertraline for the treatment of DSM‐III‐R or IV major depression . Clinical outcome was assessed using the Hamilton Depression Rating Scale ( HAM‐D ) and the Clinical Global Impression‐Improvement scale ( CGI‐I ) . One thous and and eighty‐eight patients were r and omized , with 654 ( 60 % ) meeting criteria for anxious depression and 212 ( 19 % ) meeting criteria for high severity depression . For the total sample , treatment response was similar for both sertraline and fluoxetine . In the high severity subgroup , the mean ( ±SD ) HAM‐D score at week 12 was 8.9±5.7 for sertraline and 10.8±6.9 for fluoxetine ( P=0.07 ) , and the mean ( ±SD ) CGI‐I score was 1.5±0.7 for sertraline and 2.0±1.1 for fluoxetine ( P=0.005 ) . CGI‐I responder rates were 88 % versus 71 % ( P=0.03 ) in the high severity subgroup , and 84 % versus 79 % ( P=0.16 ) in the anxious‐depression subgroup . Overall , sertraline and fluoxetine showed comparable antidepressant efficacy , although sertraline may offer an advantage in those patients with severe depression", "BACKGROUND Sleep complaints are common in patients with major depressive disorder ( MDD ) . Both MDD and antidepressant drugs characteristically alter objective sleep measures . This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia . METHOD Patients ( N = 19 ) received initial baseline polysomnography evaluations over 2 consecutive nights . Subjects were r and omly assigned to either fluoxetine ( 20 - 40 mg/day ) or mirtazapine ( 15 - 45 mg/day ) treatment for an 8-week , double-blind , double-dummy treatment trial . Single-night polysomnograms were conducted at weeks 1 , 2 , and 8 , with depression ratings assessed at baseline and weeks 1 , 2 , 3 , 4 , 6 , and 8 . Statistical analysis was performed by repeated- measures analysis of variance followed by Dunnet 's post hoc analyses . RESULTS Patients receiving mirtazapine ( N = 8) had significant improvement in objective sleep physiology measures at 8 weeks . Improvements in sleep latency , sleep efficiency , and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment . No significant changes in sleep continuity measures were observed in the fluoxetine group ( N = 11 ) . Both groups improved clinical ly in mood and subjective sleep measures from baseline , with no differences between groups . CONCLUSION These data demonstrate the differential effects of mirtazapine and fluoxetine , with significant improvement in favor of mirtazapine , on objective sleep parameters in MDD patients with insomnia", "There is clinical and biological evidence suggesting that patients with anger attacks , sudden spells of anger accompanied by intense autonomic activation , may represent a distinct psychopathological subgroup of patients with depressive disorders . We compared the prevalence of anger attacks in 168 out patients with atypical depression or primary dysthymia with 38 normal subjects and tested the effect of treatment on anger attacks in a double-blind , placebo-controlled trial of sertraline versus imipramine . Patients were r and omly assigned to sertraline ( n = 56 ) , imipramine ( n = 52 ) , or placebo ( n = 60 ) and were administered the Anger Attacks Question naire before and after treatment . Depressed out patients were significantly more likely to report anger attacks than controls . Anger attacks ceased in 53 percent of the patients receiving sertraline , 57 percent of those receiving imipramine , and 37 percent of those in the placebo group . Our findings support previous studies indicating that anger attacks are more prevalent among depressed out patients than normals . Our results also suggest that sertraline and imipramine may be more effective than placebo in reducing the number of anger attacks following treatment although the differences were not statistically significant . Larger studies are needed to confirm our findings", "Depression is associated with considerable morbidity and mortality . As depressive disorders carry a high risk of relapse , treatment strategies include the use of a 6-month continuation period after resolution of the acute episode . Tolerability is of major importance when determining compliance and outcome during long-term therapy . Due to the superior tolerability profile of the selective serotonin reuptake inhibitors ( SSRIs ) over the older tricyclic antidepressants ( TCAs ) , the former may be more suitable for extended therapy . Comparative studies have not shown differences between the SSRIs in terms of efficacy , but side-effect profiles may vary . A multicenter , double-blind , comparative study of sertraline and fluoxetine was carried out in out patients fulfilling DSM-III-R criteria for major depressive disorder . Patients were r and omised to receive sertraline ( 50 - 150 mg , n = 118 ) or fluoxetine ( 20 - 60 mg , n = 120 ) for 24 weeks . Assessment s for depression ( HAM-D , HAD , CGI-I , CGI-S ) , anxiety ( Covi ) , sleep ( Leeds Sleep Evaluation scale ) and quality of life ( SIP ) were made at study entry and at weeks 2 , 4 , 8 , 12 , 18 and 24 . All adverse events were recorded to allow evaluation of tolerability . In total , 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group . Side effects were responsible for the premature treatment withdrawal of seven ( 6 % ) sertraline patients and 12 ( 10 % ) fluoxetine patients . Two-hundred and thirty-four patients were included in an ITT analysis up to last visit ( 116 sertraline , 118 fluoxetine ) . At study endpoint , both treatments produced a significant improvement over baseline on all efficacy variables ( P changes in depression , anxiety , and quality of life was larger with sertraline than fluoxetine , none of the between-group differences reached statistical significance . However , significant differences in favour of sertraline were observed for individual HAM-D items including item 4 ( insomnia onset ) ( P = 0.04 ) , item 9 ( agitation ) ( P = 0.02 ) , and item 13 ( general somatic symptoms ) ( P = 0.008 ) . In addition , sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest , emotional behaviour and ambulation . Both sertraline and fluoxetine were well tolerated with no significant differences between treatments", "Sexual dysfunction , a frequently reported side effect of many antidepressants , may result in patient dissatisfaction and noncompliance with treatment regimens . This paper describes the results of the first placebo-controlled comparison of the efficacy , safety , and effects on sexual functioning of sustained-release bupropion ( bupropion SR ) and the selective serotonin reuptake inhibitor sertraline . This r and omized , double-masked , double-dummy , parallel-group , multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression . Patients were treated with bupropion SR 150 to 400 mg/d , sertraline 50 to 200 mg/d , or placebo for up to 8 weeks . Patients ' depression and sexual functioning were assessed at weekly or biweekly clinic visits ; safety was assessed by regular monitoring of adverse events , vital signs , and body weight . Treatment groups were similar at baseline in terms of age , sex , and race , and most patients had a diagnosis of moderate uncomplicated depression . Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures ; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points . Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo ( P Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group ( 30 % to 40 % ) . Nausea ( 31 % ) , diarrhea ( 26 % ) , insomnia ( 18 % ) , and somnolence ( 17 % ) occurred in significantly more patients in the sertraline group than in the bupropion SR group ( 18 % , 7 % , 13 % , and 3 % , respectively ) and the placebo group ( 10 % , 11 % , 4 % , and 6 % , respectively ) . Dry mouth occurred more frequently with bupropion SR ( 19 % ) than with sertraline ( 14 % ) or placebo ( 12 % ) , although the differences were not significant . Changes in vital signs were similar in all groups . Similar ( small , but not statistically significant ) decreases in mean body weight were seen in both the bupropion SR ( -1.06 kg ) and sertraline ( -0.79 kg ) groups , whereas the placebo group experienced a minor increase ( 0.21 kg ) . Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression , sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo . Therefore , bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients", "We aim ed to compare the antidepressant and anxiolytic effects , tolerability and effects on quality of life of mirtazapine and citalopram in a r and omized , double-blind , multicentre , 8-week study . Patients with a Major Depressive Episode ( DSM-IV ) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were r and omized to 8 weeks treatment with either mirtazapine ( n = 137 , 15 - 60 mg/day ) or citalopram ( n = 133 , 20 - 60 mg/day ) . Efficacy was evaluated by the MADRS , Hamilton Anxiety Scale ( HAM-A ) , Clinical Global Impression scales ( CGI ) , the Leeds Sleep Evaluation Question naire ( LSEQ ) and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method . Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit . The magnitude of reduction from baseline in group mean MADRS scores was large in both groups , reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group . Both treatments also result ed in a substantial improvement in anxiety symptoms , sleep disturbances and quality of life , and high percentage of responders . However , at day 14 , statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS , HAM-A and CGI-Severity of illness and Quality of life scores . A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinical ly relevant superiority between two proven antidepressants . Mirtazapine treatment was also related to faster improvement of sleep , quality of sleep and improved alertness following awakening , as shown by statistically significant differences on the self-rating LSEQ at various time points . There were no differences between two treatment groups on self-rating QLSEQ . Both drugs were well tolerated , with a low number of patients in either group prematurely terminating the study due to adverse events ( mirtazapine : 3.6 % , citalopram , 3.0 % ) . Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group . There were no clinical ly relevant changes in laboratory parameters and vital sign variables with either treatment , except for clinical ly relevant increase in body weight , occurring more frequently in mirtazapine patients . In this study , mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety , and well tolerated . However , mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS , HAM-A and CGI Severity of illness and Quality of life scales . This finding , consistently present at all major efficacy variables , suggests potentially faster onset of efficacy of mirtazapine over citalopram", "OBJECTIVE To compare the change in severity of depressive symptoms and occurrence of side effects in primary care patients treated with St John 's wort ( SJW ) and sertraline . DESIGN Double-blind , r and omized 12-week trial . SETTING Community-based offices of 12 family physicians practising in greater Montreal , Que . PARTICIPANTS Eighty-seven men and women with major depression and an initial score of > or = 16 on the Hamilton Rating Scale for Depression ( Ham-D ) . INTERVENTIONS Patients were r and omized to treatment with either sertraline ( 50 to 100 mg/d ) or SJW ( 900 to 1800 mg/d ) in a double-blind fashion . Assessment of depression was done at entry and at 2 , 4 , 8 , and 12 weeks using the Ham-D , the Beck Depression Inventory ( BDI ) , and a question naire asking about compliance and side effects . MAIN OUTCOME MEASURES Changes from baseline in Ham-D and BDI scores and self-reported side effects . RESULTS There were no important differences in changes in mean Ham-D and BDI scores ( using intention-to-treat analysis ) , with and without adjustment for baseline demographic characteristics , between the two groups at 12 weeks . Significantly more side effects were reported in the sertraline group than in the SJW group at 2 and 4 weeks ' follow up . CONCLUSION The more benign side effects of SJW make it a good first choice for this patient population", "To compare the efficacy and tolerability of antidepressants switch with extended-release venlafaxine ( venlafaxine-XR ) , mirtazapine , and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials . One hundred fifty adult patients with treatment-resistant depression according to their medical records and /or response to current treatments were r and omly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d ( n = 50 ) , mirtazapine 45 mg/d ( n = 55 ) , or paroxetine 20 mg/d ( n = 45 ) for 8 weeks . The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) . Secondary outcomes included the remission rate defined by the Self-Rating Depression Scale of 50 or lower and the response rate defined by a 50 % reduction or greater on the HRSD-17 total score , and the improvement of patients ' general health functions . The completion rates were 82 % for venlafaxine-XR , 81.8 % for mirtazapine , and 82.2 % for paroxetine . Only one patient in paroxetine arm discontinued the study owing to an adverse event . The remission rates based on the HRSD-17 were 42.0 % for venlafaxine-XR , 36.4 % for mirtazapine , and 46.7 % for paroxetine . There were no statistical significance s between treatment arms in remission rates . Similarly , there were also no significant differences between groups in secondary outcome measure . Venlafaxine-XR , mirtazapine , and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments . Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients", "Lowering the concentrations of free cortisol in depressed patients may be an important prerequisite to prevent glucocorticoid-related sequelae of depression . We tested the hypothesis that the hypothalamus-pituitary-adrenal ( HPA ) system-dampening effects of venlafaxine and mirtazapine differ . We compared the course of morning ( 08.00h ) and afternoon saliva cortisol ( 16.00h ) in 42 mirtazapine- and 45 venlafaxine-treated depressed patients during a 1-week wash-out and a 4-week treatment period in a r and omised open trial . Mirtazapine lowered afternoon cortisol from week 1 to 4 . In contrast , during the course of the entire treatment period , venlafaxine did not attenuate saliva cortisol concentrations . Treatment effects of mirtazapine on cortisol concentrations did not differ in remitters and non-remitters to treatment . High baseline cortisol concentrations , on the other h and , were related to an unfavourable course during venlafaxine treatment and patients remitting during venlafaxine treatment had significantly lower afternoon cortisol concentrations in saliva , when compared to non-remitting patients . Thus , mirtazapine and venlafaxine show different effects on HPA system activity as measured by saliva cortisol . This may be of relevance with regard to physical sequelae of depression", "Patients ( n = 150 ) were r and omized to a 6-week , double-blind study to evaluate the relative efficacy and safety of mirtazapine , amitriptyline , and placebo in the treatment of major depressive disorder symptoms . Average daily modal doses were mirtazapine , 18 mg ; amitriptyline , 111 mg ; and placebo , 4.6 capsules . Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression ( HAM-D ) score reductions ( weekly visits 1 , 2 , 4 , and endpoint ) compared to placebo . These findings were supported by the Montgomery-Asberg Depression Rating Scale ( MADRS ) ; the Zung Self-rating Depression Scale ( SDS ) ; and the Clinical Global Impressions ( CGI ) scales . Somnolence and weight gain were the only adverse clinical experiences ( ACEs ) reported substantially more often by mirtazapine-treated patients than by those in the placebo group . However , more amitriptyline-treated patients reported decreased visual accommodation , dry mouth , dyspepsia , constipation , tachycardia , hypertension , hypotension , discoordination , dizziness , and tremor than mirtazapine- or placebo-treated patients . Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients , and superior to amitriptyline in respect to anticholinergic and cardiovascular effects", "This double-blind study compared initial combination therapy against monotherapy using two antidepressant drugs with complementary mechanisms of action on the serotonin ( 5-HT ) and norepinephrine ( NE ) systems . Sixty one adult patients with a DSM-IV diagnosis of unipolar depression were r and omized to receive mirtazapine ( 30 mg/day ) , paroxetine ( 20 mg/day ) , or the combination of both drugs for 6 weeks . Response at week 4 was defined as a 30 % reduction in the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and at week 6 as a 50 % reduction in the MADRS . Remission was defined as a reduction in the MADRS score to 10 points or less . After 4 weeks , non-responders in the monotherapy groups had their medication dose increased by 50 % . After 6 weeks , non-responders on monotherapy had the second trial drug added to their current regimen . Non-responders on combination therapy had the dosage of both drugs increased by 50 % . There was a significantly greater decrease in MADRS scores in the combination group compared to the monotherapy groups at days 28 , 35 and 42 , with a 10 point difference separating the combination from the monotherapies at day 42 . Remission rates at week 6 were 19 % on mirtazapine , 26 % on paroxetine , and 43 % on the combination . Fifteen patients in the mirtazapine arm and 10 in the paroxetine arm who did not respond had the other drug added to their current regimen , and 5 on the combination had an increase in dose of both drugs secondary to non-response . Of these 30 patients , approximately 50 % went on to achieve remission in the subsequent 2 weeks . These results indicate that the combined use of two antidepressants was well tolerated and produced a greater improvement than monotherapy", "In this double-blind study in primary care patients , the efficacy and safety of sertraline , an antidepressant which is a selective inhibitor of serotonin re-uptake , was compared with clomipramine . Patients with DSM-III-defined major depression and with significant anxiety r and omly received 50 - 150 mg of either sertraline ( N=51 ) or clomipramine ( N=55 ) once daily for 6 weeks . The mean final daily dose was 63.5 mg sertraline and 60.6 mg clomipramine . Seventy five percent of sertraline-treated and 79 % of clomipramine-treated patients were maintained on the lowest dose of 50 mg once daily . The mean scores of all the rating scales ( HAM-D , HAM-A , HAD , CGI ) showed similar efficacy between the treatments in reducing the symptoms of depression and anxiety . Clomipramine was less well tolerated than sertraline with a greater overall incidence of side effects , or significantly greater incidence of anticholinergic side effects and significantly more patient withdrawals due to side effects ; 18 % in the clomipramine group compared with 4 % in the sertraline group . The results indicate that sertraline is an effective agent to use in primary care patients with depression and associated symptoms of anxiety and is better tolerated than the tricyclic comparator clomipramine", "BACKGROUND In nursing home residents and other frail elderly patients , old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications . The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents . METHOD The study was a 10-week r and omized , double-blind , controlled trial of venlafaxine ( doses up to 150 mg/day ) versus sertraline ( doses up to 100 mg/day ) among 52 elderly nursing home residents with a DSM-IV depressive disorder and , at most , moderate dementia . The primary measure of outcome was the Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were monitored and recorded systematic ally during the trial . RESULTS Twelve subjects were discontinued due to serious adverse events ( SAE ) , 5 were discontinued due to other significant side effects , and 2 withdrew consent . Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events ( log rank statistic = 5.28 , p = .022 ) , for serious adverse events or side effects ( log rank statistic = 8.08 , p = .005 ) , or for serious adverse events , side effects , or withdrawal of consent ( log rank statistic = 10.04 , p = .002 ) . Mean ( SD ) HAM-D scores at baseline were 20.2 ( 3.4 ) for sertraline and 20.3 ( 3.7 ) for venlafaxine ; intent-to-treat endpoint HAM-D scores were 12.2 ( 5.1 ) and 15.7 ( 6.2 ) ( F = 3.45 ; p = .069 ) . There were no differences in categorical responses for the intent-to-treat sample or completers . CONCLUSION In this frail elderly population , venlafaxine was less well tolerated and , possibly , less safe than sertraline without evidence for an increase in efficacy . This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly", "BACKGROUND Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine . METHOD A r and omized , single-blind , parallel-group study of 10 weeks ' duration comparing the efficacy of sertraline , 50 mg/day ; sertraline , 100 mg/day ; and fluoxetine , 20 mg/day , was conducted in 44 psychiatric out patients with DSM-IV unipolar major depressive disorder . Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission . Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Global Impressions-Improvement scale ( CGI-I ) , with scores of positive treatment response were noted , with 0 % for sertraline , 50 mg ; 46 % for sertraline , 100 mg ; and 31 % for fluoxetine , 20 mg ( p = .023 ) . At 6 weeks , positive treatment response rates were 21 % , 43 % , and 31 % for subjects taking 50 mg of sertraline , those taking 100 mg of sertraline , and those taking 20 mg of fluoxetine , respectively , with treatment groups no longer differing significantly from each other . In subjects for whom antidepressant dose was doubled at week 6 , response rates at week 10 ( 4 weeks on increased dose ) were 40 % for sertraline , 100 mg ; 43 % for sertraline , 200 mg ; and 55 % for fluoxetine , 40 mg . CONCLUSION Subjects taking sertraline , 100 mg , and fluoxetine , 20 mg , demonstrated an earlier treatment response compared with subjects taking sertraline , 50 mg . For patients without a positive response at 6 weeks , an increased antidepressant dose result ed in remission for a substantial proportion of patients when assessed 4 weeks later", "Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression . After a previous report of a marked difference in the response to mirtazapine compared to imipramine , we report here an analysis of different symptom clusters . One hundred seven consecutive in- patients with major depression ( Diagnostic and Statistical Manual III-R , DSM-III-R ) and a Hamilton Rating Scale for Depression ( HRS-D ) score of 18 points or more were r and omly assigned to double-blind treatment . Two and four weeks after predefined blood levels had been obtained , the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine , the latter being in excess of the 15 - 45 mg/day range currently advised . Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients ( 79 % ) who were not receiving any co-medication . Imipramine was more effective against the clusters related to core symptoms of depression : \" depression and guilt \" , \" retardation \" , and \" melancholia \" , respectively . Mirtazapine showed a biphasic response with regard to the clusters \" sleep \" and \" anxiety/agitation \" , respectively , which consisted of a marked response after two weeks of predefined blood level , but with a waning of this effect at four weeks . Imipramine produced a more gradual response on these clusters , which was more pronounced at four weeks than with mirtazapine . Two aspects of the present study could be related to this finding : blood level control result ed in optimal treatment with imipramine but not mirtazapine , and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication . These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in- patients", "The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials", "Genetic variation at the FKBP5 locus has been reported to affect clinical outcomes in patients treated with antidepressant medications in several studies . However , other reports have not confirmed this association . FKBP5 may regulate the sensitivity of the hypothalamic – pituitary – adrenal axis . We tested two FKBP5 single nucleotide polymorphisms ( rs1360780 and rs3800373 ) in a sample of 246 geriatric patients treated for 8 weeks in a double‐blind r and omized comparison trial of paroxetine and mirtazapine . These two polymorphisms had previously been reported to predict efficacy in depressed patients treated with selective serotonin reuptake inhibitors such as paroxetine , and those treated with mirtazapine , an agent with both serotonergic and noradrenergic actions . However , we found no significant associations between these FKBP5 genetic variants and clinical outcomes . Neither mean Hamilton Depression Rating Scale scores nor time to remission or response were predicted by FKBP5 genetic variation . These results suggest that FKBP5 is unlikely to play a major role in determining antidepressant treatment outcomes in geriatric patients . © 2009 Wiley‐Liss ," ]	411860d0-06ff-11f0-808a-c43d1ab1c353
Background : Bariatric surgery is currently the most efficacious treatment for obesity and its associated metabolic co-morbidities , such as diabetes . The metabolic improvements occur through both weight-dependent and weight-independent mechanisms . Bile acids ( BAs ) have emerged as key signalling molecules that have a central role in modulating many of the physiological effects seen after bariatric surgery . This systematic review assesses the evidence from both human and animal studies for the role of BAs in reducing the metabolic complications of obesity following bariatric surgery . Methods : We conducted a systematic search of Medline and Embase data bases to identify all articles investigating the role of BAs in mediating the metabolic changes observed following bariatric surgery in both animal and human studies . Boolean logic was used with relevant search terms , including the following MeSH terms : ‘ bile acids and salts ’ , ‘ bariatric surgery ’ , ‘ metabolic surgery ’ , ‘ gastrointestinal tract/surgery ’ and ‘ obesity/surgery ’ . Results : Following data base search es ( n=1197 ) , inclusion from bibliography search es ( n=2 ) and de-duplication ( n=197 ) , 1002 search results were returned . Of these , 132 articles were selected for full-text review , of which 38 articles were deemed relevant and included in the review . The findings support the effects of BAs on satiety , lipid and cholesterol metabolism , incretins and glucose homoeostasis , energy metabolism , gut microbiota and endoplasmic reticulum stress following bariatric surgery . Many of these metabolic effects are modulated through the BA receptors FXR and TGR5 . We also explore a possible link between BAs and carcinogenesis following bariatric surgery . Conclusions : Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms . BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities	[ "Gastric bypass leads to the remission of type 2 diabetes independently of weight loss . Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation . We prospect ively studied 12 patients undergoing gastric bypass and six patients undergoing gastric b and ing over a 6-wk period . Plasma fibroblast growth factor (FGF)19 , stimulated by bile acid absorption in the terminal ileum , and plasma bile acids were measured . In canine and rodent models , we investigated changes in the gut hormone response after altered bile flow . FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric b and ing . In the canine model , both food and bile , on their own , stimulated satiety gut hormone responses . However , when combined , the response was doubled . In rats , drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response , reduced food intake , and lower body weight . In conclusion , after gastric bypass , bile flow is altered , leading to increased plasma bile acids , FGF19 , incretin . and satiety gut hormone concentrations . Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes", "CONTEXT Obstructive sleep apnea ( OSA ) is strongly related to obesity . Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA . OBJECTIVE To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 60 obese patients ( body mass index : > 35 and These patients had been prescribed continuous positive airway pressure ( CPAP ) therapy to manage OSA and were identified via accredited community sleep clinics . The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical research ers in Melbourne , Australia . Patients with obesity hypoventilation syndrome , previous bariatric surgery , contraindications to bariatric surgery , or significant cardiopulmonary , neurological , vascular , gastrointestinal , or neoplastic disease were excluded . INTERVENTIONS Patients were r and omized to a conventional weight loss program that included regular consultations with a dietitian and physician , and the use of very low-calorie diets as necessary ( n = 30 ) or to bariatric surgery ( laparoscopic adjustable gastric b and ing ; n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to r and omization . Secondary outcomes were changes in weight , CPAP adherence , and functional status . RESULTS Patients lost a mean of 5.1 kg ( 95 % CI , 0.8 to 9.3 kg ) in the conventional weight loss program compared with 27.8 kg ( 95 % CI , 20.9 to 34.7 kg ) in the bariatric surgery group ( P AHI decreased by 14.0 events/hour ( 95 % CI , 3.3 to 24.6 events/hour ) in the conventional weight loss group and by 25.5 events/hour ( 95 % CI , 14.2 to 36.7 events/hour ) in the bariatric surgery group . The between-group difference was -11.5 events/hour ( 95 % CI , -28.3 to 5.3 events/hour ; P = .18 ) . CPAP adherence did not differ between the groups . The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score ( mean , 9.3 [ 95 % CI , 0.5 to 18.0 ] ; P = .04 ) . CONCLUSION Among a group of obese patients with OSA , the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss . TRIAL REGISTRATION anzctr.org Identifier : 12605000161628", "Background : The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery . Methods : We prospect ively investigated the effects of the bilio-intestinal bypass ( BI-bypass ) with a wide cholecysto-jejunal anastomosis and of adjustable gastric b and ing ( AGB ) on blood lipid concentrations in obese patients . To clarify the mechanism of the hypocholesterolemic effect of the BI-bypass , daily fecal sterol excretion was measured by gas-liquid chromatography ( GLC ) . Results : At 1 year after BI-bypass compared to baseline , the hypercholesterolemic ( n=18 ) and the normocholesterolemic ( n=19 ) patients significantly reduced total ( −38 % and −27 % , respectively ) , LDL ( −47 % and −24 % , respectively ) and HDL ( −11 % and −13 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −25 % and −13 % , respectively ) . At 1 year after AGB , the total / HDL cholesterol ratio was significantly decreased ( −11 % ) compared to baseline in hypercholesterolemic ( n=12 ) but not in normocholesterolemic ( n=6 ) patients , while total and LDL cholesterol were not affected in both groups . At 3 years after BI-bypass compared to baseline , the hypercholesterolemic ( n=9 ) and the normocholesterolemic ( n=11 ) patients significantly reduced total ( −43 % and −28 % , respectively ) and LDL ( −53 % and −29 % , respectively ) cholesterol and total / HDL cholesterol ratio ( −38 % and −21 % , respectively ) . The BI-bypass induced a significant ( P in mean fecal cholesterol output . Conclusions : The BI-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output . BI-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia", "Objective Our objective was to investigate the role of bile acids in hepatic steatosis reduction after vertical sleeve gastrectomy ( VSG ) . Design and Methods High fat diet ( HFD ) induced obese C57Bl/6 mice were r and omized to : VSG , Sham operation ( Sham ) , Sham operation with pair feeding to VSG ( Sham-PF ) , or non-surgical controls ( Naïve ) . All mice were on HFD until sacrifice . Mice were observed post-surgery and data for body weight , body composition , metabolic parameters , serum bile acid level and composition were collected . Further hepatic gene expression by RNAseq and RT-PCR analysis was assessed . Results VSG and Sham-PF mice lost equal weight post-surgery while VSG mice had the lowest hepatic triglyceride content at sacrifice . The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss . Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid . These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes . Conclusion VSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone . VSG surgery increases serum bile acids that correlate with weight lost post-surgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis", "The physiological role of glucagon-like peptide-1 7 - 36 amide ( GLP-1 7 - 36 ) in man was investigated . GLP-1 7 - 36-like immunoreactivity was found in the human bowel ; its circulating level rose after oral glucose and after a test breakfast . When it was infused into seven volunteers at a rate to mimic its postpr and ial plasma concentration in the fasting state , plasma insulin levels rose significantly and glucose and glucagon concentrations fell . During an intravenous glucose load , it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations , compared with a control saline infusion , even inducing postinfusion reactive hypoglycaemia . By comparison , infusion of glucose-dependent insulinotropic peptide ( GIP ) to physiological levels was less effective in stimulating insulin release . These observations suggest that GLP-1 7 - 36 is a physiological incretin and that it is more powerful than GIP . The observation of greatly increased postpr and ial plasma GLP-1 7 - 36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder", "OBJECTIVE Increased delivery of bile acid salts ( BA ) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery . To further eluci date a potential role of BA in the secretion of GLP-1 and PYY , we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospect i ve , r and omized 1-year trial . DESIGN AND METHODS Patients received a st and ard test meal and blood was collected before and after eating , prior to , and 1 week , 3 months , and 12 months after surgery . RESULTS Pre-surgery , basal BA concentrations were significantly lower in bariatric patients than in healthy controls . One year post-surgery , bariatric patients expressed variably increased BA concentrations ( gastric bypass patients ∼2 fold increase , P ≤ 0.05 ) . However , whereas in both patient groups , marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery , changes in plasma BA followed a different pattern : basal and postpr and ial plasma BA concentrations increased much slower , more progressively with significant increases only 1-year post-surgery . CONCLUSIONS Based on these findings , BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients ", "Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome . Changes in intestinal and hepatic physiology after ileal interposition ( transposition ) surgery ( IIS ) are not well understood . Our aim was to eluci date the adaptation of the interposed ileum , which we hypothesized , would lead to early bile acid reabsorption in the interposed ileum , thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments . Rats with diet-induced obesity were r and omized to IIS , with 10 cm of ileum repositioned distal to the duodenum , or sham surgery . A subgroup of sham rats was pair-fed to IIS rats . Physiological parameters were measured until 6 wk postsurgery . IIS rats ate less and lost more weight for the first 2 wk postsurgery . At study completion , body weights were not different , but IIS rats had reversed components of the metabolic syndrome . The interposed ileal segment adapted to a more jejunum-like villi length , mucosal surface area , and GATA4/ILBP mRNA . The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi . IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum , suggesting an early and efficient reabsorption of primary bile acids . IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss . There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR , SHP , or NTCP expression . IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling . There is early reabsorption of primary bile acids despite selective \" jejunization \" of the interposed ileal segment . Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery ", "Abstract Objective . Exogenous bile acid ( BA ) administration is associated with beneficial metabolic effects very similar to those seen after Roux-en-Y gastric bypass ( RYGB ) surgery . Re-routing of bile into a biliopancreatic limb with simultaneous exclusion of food occurs after RYGB , with subsequent increased fasting plasma BAs . The study assessed fasting and post-pr and ial plasma BA response before and 15 months after RYGB . Material and methods . The prospect i ve study recruited 63 obese individuals ( 43 females ) , aged 43 ( 36–56 ) [ median ( IQR ) ] years . Blood sample s were collected before and every 30 min for 120 min after a st and ard 400 kcal meal . Fasting and post-pr and ial plasma BAs , glucagons like peptide-1 ( GLP-1 ) , –tyrosine ( PYY ) , fasting C-reactive protein ( CRP ) , glucose and insulin were measured and homeostasis model assessment -insulin resistance ( HOMA-IR ) was calculated . Results . Following RYGB , body mass index , CRP , fasting glucose and HOMA-IR decreased ; 43.7 ( 39.3–49.2 ) kg/m2 to 29.2 ( 25.1–35.0 ) kg/m2 , 7.9 ( 4.1–11.9 ) mg/L to 0.4 ( 0.2–1.0 ) mg/L , 5.5 ( 5.0–6.0 ) mmol/L to 4.6 ( 4.3–4.9 ) mmol/L and 5.9 ( 3.5–9.2 ) to 1.7 ( 1.1–2.2 ) , respectively , all P 0.001 . Fasting total BAs , GLP-1 and PYY increased after RYGB ; 1.69 ( 0.70–2.56 ) µmol/L to 2.43 ( 1.23–3.82 ) µmol/L ( P = 0.02 ) , 6.8 ( 1.5–15.3 ) pmol/L to 17.1 ( 12.6–23.9 ) pmol/L ( P post-pr and ial total BAs , total glycine-conjugated BAs , GLP-1 and PYY were greater after RYGB ; 486 ( 312–732 ) µmol/L/min versus 1012 ( 684–1921 ) µmol/L/min , 315 ( 221–466 ) µmol/L/min versus 686 ( 424–877 ) µmol/L/min , 3679 ( 3162–4537 ) pmol/L/min versus 5347 ( 4727–5781 ) pmol/L/min and 1887 ( 1423–2092 ) pmol/L/min versus 3296 ( 2534–3834 ) pmol/L/min , respectively , all P in post-pr and ial plasma BA response due to larger amounts of glycine-conjugated BAs . This suggests up regulation of BA production and conjugation after RYGB", "Male Hartley guinea pigs were r and omly allocated to one of four treatments , 10 guinea pigs per group , for 12 weeks . The control diet contained no ASBT inhibitor ( ASBTi ) or simvastatin . Low ASBTi ( LowASBTi ) and high ASBTi ( HighASBTi ) were monotherapies containing 0.03 g/100 g and 0.1 g/100 g of the ASBTi SC-435 . Combination therapy ( COMBO ) was a combination therapy consisting of 0.03 g/100 g ASBTi and 0.05 g/100 g simvastatin . Based on food consumption , guinea pigs received 17.2 and 47.8 mg/kg per day ASBTi in the ASBTi groups or 13.7 mg/kg per day ASBTi and 21.4 mg/kg per day simvastatin in the COMBO group . The amount of cholesterol in each diet was 0.25 g/100 g. LDL cholesterol was 40 and 70 % lower with the HighASBTi and COMBO treatments compared to controls . Plasma triglycerides ( TG ) were 70 % lower with COMBO therapy while HDL cholesterol was 43 - 47 % higher with all treatments . Hepatic free cholesterol was reduced 60 - 80 % with all treatments . Cholesterol content in the aortic arch was reduced by 25 and 42 % in the HighASBTi and COMBO groups . Fecal bile acids were increased by 2.5- and 4-fold with HighASBTi and COMBO treatments . These data suggest that the interruption in the enterohepatic circulation of bile acids by ASBTi and statin co-administration therapy cause a significant reduction in plasma cholesterol concentrations and attenuate the progression of atherosclerosis in guinea pigs", "AIMS The aim of this study was to evaluate the effect of laparoscopic Roux-en-Y gastric bypass ( RYGB ) surgery compared with usual care with and without Exenatide therapy in obese people with type 2 diabetes mellitus ( T2DM ) and hypertension . METHODS 108 obese T2DM with hypertension were enrolled and r and omly allocated to usual care ( group A ) , usual care plus Exenatide ( group B ) , and RYGB surgery ( group C ) . Demographic characteristics , metabolic parameters and cardiac structure/function along with inflammatory cytokines were measured and compared before and after 12 months . RESULTS At 12 months , diabetes remission had occurred in no patients in groups A and B versus 90 % in group C , and there was a significant decrease in requirement of antihypertensive drugs in group C compared with groups A and B ( P ( body mass index , hemoglobin A1c , homeostasis model assessment of insulin resistance , lipids ) , inflammation index ( high sensitivity C-reactive protein , tumor necrosis factor-α , high molecular weight adiponectin ) and cardiac structure ( left ventricular mass index ) were significantly improved in groups B and C , but patients in group C had the greatest degree of improvement ( P CONCLUSION RYGB surgery improves a number of parameters including cardiovascular function in obese hypertensive people with T2DM . This is likely to be due to , at least in part , an improvement in the abnormal metabolic panel and to reduced inflammation", "BACKGROUND : The physiological relevance of duodenal bile acids in the control of cholecystokinin release and pancreatic enzyme secretion is still unknown . AIMS : To provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid composition of the person under investigation . For maximal reduction of endogenous bile output the CCK-A receptor antagonist loxiglumide was infused intravenously . SUBJECTS AND METHODS : Seven healthy volunteers were studied on four different days by a duodenal marker perfusion technique . The individual bile acid composition in duodenal juice and test meal stimulated bile acid output was assessed on day 1 . Bile acids were perfused at an amount of 30 or 100 % as determined on day 1 in combination with the test meal in the presence or absence of loxiglumide . Pancreatic enzymes , bilirubin , and bile acid output were determined in duodenal juice . Plasma cholecystokinin ( CCK ) and plasma pancreatic polypeptide ( PP ) were measured radioimmunologically . RESULTS : Bile acid perfusion did not significantly alter stimulated pancreatic enzyme , bilirubin or bile acid output or plasma CCK . Loxiglumide did not alter basal CCK release but increased test meal stimulated CCK output fourfold ( p bile acids to the test meal at a dose resembling 30 % of bile acid output as determined on day 1 prevented this increase . Plasma PP concentration remained unchanged by bile acids and were mostly undetectable during loxiglumide infusion . CONCLUSIONS : The CCK producing cell is under constant suppression by intraduodenal bile acids which can not be further enhanced by a physiological bile acid mixture . However , removal of duodenal bile acids by inhibition of gall bladder contraction unmasks this suppression leading to a dramatic increase in plasma CCK levels . As little as one third of postpr and ially released bile acids completely reverse this effect . Bile acids are the most important luminal regulator of CCK release in humans", "Objective : To evaluate the physiologic importance of the satiety gut hormones . Background : Controversy surrounds the physiologic role of gut hormones in the control of appetite . Bariatric surgery remains the most effective treatment option for obesity , and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass . Methods : We correlated peptide YY ( PYY ) and glucagon-like peptide 1 ( GLP-1 ) changes within the first week after gastric bypass with changes in appetite . We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass . Finally , we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake . Results : Postpr and ial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass ( P Changes in appetite are evident within days after gastric bypass surgery ( P appetite continues . However , in patients with poor weight loss after gastric bypass associated with increased appetite , the postpr and ial PYY and GLP-1 responses are attenuated compared with patients with good weight loss ( P return of appetite and increased food intake ( P appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations , and appetite returns when the release of gut hormones is inhibited . The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implication s for the treatment of obesity", "BACKGROUND Studies in humans and other animals have shown that Roux-en-Y gastric bypass ( RYGB ) leads to increased energy expenditure ( EE ) . We analyzed several components of EE , such as the respiratory quotient ( RQ ) , resting metabolic rate ( RMR ) , and diet-induced thermogenesis ( DIT ) among patients before and after RYGB . METHODS In this prospect i ve clinical study , RMR , DIT , and RQ were measured by indirect calorimetry ( IC ) in the same patients before and 12 months after RYGB ( the preoperative and postoperative time points , respectively ) . Postpr and ial RQ and DIT were measured after patients consumed a st and ard ~270 kcal meal ( 62 % carbohydrates , 12 % proteins , and 26 % lipids ) . RESULTS The population studied consisted of 13 patients ( mean age 40.8 ± 6.7 years , 85 % female).At the postoperative ( postop ) time point , patients showed higher weight-adjusted RMR compared with the preoperative ( preop ) time point ( P ) . The absolute and weight-adjusted metabolic rates 20 minutes after the meal were increased postoperatively ( P increase in RQ was significantly higher in the postop than in the preop time point . CONCLUSION The observed patients showed increased EE , DIT , and RQ after RYGB surgery . These data may serve as important physiologic factors contributing to the loss and maintenance of weight after RYGB", "OBJECTIVE To prospect ively evaluate the effect of different types of bariatric surgery on lipid profile . METHODS Total cholesterol ( TC ) , High-Density-Lipoprotein cholesterol ( HDLc ) , Low-Density-Lipoprotein cholesterol ( LDLc ) and triglycerides ( TG ) levels were evaluated before surgery and at 3 different post-operative time-points ( 3 , 6 and 12 months ) in consecutive obese subjects undergoing mini-gastric bypass ( MGB ) or sleeve gastrectomy ( SG ) . RESULTS At baseline , 74 MGB and 86 SG subjects were comparable for lipid profile and prevalence of hypercholesterolemia/hypertriglyceridemia . During the post-operative follow-up , both MGB and SG subjects showed significant changes in lipid profile . However , at 3 months , MGB patients showed higher changes in TC ( β = 0.179 , p = 0.022 ) and TG ( β = 0.265 , p = 0.001 ) than those undergoing SG . At 6-month post-operative follow-up , these differences were confirmed only for TC . After a 12-month follow-up , MGB and SG were entirely comparable for changes in lipid profile with the exception of HDLc , whose changes were higher in SG group ( β = 0.130 , p = 0.039 ) . Overall , the probability to normalize lipid profile during the 12-month follow-up was similar in MGB and in SG patients ( OR:1.24 , 95%CI:0.41 - 3.76 , p = 0.689 ) . CONCLUSION Despites some differences at 3 - 6 post-operative months , during a 12-month follow-up , SG and MGB showed a similar efficacy in the improvement of lipid profile of obese patients", "BACKGROUND & AIMS The 7α-dehydroxylation of primary bile acids ( BAs ) , chenodeoxycholic ( CDCA ) and cholic acid ( CA ) into the secondary BAs , lithocholic ( LCA ) and deoxycholic acid ( DCA ) , is a key function of the gut microbiota . We aim ed at study ing the linkage between fecal BAs and gut microbiota in cirrhosis since this could help underst and cirrhosis progression . METHODS Fecal microbiota were analyzed by culture-independent multitagged-pyrosequencing , fecal BAs using HPLC and serum BAs using LC-MS in controls , early ( Child A ) and advanced cirrhotics ( Child B/C ) . A subgroup of early cirrhotics underwent BA and microbiota analysis before/after eight weeks of rifaximin . RESULTS Cross-sectional : 47 cirrhotics ( 24 advanced ) and 14 controls were included . In feces , advanced cirrhotics had the lowest total , secondary , secondary / primary BA ratios , and the highest primary BAs compared to early cirrhotics and controls . Secondary fecal BAs were detectable in all controls but in a significantly lower proportion of cirrhotics ( p Serum primary BAs were higher in advanced cirrhotics compared to the rest . Cirrhotics , compared to controls , had a higher Enterobacteriaceae ( potentially pathogenic ) but lower Lachonospiraceae , Ruminococcaceae and Blautia ( 7α-dehydroxylating bacteria ) abundance . CDCA was positively correlated with Enterobacteriaceae ( r=0.57 , p post-rifaximin , six early cirrhotics had reduction in Veillonellaceae and in secondary / primary BA ratios . CONCLUSIONS Cirrhosis , especially advanced disease , is associated with a decreased conversion of primary to secondary fecal BAs , which is linked to abundance of key gut microbiome taxa", "UNLABELLED The nuclear bile acid receptor , farnesoid X receptor ( FXR ) , is an important transcriptional regulator of liver metabolism . Despite recent advances in underst and ing its functions , how FXR regulates genomic targets and whether the transcriptional regulation by FXR is altered in obesity remain largely unknown . Here , we analyzed hepatic genome-wide binding sites of FXR in healthy and dietary obese mice by chromatin immunoprecipitation sequencing ( ChIP-seq ) analysis . A total of 15,263 and 5,272 FXR binding sites were identified in livers of healthy and obese mice , respectively , after a short 1-hour treatment with the synthetic FXR agonist , GW4064 . Of these sites , 7,440 and 2,344 were detected uniquely in healthy and obese mice . FXR-binding sites were localized mostly in intergenic and intron regions at an inverted repeat 1 motif in both groups , but also clustered within 1 kilobase of transcription start sites . FXR-binding sites were detected near previously unknown target genes with novel functions , including diverse cellular signaling pathways , apoptosis , autophagy , hypoxia , inflammation , RNA processing , metabolism of amino acids , and transcriptional regulators . Further analyses of r and omly selected genes from both healthy and obese mice suggested that more FXR-binding sites are likely functionally inactive in obesity . Surprisingly , occupancies of FXR , retinoid X receptor alpha , RNA polymerase II , and epigenetic gene activation and repression histone marks , and messenger RNA levels of genes examined , suggested that direct gene repression by agonist-activated FXR is common . CONCLUSION Comparison of genomic FXR-binding sites in healthy and obese mice suggested that FXR transcriptional signaling is altered in dietary obese mice , which may underlie aberrant metabolism and liver function in obesity", "BACKGROUND In short-term r and omized trials ( duration , 1 to 2 years ) , bariatric surgery has been associated with improvement in type 2 diabetes mellitus . METHODS We assessed outcomes 3 years after the r and omization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy . The primary end point was a glycated hemoglobin level of 6.0 % or less . RESULTS The mean ( ±SD ) age of the patients at baseline was 48±8 years , 68 % were women , the mean baseline glycated hemoglobin level was 9.3±1.5 % , and the mean baseline body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 36.0±3.5 . A total of 91 % of the patients completed 36 months of follow-up . At 3 years , the criterion for the primary end point was met by 5 % of the patients in the medical-therapy group , as compared with 38 % of those in the gastric-bypass group ( P The use of glucose-lowering medications , including insulin , was lower in the surgical groups than in the medical-therapy group . Patients in the surgical groups had greater mean percentage reductions in weight from baseline , with reductions of 24.5±9.1 % in the gastric-bypass group and 21.1±8.9 % in the sleeve-gastrectomy group , as compared with a reduction of 4.2±8.3 % in the medical-therapy group ( P for both comparisons ) . Quality -of-life measures were significantly better in the two surgical groups than in the medical-therapy group . There were no major late surgical complications . CONCLUSIONS Among obese patients with uncontrolled type 2 diabetes , 3 years of intensive medical therapy plus bariatric surgery result ed in glycemic control in significantly more patients than did medical therapy alone . Analyses of secondary end points , including body weight , use of glucose-lowering medications , and quality of life , also showed favorable results at 3 years in the surgical groups , as compared with the group receiving medical therapy alone . ( Funded by Ethicon and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 . )", "BACKGROUND Long‐term results from r and omized , controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited . METHODS We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body‐mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) of 27 to 43 were r and omly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux‐en‐Y gastric bypass or sleeve gastrectomy . The primary outcome was a glycated hemoglobin level of 6.0 % or less with or without the use of diabetes medications . RESULTS Of the 150 patients who underwent r and omization , 1 patient died during the 5‐year follow‐up period ; 134 of the remaining 149 patients ( 90 % ) completed 5 years of follow‐up . At baseline , the mean ( ±SD ) age of the 134 patients was 49±8 years , 66 % were women , the mean glycated hemoglobin level was 9.2±1.5 % , and the mean BMI was 37±3.5 . At 5 years , the criterion for the primary end point was met by 2 of 38 patients ( 5 % ) who received medical therapy alone , as compared with 14 of 49 patients ( 29 % ) who underwent gastric bypass ( unadjusted P=0.01 , adjusted P=0.03 , P=0.08 in the intention‐to‐treat analysis ) and 11 of 47 patients ( 23 % ) who underwent sleeve gastrectomy ( unadjusted P=0.03 , adjusted P=0.07 , P=0.17 in the intention‐to‐treat analysis ) . Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone ( 2.1 % vs. 0.3 % , P=0.003 ) . At 5 years , changes from baseline observed in the gastric‐bypass and sleeve‐gastrectomy groups were superior to the changes seen in the medical‐therapy group with respect to body weight ( ‐23 % , ‐19 % , and ‐5 % in the gastric‐bypass , sleeve‐gastrectomy , and medical‐therapy groups , respectively ) , triglyceride level ( ‐40 % , ‐29 % , and ‐8 % ) , high‐density lipoprotein cholesterol level ( 32 % , 30 % , and 7 % ) , use of insulin ( ‐35 % , ‐34 % , and ‐13 % ) , and quality ‐of‐life measures ( general health score increases of 17 , 16 , and 0.3 ; scores on the R AND 36‐Item Health Survey ranged from 0 to 100 , with higher scores indicating better health ) ( P comparisons ) . No major late surgical complications were reported except for one reoperation . CONCLUSIONS Five‐year outcome data showed that , among patients with type 2 diabetes and a BMI of 27 to 43 , bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing , or in some cases resolving , hyperglycemia . ( Funded by Ethicon Endo‐Surgery and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 .", "Two groups of beneficial bacteria are dominant in the human gut , the Bacteroidetes and the Firmicutes . Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people , and that this proportion increases with weight loss on two types of low-calorie diet . Our findings indicate that obesity has a microbial component , which might have potential therapeutic implication", "Complex gene – environment interactions are considered important in the development of obesity . The composition of the gut microbiota can determine the efficacy of energy harvest from food and changes in dietary composition have been associated with changes in the composition of gut microbial population s. The capacity to explore microbiota composition was markedly improved by the development of metagenomic approaches , which have already allowed production of the first human gut microbial gene catalogue and stratifying individuals by their gut genomic profile into different enterotypes , but the analyses were carried out mainly in non-intervention setting s. To investigate the temporal relationships between food intake , gut microbiota and metabolic and inflammatory phenotypes , we conducted diet-induced weight-loss and weight-stabilization interventions in a study sample of 38 obese and 11 overweight individuals . Here we report that individuals with reduced microbial gene richness ( 40 % ) present more pronounced dys-metabolism and low- grade inflammation , as observed concomitantly in the accompanying paper . Dietary intervention improves low gene richness and clinical phenotypes , but seems to be less efficient for inflammation variables in individuals with lower gene richness . Low gene richness may therefore have predictive potential for the efficacy of intervention", "CONTEXT It has been hypothesized that increased plasma bile acids ( BAs ) contribute to metabolic improvements after Roux-en-Y gastric bypass ( RYGB ) surgery by the G protein-coupled receptor TGR5-mediated effects on glucagon-like peptide-1 secretion and thyroid hormones . OBJECTIVE The objective of this study was to evaluate the importance of bariatric surgery-induced alterations in BA physiology on factors that regulate glucose homeostasis ( insulin secretion and sensitivity ) and energy metabolism ( resting energy expenditure and thyroid hormone axis ) . DESIGN , PARTICIPANTS , INTERVENTION , AND MAIN OUTCOME MEASURE : Eighteen extremely obese subjects were studied before and after 20 % weight loss , induced by either laparoscopic adjustable gastric b and ing ( LAGB ) ( n = 10 ) or RYGB surgery ( n = 8) . RESULTS Plasma BAs more than doubled after RYGB [ fasting : 1.08 ( 0.26 - 1.42 ) to 2.28 ( 1.59 - 3.28 ) μmol/L , P = .03 ; postpr and ial : 2.46 ± 1.59 to 6.00 ± 2.75 μmol/L , P = .01 ] but were either lower or did not change after LAGB [ fasting : 1.80 ( 1.49 - 2.19 ) to 0.92 ( 0.73 - 1.15 ) μmol/L , P = .02 ; postpr and ial : 3.71 ± 2.61 to 2.82 ± 1.75 μmol/L , P = .14 ] . Skeletal muscle expression of TGR5 targets , Kir6.2 and cyclooxygenase IV , increased after RYGB but not LAGB . Surgery-induced changes in BAs were associated with increased peak postpr and ial plasma glucagon-like peptide-1 ( r(2 ) = 0.509 , P = .001 ) and decreased serum TSH ( r(2 ) = 0.562 , P the change in insulin response to a meal ( r(2 ) = 0.013 , P = .658 ) , insulin sensitivity ( assessed as insulin stimulated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure ) ( r(2 ) = 0.001 , P = .995 ) , or resting energy expenditure ( r(2 ) = 0.004 , P = .807 ) . CONCLUSIONS Compared with LAGB , RYGB increases circulating BAs and TGR5 signaling , but this increase in BAs is not a significant predictor of changes in glucose homeostasis or energy metabolism" ]	4118615c-06ff-11f0-808a-c43d1ab1c353
Although clinical guidelines advocate exercise and activity in the management of non-specific low back pain ( NSLBP ) , the link between levels of physical activity and outcomes is unclear . This systematic review investigated the relationships between free living activity levels after onset of low back pain ( LBP ) and measures of pain , and disability in patients with NSLBP . Cohort and cross-sectional studies were located using OVID , CINAHL , Medline , AMED , Embase , Biomed , PubMed -National Library of Medicine , Proquest and Cochrane Data bases , and h and search es of reference lists . Studies were included if a statistical relationship was investigated between measures of free living physical activity ( PA ) in subjects with LBP and LBP outcome measures . Twelve studies ( seven cohort and five cross-sectional ) were included . One prospect i ve study reported a statistically significant relationship between increased leisure time activity and improved LBP outcomes , and one cross-sectional study found that lower levels of sporting activity were associated with higher levels of pain and disability . All other studies ( n = 10 ) found no relationship between measures of activity levels and either pain or disability . Heterogeneity of study design s , particularly in terms of activity measurement , made comparisons between studies difficult . These data suggest that the activity levels of patients with NSLBP are neither associated with , nor predictive of , disability or pain levels . Vali date d activity measurement in prospect i ve research is required to better evaluate the relationships between PA and LBP	[ "Study Design . A population -based cross-sectional and 5-year prospect i ve question naire study . Objective . To investigate self-reported physical workload as a risk factor for low back pain . Summary of Background Data . Both physical and psychosocial workplace factors are considered risk factors for low back pain . However , today no consensus has been reached regarding the exact role of these factors in the genesis of low back pain . Methods . Question naire data were collected at baseline for 1397 ( and after 5 years for 1163 ) men and women aged 31–50 years at baseline . Low back pain ( “ any low back pain within the past year , ” “ low back pain ≤ 30 days in total during the past year , ” “ low back pain > 30 days in total during the past year ” ) was analyzed in relation to physical workload ( sedentary , light physical , and heavy physical work ) using logistic regression and controlling for age , gender , and social group . The proportions of workers changing between the workload groups over the 5-year period were analyzed in relation to low back pain status . Results . At baseline no statistically significant differences in low back pain outcomes were found for workers exposed to sedentary , light physical , or heavy physical work . This was true for all age , gender , and social groups . At follow-up there was a statistically significant dose – response association between any low back pain and longst and ing low back pain within the past year and increasing physical workload at baseline also after controlling for age , gender , and social group . Subjects with heavy physical workload at baseline changed statistically significantly more often to sedentary work if they experienced low back pain for more than 30 days out of the past year . Conclusions . Having a sedentary job might have a protective or neutral effect in relation to low back pain , whereas having a heavy physical job constitutes a significant risk factor . Because of migration between exposure groups ( the “ healthy-worker ” effect ) , longitudinal studies are necessary for investigating the associations between physical workload and low back pain", "Study Design . Prospect i ve cohort study . Objectives . To investigate whether physical performance , grip strength , cognitive function , and depression symptomatology are risk factors for incident low back pain ( LBP ) over a 2-year period in seniors . Summary of Background Data . LBP is common in the older age groups , but little is known about predictors of LBP in this age group . Methods . Data from the 2001 and 2003 data collection from the population -based Longitudinal Study of Aging Danish Twins formed the basis of this analysis . Participants free from LBP at baseline ( no LBP during the past month , N = 1387 ) were included and interview data on overall physical function , and assessment of grip strength , overall cognitive function , and depression at baseline were obtained . LBP status at follow-up was assessed using a modified version of the St and ardized Nordic Question naire . Logistic regression was used to assess the associations between the baseline risk factors and LBP at follow-up . Results . A total of 1387 persons 70 to 100 years of age at baseline were included in the analyses . Of the initially LBP-free individuals , 7 % had experienced LBP more than 30 days out of the past year , 7 % had altered or decreased their physical activities due to LBP , and 11 % had received treatment for LBP at follow-up . Good overall physical function ( being among the top 50 % ) at baseline was protective for LBP of more than 30 days duration and for diminishing physical activities due to LBP and for care seeking due to LBP . High depression scores ( being among the top 25 % ) were strongly associated with altering or decreasing daily activities because of LBP . Grip strength and overall cognitive performance at baseline were associated with lower incidence of LBP and decreasing activities due to LBP at follow-up ; however , these associations were not statistically significant . Conclusion . Poor overall physical function and depression symptomatology are associated with LBP and consequences of LBP in persons 70 years of age and older", "Introduction : Behaviorally oriented grade d activity interventions have been suggested for sick-listed workers with low back pain on return to work , but have not been extensively evaluated . Methods : One hundred and thirty-four workers were r and omly assigned to either a grade d activity intervention ( n = 67 ) or usual care ( n = 67 ) and followed-up for 12 months . Results : The grade d activity group returned back to work faster with a median of 54 days compared to 67 days in the usual care group . The grade d activity intervention was more effective after approximately 50 days post-r and omization ( HRR = 1.9 , CI = 1.2–3.1 , p = 0.01 ) . Differences between the groups in number of recurrent episodes , total number of days of sick leave due to low back pain , and total number of days of sick leave due to all diagnoses , were in favor of the grade d activity group , although not statistically significant . No effects of the grade d activity intervention were found for functional status or pain . Conclusion : Grade d activity intervention is a valuable strategy to enhance short-term return to work outcomes", "OBJECTIVE To investigate the effectiveness of a TTM-based motivational counselling approach by trained practice nurses to promote physical activity of low back pain patients in a German primary care setting . METHODS Data were collected in a cluster-r and omized controlled trial with three study arms via question naires and patient interviews at baseline and after 6 and 12 months . We analysed total physical activity and self-efficacy by using r and om effect models to allow for clustering . RESULTS A total of 1378 low back pain patients , many with acute symptoms , were included in the study . Nearly 40 % of all patients reported sufficient physical activity at baseline . While there were significant improvements in patients ' physical activity behaviour in all study arms , there was no evidence for an intervention effect . CONCLUSION The outcome may be explained by insufficient performance of the practice nurses , implementation barriers caused by the German health care system and the heterogenous sample . PRACTICE IMPLICATION S Given the objective to incorporate practice nurses into patient education , there is a need for a better basic training of the nurses and for a change towards an organizational structure that facilitates patient-nurse communication . Counselling for low back pain patients has to consider more specificated aims for different subgroups", "Study Design . A 5-year prospect i ve cohort study was conducted of men and women seeking care for a new period of low back pain ( LBP ) . Objectives . To study the natural course of pain and disability due to LBP during a 5-year follow-up period , and to investigate the possible influence of regular physical exercise on recovery . Summary of Background Data . LBP is major health problem , but its natural course is not very well studied . Several studies have investigated the role of physical exercise on LBP disorders , with inconsistent results . Methods . At baseline , a total of 790 subjects seeking care for LBP were interviewed about physical exercise during leisure time . Over 5 years , 3 follow-up assessment s were made by postal question naire . At all measuring points , pain intensity ratings and disability scores were compared between men and women , and among 3 exercise categories . Results . The pain intensity and disability scores were improved after 5 years for both men and women . The most prominent improvements occurred after 6 months , but less so thereafter . There were no significant differences between men and women with regard to individual changes at the 5-year follow-up concerning the pain intensity or disability scores . There were no significant differences , either for women or men , between low , median , or high intensity exercise groups regarding pain intensity or disability values for the individual change at the 5-year follow-up . Conclusions . Over a 5-year period , both men and women who had sought care for LBP reported a decrease in pain and disability ; however , only a few were fully restored . In this study , we found no effect of nonspecific physical exercise on recovery from LBP in men and women", "Study Design . Prospect i ve case series with historical controls ( normative data ) . Objectives . To compare the aerobic fitness level of patients with chronic low back pain ( CLBP ) with healthy controls matched for gender , age , and level of sport activity and to evaluate the association of the difference in aerobic fitness level with pain intensity , duration and degree of disability , fear of injury , and level of activity during work , including household and leisure time . Summary and Background Data . Controversy exists whether patients with CLBP have a lower level of aerobic fitness and whether this level may partly depend on the patients ’ activity level . Methods . A total of 108 CLBP patients completed question naires regarding pain , disability , fear of injury , and activity level and performed a modified Åstr and submaximal cycling test . The maximum oxygen consumption ( VO2max ) was calculated and compared with normative data . Multiple linear regression analysis was performed with the difference of the level of aerobic fitness as dependent variable . Results . VO2max could be calculated in 78 % of the patients . Both men and women with CLBP had significant lower VO2max than the healthy referents ( 10 mL/kg LBM • min−1 and 5.6 mL/kg LBM • min−1 respectively , P the level of aerobic fitness was not associated with the presumed variables . The patients who stopped the test prematurely were older ( P = 0.02 ) and more disabled ( P = 0.01 ) . Conclusion . CLBP patients , especially men , seem to have a reduced aerobic fitness level compared with the normative population . No explanatory factor for that loss could be identified", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "BACKGROUND AND PURPOSE Therapeutic exercise has been shown to be beneficial in decreasing pain and in increasing functioning in patients with chronic low back pain . However , longitudinal follow-up studies are small in number , and often limited in the numbers of subjects due to drop-outs . In addition there is a shortage of real control groups in most cases . The purpose of the present study was to describe long-term changes in intensity of low back pain and in functioning for two study groups five years after undertaking a home exercise programme . METHOD This was a r and omized follow-up study over five years . Fifty-seven subjects were reassessed with question naires five years after their initial recruitment for an intervention study . A home exercise group ( n = 29 ) , with training once a day , and a control group ( n = 28 ) , without exercise , were included in the present study protocol . The primary outcome measurements included a question naire on the intensity of low back pain ( Borg CR-10 scale ) and on functioning ( Oswestry Disability Index ; ODI ) . The confounding physical activity was controlled with metabolic unit ( MET ) values . RESULTS The CR-10 and ODI scores decreased during the first three months in both study groups . During the follow-ups , the corresponding indicators of the home exercise group remained below baseline values . The CR-10 score was significantly lower in the home exercise group ( p = 0.01 ) during the last five-year follow-up session compared with the control group . Overall physical activity decreased slightly during the five-year follow-up , but there were no differences between the two study groups . CONCLUSIONS The present r and omized study indicates that supervised , controlled home exercises lead to reduced low back pain , and that positive effects were preserved over five years", "Study Design . Prospect i ve case series with historical controls ( normative data ) . Objectives . To compare aerobic fitness levels in patients with chronic low back pain with those published on a sample of 295 healthy subjects . Summary of Background Data . Clinical belief holds that patients with chronic low back pain have low fitness levels as a result of inactivity because of pain . Because few studies have investigated the level of aerobic fitness in these patients , however , it remains unclear how fitness levels in patients with chronic low back pain patients compare with those published a sample of the normative population . Methods . A sample of 50 patients with chronic low back pain with a mean pain duration of 40 months referred to an outpatient pain clinic performed a symptom-limited modified treadmill test . Aerobic fitness levels were determined by indirect calorimetry to measure oxygen consumption ( VO2 ) . Predicted maximum oxygen consumption ( VO2max ) levels were calculated for all subjects . Multiple regression analysis with adjustment for age and sex yielded prediction equations for men and women separately . Ninety-five percent confidence intervals were calculated for predicted mean oxygen consumption ( VO2 ) and the slope of the equations . These were compared to established prediction equations on healthy subjects . Results . Prediction equations for estimated maximum oxygen consumption ( VO2max ) in patients with chronic low back pain equal those in healthy sedentary men and active women . Conclusions . Levels of aerobic fitness in patients with chronic low back pain are comparable with those in healthy subjects", "Background : Low back pain is a common medical and social problem associated with disability and absence from work . Knowledge on effective return to work ( RTW ) interventions is scarce . Objective : To determine the effectiveness of grade d activity as part of a multistage RTW programme . Design : R and omised controlled trial . Setting : Occupational healthcare . Subjects : 112 workers absent from work for more than eight weeks due to low back pain were r and omised to either grade d activity ( n = 55 ) or usual care ( n = 57 ) . Intervention : Grade d activity , a physical exercise programme aim ed at RTW based on operant-conditioning behavioural principles . Main outcome measures : The number of days off work until first RTW for more then 28 days , total number of days on sick leave during follow up , functional status , and severity of pain . Follow up was 26 weeks . Results : Grade d activity prolonged RTW . Median time until RTW was equal to the total number of days on sick leave and was 139 ( IQR = 69 ) days in the grade d activity group and 111 ( IQR = 76 ) days in the usual care group ( hazard ratio = 0.52 , 95 % CI 0.32 to 0.86 ) . An interaction between a prior workplace intervention and grade d activity , together with a delay in the start of the grade d activity intervention , explained most of the delay in RTW ( hazard ratio = 0.86 , 95 % CI 0.40 to 1.84 without prior intervention and 0.39 , 95 % CI 0.19 to 0.81 with prior intervention ) . Grade d activity did not improve pain or functional status clinical ly significantly . Conclusions : Grade d activity was not effective for any of the outcome measures . Different interventions combined can lead to a delay in RTW . Delay in referral to grade d activity delays RTW . In implementing grade d activity special attention should be paid to the structure and process of care", "BACKGROUND In a pilot study for the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) a modification of the Baecke question naire on physical activity was tested for repeatability and relative validity in a population of 134 men and women aged 20 - 70 years . METHODS For the assessment of repeatability Pearson 's correlation coefficients and percentages of agreement after classification in tertiles were computed between administrations of the question naire at baseline , and after 5 and 11 months . Relative validity was determined by comparing the question naire to a four times repeated 3-day activity diary . RESULTS Repeatability after 5 and 11 months was good , with test-retest correlation coefficients between 0.65 and 0.89 for main sections of the question naire . The percentages of agreement , exceeding chance ( Cohen 's kappa ) were 57 % and 56 % for men ( at 5 and 11 months respectively ) and 41 % and 46 % for women . The correlations with the diaries were 0.56 in men and 0.44 in women . Agreement apart from chance between classification in tertiles for both methods was 35 % for men and 10 % for women . CONCLUSIONS These data show that repeatability is good and relative validity as compared to an activity diary is moderate but well within the range of values found in other studies . The question naire is more valid in men than in women", "OBJECTIVE To investigate whether personal and work-related factors , physical performance and back-specific question naires predict return to work . A prospect i ve study identifying prognostic factors for return to work . SUBJECTS Ninety-three patients sick-listed for 8 - 12 weeks for non-specific sub-acute low back pain included in a r and omized controlled trial . METHODS Patients were examined with regard to demographic variables , a battery of back-specific question naires and physical tests before entering a r and omized controlled trial . A stepwise backward Cox regression model was established to identify the most powerful predictors . RESULTS During follow-up 78.5 % of the patients have returned to full-time work . Fear-avoidance beliefs for work ( relative risk ( RR ) for 1 SD change 0.49 ; 95 % confidence interval ( CI ) 0.38 - 0.64 ) , disability ( RR 1.39 , 95 % CI 1.02 - 1.88 ) and cardiovascular fitness ( RR 1.42 , 95 % CI 1.12 - 1.79 ) were identified as the best predictors for return to work . The prevalence of correct predictions was 69.3 % . CONCLUSION The predictors identified in the present study may reflect personal risk factors in a patient who gets acute low back pain . On the other h and , they may support that fear of pain and injury may be more disabling than pain itself , and that deconditioning is a result of altered behaviour reflecting attitudes towards low back pain in society , and information and advice given in primary healthcare", "OBJECTIVES We sought to estimate the effects of recreational physical activity and back exercises on low back pain , related disability , and psychological distress among patients r and omized to chiropractic or medical care in a managed care setting . METHODS Low back pain patients ( n=681 ) were r and omized and followed for 18 months . Participation in recreational physical activities , use of back exercises , and low back pain , related disability , and psychological distress were measured at baseline , at 6 weeks , and at 6 , 12 , and 18 months . Multivariate logistic regression modeling was used to estimate adjusted associations of physical activity and back exercises with concurrent and subsequent pain , disability , and psychological distress . RESULTS Participation in recreational physical activities was inversely associated -- both cross-sectionally and longitudinally -- with low back pain , related disability , and psychological distress . By contrast , back exercise was positively associated -- both cross-sectionally and longitudinally -- with low back pain and related disability . CONCLUSIONS These results suggest that individuals with low back pain should refrain from specific back exercises and instead focus on nonspecific physical activities to reduce pain and improve psychological health", "Although r and omized controlled design s are considered the so-called gold st and ard in medical trials and sit atop the hierarchy of evidence in evidence -based medicine , there are situations in which they are impractical or unethical to undertake , especially in surgical trials . Then , observational studies often provide the best source of information . In this paper , we use examples from the literature to explain the importance of observational studies in furthering the boundaries of orthopaedic surgery and knowledge of musculoskeletal disorders", "Objective Research studies focussing on the fear-avoidance beliefs model ( FABM ) have exp and ed considerably during the last years , however , there has been very little research directed at the elderly . The objective of the present study was to investigate the validity of the FABM in older patients with chronic low back pain ( CLBP ) . Method In a cross-sectional study , a group of elderly patients with CLBP ( N=103 ) was compared with an age-matched group of pain-free individuals ( N=59 ) to test the constructs inherent in the FABM . Constructs include fear avoidance beliefs ( FABs ) , disability , disuse , and physical activity . In addition , the relationship of these constructs was also investigated in the patient group . CLBP- patients had an average age of 71.41 years ( SD=5.2 ) and pain-free individuals of 71.19 years ( SD=4.73 ) . Individuals participated in a photographed series of physical activities adapted to the age group ( Photograph Series of Daily Activities-German version for the elderly ) for the assessment of FAB , in the Hannover Disability Question naire , in the Freiburg Physical Activity Question naire , and in an ultrasound measurement to evaluate lumbar flexion . In addition , they completed an activity diary for 1 week . Before computation , the physical activity measurements were converted into metabolic units that characterize energy expenditure . Results In the patient group , FAB , pain intensity , and age predicted functional capacity , but not physical activity . Lumbar flexion was predicted by FAB and age . Patients were more fear-avoidant , reported more disability , and displayed less lumbar flexion than the pain-free individuals . No differences between the groups could be detected in regard to energy expenditure measured either by the question naire or by diary data . Conclusions The findings are consistent with results reported in the literature for younger age groups and confirm the assumption that the FABM is also valid for the elderly" ]	411861d4-06ff-11f0-808a-c43d1ab1c353
& NA ; An ever‐growing literature has aim ed to determine how individuals with autism spectrum disorder ( ASD ) differ from their typically developing ( TD ) peers on measures of multisensory integration ( MSI ) and to ascertain the degree to which differences in MSI are associated with the broad range of symptoms associated with ASD . Findings , however , have been highly variable across the studies carried out to date . The present work systematic ally review s and quantitatively synthesizes the large literature on audiovisual MSI in individuals with ASD to evaluate the cumulative evidence for ( a ) group differences between individuals with ASD and TD peers , ( b ) correlations between MSI and autism symptoms in individuals with ASD and ( c ) study level factors that may moderate findings ( i.e. , explain differential effects ) observed across studies . To identify eligible studies , a comprehensive search strategy was employed using the ProQuest search engine , PubMed data base , forwards and backwards citation search es , direct author contact , and h and ‐ search ing of select conference proceedings . A significant between‐group difference in MSI was evident in the literature , with individuals with ASD demonstrating worse audiovisual integration on average across studies compared to TD controls . This effect was moderated by mean participant age , such that between‐group differences were more pronounced in younger sample s. The mean correlation between MSI and autism and related symptomatology was also significant , indicating that increased audiovisual integration in individuals with ASD is associated with better language /communication abilities and /or reduced autism symptom severity in the extant literature . This effect was moderated by whether the stimuli were linguistic versus non‐linguistic in nature , such that correlation magnitudes tended to be significantly greater when linguistic stimuli were utilized in the measure of MSI . Limitations and future directions for primary and meta‐analytic research are discussed	[ "In dynamic cluttered environments , audition and vision may benefit from each other in determining what deserves further attention and what does not . We investigated the underlying neural mechanisms responsible for attentional guidance by audiovisual stimuli in such an environment . Event-related potentials ( ERPs ) were measured during visual search through dynamic displays consisting of line elements that r and omly changed orientation . Search accuracy improved when a target orientation change was synchronized with an auditory signal as compared to when the auditory signal was absent or synchronized with a distractor orientation change . The ERP data show that behavioral benefits were related to an early multisensory interaction over left parieto-occipital cortex ( 50 - 60 ms post-stimulus onset ) , which was followed by an early positive modulation ( 80 - 100 ms ) over occipital and temporal areas contralateral to the audiovisual event , an enhanced N2pc ( 210 - 250 ms ) , and a contralateral negative slow wave ( CNSW ) . The early multisensory interaction was correlated with behavioral search benefits , indicating that participants with a strong multisensory interaction benefited the most from the synchronized auditory signal . We suggest that an auditory signal enhances the neural response to a synchronized visual event , which increases the chances of selection in a multiple object environment ", "BACKGROUND It has frequently been suggested that individuals with autism spectrum disorder ( ASD ) have deficits in auditory-visual ( AV ) sensory integration . Studies of language integration have mostly used non-word syllables presented in congruent and incongruent AV combinations and demonstrated reduced influence of visual speech in individuals with ASD . The aim of our study was to test whether adolescents with high-functioning autism are able to integrate AV information of meaningful , phrase-length language in a task of onset asynchrony detection . METHODS Participants were 25 adolescents with ASD and 25 typically developing ( TD ) controls . The stimuli were video clips of complete phrases using simple , commonly occurring words . The clips were digitally manipulated to have the video precede the corresponding audio by 0 , 4 , 6 , 8 , 10 , 12 , or 14 video frames , a range of 0 - 500ms . Participants were shown the video clips in r and om order and asked to indicate whether each clip was in-synch or not . RESULTS There were no differences between adolescents with ASD and their TD peers in accuracy of onset asynchrony detection at any slip rate . CONCLUSION These data indicate that adolescents with ASD are able to integrate auditory and visual components in a task of onset asynchrony detection using natural , phrase-length language stimuli . We propose that the meaningful nature of the language stimuli in combination with presentation in a non-distracting environment allowed adolescents with autism spectrum disorder to demonstrate preserved accuracy for bi-modal AV integration", "BACKGROUND This project examined the intermodal perception of temporal synchrony in 16 young children ( ages 4 to 6 years ) with autism compared to a group of children without impairments matched on adaptive age , and a group of children with other developmental disabilities matched on chronological and adaptive age . METHOD A preferential looking paradigm was used , where participants viewed non-linguistic , simple linguistic or complex linguistic events on two screens displaying identical video tracks , but one offset from the other by 3 seconds , and with the single audio track matched to only one of the displays . RESULTS As predicted , both comparison groups demonstrated significant non-r and om preferential looking to violations of temporal synchrony with linguistic and non-linguistic stimuli . However , the group with autism showed an impaired , chance level of responding , except when presented with non-linguistic stimuli . CONCLUSIONS Several explanations are offered for this apparently autism-specific , language -specific pattern of responding to temporal synchrony , and potential developmental sequelae are discussed", "BACKGROUND During speech perception , the ability to integrate auditory and visual information causes speech to sound louder and be more intelligible , and leads to quicker processing . This integration is important in early language development , and also continues to affect speech comprehension throughout the lifespan . Previous research shows that individuals with autism have difficulty integrating information , especially across multiple sensory domains . METHODS In the present study , audiovisual speech integration was investigated in 18 adolescents with high-functioning autism and 19 well-matched adolescents with typical development using a speech in noise paradigm . Speech reception thresholds were calculated for auditory only and audiovisual matched speech , and lipreading ability was measured . RESULTS Compared to individuals with typical development , individuals with autism showed less benefit from the addition of visual information in audiovisual speech perception . We also found that individuals with autism were significantly worse than those in the comparison group at lipreading . Hierarchical regression demonstrated that group differences in the audiovisual condition , while influenced by auditory perception and especially by lipreading , were also attributable to a unique factor , which may reflect a specific deficit in audiovisual integration . CONCLUSIONS Combined deficits in audiovisual speech integration and lipreading in individuals with autism are likely to contribute to ongoing difficulties in speech comprehension , and may also be related to delays in early language development", "BACKGROUND Effective multisensory processing develops in infancy and is thought to be important for the perception of unified and multimodal objects and events . Previous research suggests impaired multisensory processing in autism , but its role in the early development of the disorder is yet uncertain . Here , using a prospect i ve longitudinal design , we tested whether reduced visual attention to audiovisual synchrony is an infant marker of later-emerging autism diagnosis . METHODS We studied 10-month-old siblings of children with autism using an eye tracking task previously used in studies of preschoolers . The task assessed the effect of manipulations of audiovisual synchrony on viewing patterns while the infants were observing point light displays of biological motion . We analyzed the gaze data recorded in infancy according to diagnostic status at 3 years of age ( DSM-5 ) . RESULTS Ten-month-old infants who later received an autism diagnosis did not orient to audiovisual synchrony expressed within biological motion . In contrast , both infants at low-risk and high-risk siblings without autism at follow-up had a strong preference for this type of information . No group differences were observed in terms of orienting to upright biological motion . CONCLUSIONS This study suggests that reduced orienting to audiovisual synchrony within biological motion is an early sign of autism . The findings support the view that poor multisensory processing could be an important antecedent marker of this neurodevelopmental condition", "Currently there are no brief , self-administered instruments for measuring the degree to which an adult with normal intelligence has the traits associated with the autistic spectrum . In this paper , we report on a new instrument to assess this : the Autism-Spectrum Quotient ( AQ ) . Individuals score in the range 0–50 . Four groups of subjects were assessed : Group 1 : 58 adults with Asperger syndrome ( AS ) or high-functioning autism ( HFA ) ; Group 2 : 174 r and omly selected controls . Group 3 : 840 students in Cambridge University ; and Group 4 : 16 winners of the UK Mathematics Olympiad . The adults with AS/HFA had a mean AQ score of 35.8 ( SD = 6.5 ) , significantly higher than Group 2 controls ( M = 16.4 , SD = 6.3 ) . 80 % of the adults with AS/HFA scored 32 + , versus 2 % of controls . Among the controls , men scored slightly but significantly higher than women . No women scored extremely highly ( AQ score 34 + ) whereas 4 % of men did so . Twice as many men ( 40 % ) as women ( 21 % ) scored at intermediate levels ( AQ score 20 + ) . Among the AS/HFA group , male and female scores did not differ significantly . The students in Cambridge University did not differ from the r and omly selected control group , but scientists ( including mathematicians ) scored significantly higher than both humanities and social sciences students , confirming an earlier study that autistic conditions are associated with scientific skills . Within the sciences , mathematicians scored highest . This was replicated in Group 4 , the Mathematics Olympiad winners scoring significantly higher than the male Cambridge humanities students . 6 % of the student sample scored 327plus ; on the AQ . On interview , 11 out of 11 of these met three or more DSM-IV criteria for AS/HFA , and all were study ing sciences/mathematics , and 7 of the 11 met threshold on these criteria . Test — retest and interrater reliability of the AQ was good . The AQ is thus a valuable instrument for rapidly quantifying where any given individual is situated on the continuum from autism to normality . Its potential for screening for autism spectrum conditions in adults of normal intelligence remains to be fully explored" ]	41186256-06ff-11f0-808a-c43d1ab1c353
Purpose of review New evidence for recommendations for vitamin D supplementation in healthy infants based upon recent literature . Recent findings R and omized controlled trials published since 2009 that related to vitamin D doses in infancy were review ed . They do not provide any additional evidence that larger , more generous amounts of daily vitamin D beyond the customary recommended 400 IU daily dose , affect any significant outcome . Larger amounts may lead to serum 25 hydroxy vitamin D concentrations that have been reported to be potentially associated with adverse effects . Summary There are still many unanswered questions left , in particular whether or not more ‘ generous ’ amounts of vitamin D in infancy may improve long-term health outcomes such as prevention of osteoporosis , allergies , or cancer	[ "Summary Whether infant vitamin D supplementation may have long-term bone benefits is unclear . In this study , breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years . This study provides important data to inform pediatric public health recommendations for vitamin D. Introduction North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health . Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization . The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation , vitamin D status , and bone outcomes at 3 years of age . Methods This was a double-blind r and omized trial of 132 , 1-month-old healthy , breastfed infants from Montréal , Canada , between 2007 and 2010 . In this longitudinal analysis , 87 infants ( 66 % ) returned for follow-up at 3 years of age , between 2010 and 2013 . At 1 month of age , participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 , 800 , 1200 , or 1600 IU/day until 12 months of age . Lumbar spine vertebrae 1–4 ( LS ) bone mineral density ( BMD ) , LS and whole body bone mineral content ( BMC ) , and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years . Results At follow-up , the treatment groups were similar in terms of diet , sun exposure , and demographics . There were no significant differences among the groups in LS or whole body BMC , BMD , or accretion . Although , 25(OH)D concentrations were not different among the groups , higher doses ( 1200 and 1600 IU/day ) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day . Conclusions This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age . Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up . Larger studies with more ethnically diverse groups are needed to confirm these results", "The daily supplementation of vitamin D is m and atory for infants . However , there are still conflicting opinions about the exact daily dose . Thus , we aim ed to evaluate a daily supplementation dose of 200 IU is sufficient and compared the supplementation doses of 200 and 400 IU per day . One hundred and sixty-nine infants were r and omly assigned to two groups ( group1 , 200 IU/day ; group 2 , 400 IU/day ) and there were 75 infants in group 1 and 64 were in group 2 with a total number of 139 . The median levels of 25-hydroxyvitamin D3 were significantly increased in group 2 at the age of 4 months ( group 1 , 39.60 mcg/L ; group 2 , 56.55 mcg/L ; p serum level of 25-hydroxyvitamin D3 less than 30 mcg/L. However , 21.3 % of the infants in group 1 had a level below 30 mcg/L. Thus , in order to avoid vitamin D deficiency and rickets , we recommend supplementation dose of vitamin D at 400 IU/day as a safe and effective dose", "IMPORTANCE Vitamin D supplementation in infancy is required to support healthy bone mineral accretion . A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D ( 25[OH]D ) concentrations between 40 and 50 nmol/L ; some advocate 75 to 150 nmol/L for bone health . OBJECTIVE To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants . DESIGN , SETTING , AND PARTICIPANTS Double-blind r and omized clinical trial conducted among 132 one-month-old healthy , term , breastfed infants from Montréal , Québec , Canada , between March 2007 and August 2010 . Infants were followed up for 11 months ending August 2011 ( 74 % completed study ) . INTERVENTION Participants were r and omly assigned to receive oral cholecalciferol ( vitamin D3 ) supplements of 400 IU/d ( n=39 ) , 800 IU/d ( n=39 ) , 1200 IU/d ( n=38 ) , or 1600 IU/d ( n=16 ) . MAIN OUTCOMES AND MEASURES The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5 % of infants at 3 months . Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5 % of infants at 6 , 9 , and 12 months ; 25(OH)D concentrations of 50 nmol/L or greater across all times ; growth ; and whole body and regional bone mineral content . Data were analyzed by intention to treat using available data , logistic regression , and mixed-model analysis of variance . RESULTS By 3 months , 55 % ( 95 % CI , 38%-72 % ) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95 % CI , 65%-91 % ) in the 800-IU/d group , 92 % ( 95 % CI , 77%-98 % ) in the 1200-IU/d group , and 100 % in the 1600-IU/d group . This concentration was not sustained in 97.5 % of infants at 12 months in any of the groups . The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations . All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97 % ( 95 % CI , 94%-100 % ) of infants at 3 months and sustained this in 98 % ( 95 % CI , 94%-100 % ) to 12 months . Growth and bone mineral content did not differ by dosage . CONCLUSIONS AND RELEVANCE Among healthy , term , breastfed infants , only a vitamin D supplement dosage of 1600 IU/d ( but not dosages of 400 , 800 , or 1200 IU/d ) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5 % of infants at 3 months . However , this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00381914", "Background The rate of non-compliance with vitamin D supplementation is as high as 45 % . This is why r and omised controlled trials are needed to analyse the response to low doses of vitamin D3 . Objective ( 1 ) To compare supplementation with 250 versus 500 units of vitamin D3 and ( 2 ) to analyse sun exposure time/ultraviolet B ( UVB ) exposure during the first 6 weeks of life . Design 40 breastfed infants ( skin photo-types I , II ) were recruited in Berlin , Germany ( 52.5 ° N ) , during summer ( n=20 ) and winter ( n=20 ) and r and omised into equal groups on either 250 or 500 units of vitamin D3 per day . Outcome measures were : parameters of vitamin D and bone metabolism at delivery and 6 weeks later , sun exposure time , UVB dosimetry and surrounding factors including maternal diet . Results At delivery 25-hydroxy vitamin D levels were insufficient : 68 ( 53–83 ) nmol/l in each group . 6 weeks later levels were sufficient : 139 ( 114–164 ) nmol/l on 250 units of vitamin D3 per day and 151 ( 126–176 ) nmol/l on 500 units/day . There was no seasonal variation . Daily sun exposure time was 0.4–3.5 h and higher in summer . UVB exposure was 0.01–0.08 minimal erythema dose/day . Calcium levels were within normal . Conclusions In Berlin , Germany , supplementation with 250 units of vitamin D3 is sufficient for breastfed infants during their first 6 weeks of life in summer and winter . UVB exposure is very low throughout the year", "The biological equivalency of ergocalciferol ( D2 ) and cholecalciferol ( D3 ) has been debated ; several comparisons have appeared in the adult literature but are scarce in pediatrics . The objective of this study was to compare increases in plasma 25-hydroxyvitamin D [ 25(OH)D ] concentrations and attainment of 50 and 75 mol/L status cutoffs following 3 mo of daily supplementation with D2 compared with D3 . Healthy , breast-fed , 1-mo-old infants ( n = 52 ) received 10 μg ( 400 ic ) of either D2 or D3 daily . At 1 and 4 mo of age , plasma 25-hydroxyergocalciferol and 25-hydroxycholecalciferol concentrations were determined by liquid chromatography t and em MS ( LC-MS/MS ) and total 25(OH)D by chemiluminescent immunoassay ( DiaSorin Liaison ) . Data were analyzed using t tests and χ2 by intent to treat . A total of 23 % of infants were deficient ( ≤24.9 nmol/L ) at baseline and 2 % at follow-up on the basis of LC-MS/MS . At 4 mo , 96 % were breastfed and there were no differences in compliance , breastfeeding rates , or sun exposure among groups . The change in total 25(OH)D measured by LC-MS/MS did not differ between the D2 ( 17.6 ± 26.7 nmol/L ) and D3 ( 22.2 ± 20.2 nmol/L ) groups . In the combined groups , the baseline plasma 25(OH)D concentration was inversely related to the change in total 25(OH)D ( r = −0.52 ; P the increase in the 25(OH)D concentration among the D2 and D3 groups did not differ , suggesting daily intake of either isoform is acceptable for infants < 4 mo", "OBJECTIVE : To investigate the effect of vitamin D3 supplementation on the incidence and risk for first and recurrent diarrheal illnesses among children in Kabul , Afghanistan . METHODS : This double-blind placebo-controlled trial r and omized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses of oral vitamin D3 ( cholecalciferol 100 000 IU ) or placebo in inner city Kabul . Data on diarrheal episodes ( ≥3 loose/liquid stools in 24 hours ) was gathered through active and passive surveillance over 18 months of follow-up . Time to first diarrheal illness was analyzed by using Kaplan-Meier plots . Incidence rates and hazard ratios ( HRs ) were calculated by using recurrent event Poisson regression models . RESULTS : No significant difference existed in survival time to first diarrheal illness ( log rank P = .55 ) . The incidences of diarrheal episodes were 3.43 ( 95 % confidence interval [ CI ] , 3.28–3.59 ) and 3.59 per child-year ( 95 % CI , 3.44–3.76 ) in the placebo and intervention arms , respectively . Vitamin D3 supplementation was found to have no effect on the risk for recurrent diarrheal disease in either intention-to-treat ( HR , 1.05 ; 95 % CI , 0.98–1.17 ; P = .15 ) or per protocol ( HR , 1.05 ; 95 % CI , 0.98–1.12 ; P = .14 ) analyses . The lack of preventive benefit remained when the r and omized population was stratified by age groups , nutritional status , and seasons . CONCLUSIONS : Quarterly supplementation with vitamin D3 conferred no reduction on time to first illness or on the risk for recurrent diarrheal disease in this study . Similar supplementation to comparable population s is not recommended . Additional research in alternative setting s may be helpful in elucidating the role of vitamin D3 supplementation for prevention of diarrheal diseases", "INTRODUCTION The present study was design ed to compare two methods of vitamin D supplementation in infants : every two months as a routine vaccination versus a daily dose . METHODS A r and omised clinical trial was performed on 120 healthy breastfed infants between January and September 2007 in Yazd , Iran . The infants were r and omly divided into three groups with different doses of vitamin D3 supplementation : 200 IU daily , 400 IU daily and a bolus of 50,000 IU every two months . A blood sample was taken and evaluated for 25-hydroxy vitamin D and calcium levels when the infants were six months old . The data was reported as the mean and st and ard deviation . RESULTS No significant differences were observed between the serum level of 25-hydroxy vitamin D in the groups administered with 200 IU and 400 IU vitamin D daily . However , the serum level of 25-hydroxy vitamin D reached significance in the third group ( p is less than 0.001 ) . All the blood calcium measured was below 11 mg/dl in the bolus group . A few complications such as diarrhoea and agitation , all of which were self-limited , were seen in the bolus group . No other significant side effects were reported in the other groups . CONCLUSION This study demonstrates that a bolus of 50,000 IU of vitamin D every two months with a routine child vaccination program provides the ideal serum level of vitamin D. This method produces no serious side effects and offers a highly convenient way to supply vitamin D , especially among non-compliant parents", "This study was conducted to determine if vitamin D supplementation is required to prevent rickets in breast-fed infants . Breast-feeding rates are increasing , and there are concerns about whether the vitamin D content of breast milk is sufficient . There are a few treatment trials of vitamin D supplementation in breast-fed infants ; these were conducted in northern climates . The authors therefore performed a prospect i ve clinical trial comparing vitamin D supplementation with placebo as control in southern Louisiana . Blood sample s and question naires were collected at birth , 2 , 4 , and 6 months of age . There were no cases of rickets observed , and no differences in alkaline phosphatase levels between groups . Thus , there was no evidence that vitamin D supplementation reduced rickets risk in the authors ’ study population . This suggests that the current recommendations for universal vitamin D supplementation of breast-fed infants throughout the United States may need to be revised", "The objective was to evaluate the need for vitamin D prophylaxis in healthy infants . This was a prospect i ve and r and omized study performed at primary care clinics . Eighty-eight full-term 1-month-old healthy infants were r and omly assigned to receive ( n = 41 ) or not ( n = 47 ) 402 IU/d of vitamin D for 1 year . Primary outcome measures were serum 25-hydroxyvitamin D ( 25OHD ) and parathyroid hormone ( PTH ) concentrations at 3 , 6 , and 12 months of age ; secondary measures included data on feeding , habitat , season of birth , sun exposure , and physical examination . At 3 and 6 months of age , serum 25OHD levels ( ±SD ) were significantly higher ( P prophylaxis , serum 25OHD increased with age ; and breast-fed infants aged 3 months had the lowest value ( 20.2 ± 9.4 ng/mL ) , which was significantly ( P = .001 ) lower than that of formula-fed infants ( 35.0 ± 9.7 ng/mL ) . The PTH levels were not influenced by the prophylaxis or feeding . No influence of either the habitat or season of birth on serum 25OHD concentrations was demonstrated . No infant had clinical signs of vitamin D deficiency . Serum 25OHD and PTH concentrations were weakly but significantly correlated ( r = -0.29 , P = .009 ) at 3 months of age . Healthy infants without vitamin D prophylaxis had lower circulating concentrations of 25OHD at 3 and 6 months of age , the lowest value being found in 3-month breast-fed infants . The clinical relevance of these findings is probably negligible because serum 25OHD levels spontaneously increased with age and were not associated with high serum PTH . Clinical manifestations of rickets were not observed", "CONTEXT Guidelines in Finl and recommend 10 μg of vitamin D3 daily for all infants . Recent observations suggest that this may be insufficient to maintain optimal serum 25-hydroxyvitamin D ( S-25-OHD ) . OBJECTIVE The aim of the study was to evaluate effects of various vitamin D doses and determine a dose ensuring S-25-OHD of at least 80 nmol/liter in infants without signs of vitamin D excess . DESIGN We conducted a r and omized double-blind intervention study . Cord blood was obtained at birth for S-25-OHD ; 113 infants were r and omized to receive vitamin D3 10 , 30 , or 40 μg/d from age 2 wk to 3 months . SETTING An investigator-initiated study was performed in a single maternity hospital in Helsinki , Finl and . MAIN OUTCOME MEASURES S-25-OHD , calcium homeostasis , and skeletal characteristics were evaluated with peripheral quantitative computed tomography at age 3 months . RESULTS Baseline S-25-OHD was similar in all three groups ( median , 53 nmol/liter ) . At 3 months , the mean S-25-OHD values were 88 , 124 , and 153 nmol/liter , and the minimum values were 46 , 57 , and 86 nmol/liter in the groups receiving 10 , 30 , and 40 μg ( ANOVA ; P No hypercalcemia occurred ; plasma calcium , serum PTH , and urine calcium excretion was similar between the groups . Peripheral quantitative computed tomography showed a trend toward larger tibial total bone and cortical bone area with higher vitamin D doses . CONCLUSION Vitamin D3 supplementation with up to 40 μg/d from age 2 wk to 3 months was safe and caused no hypercalcemia or hypercalciuria . The 40-μg dose maintained S-25-OHD above 80 nmol/liter in all infants . More extensive and longer intervention studies are necessary to assess long-term effects", "BACKGROUND The impact of vitamin D status on body composition is not well understood . OBJECTIVES Evaluate how vitamin D supplementation in infancy affects body composition at 3 years of age . METHODS Double-blind r and omized trial of 132 , 1-month-old healthy , breastfed infants r and omly assigned to receive oral vitamin D3 supplements of 400 , 800 , 1200 or 1600 IU d-1 for 11 months . In the present analysis , 87 ( 66 % ) returned at 3 years of age . Body composition was measured using dual-energy x-ray absorptiometry and plasma 25-hydroxyvitamin D [ 25(OH)D ] concentrations by liquid chromatography t and em mass spectrometry . RESULTS Anthropometry , body composition , diet , activity and demographics were similar across dosage groups at 3 years . Mean 25(OH)D concentration from 1 month to 3 years was higher ( P lower fat mass ( ~450 g ; P = 0.049 ) . In multiple linear regression , mean 25(OH)D was associated with lean mass percent ( β = 0.06 ; CI : 0.00 , 0.12 ; P = 0.042 ) , fat mass ( β = -11.29 ; CI : -22.06 , -0.52 ; P = 0.048 ) and body fat percent ( β = -0.06 ; CI : -0.12 , -0.01 ; P = 0.045 ) . CONCLUSIONS Higher vitamin D status from infancy through to 3 years of age associates with leaner body composition " ]	411862ce-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Guidelines recommend implementation of multimodal interventions to help prevent recurrent TIA/stroke . We undertook a systematic review to assess the effectiveness of behavioral secondary prevention interventions . STRATEGY Search es were conducted in 14 data bases , including MEDLINE ( 1980-January 2014 ) . We included r and omized controlled trials ( RCTs ) testing multimodal interventions against usual care/modified usual care . All review processes were conducted in accordance with Cochrane guidelines . RESULTS Twenty-three papers reporting 20 RCTs ( 6,373 participants ) of a range of multimodal behavioral interventions were included . Method ological quality was generally low . Meta-analyses were possible for physiological , lifestyle , psychosocial and mortality/recurrence outcomes . Note : all reported confidence intervals are 95 % . Systolic blood pressure was reduced by 4.21 mmHg ( mean ) ( -6.24 to -2.18 , P = 0.01 I2 = 58 % , 1,407 participants ) ; diastolic blood pressure by 2.03 mmHg ( mean ) ( -3.19 to -0.87 , P = 0.004 , I2 = 52 % , 1,407 participants ) . No significant changes were found for HDL , LDL , total cholesterol , fasting blood glucose , high sensitivity-CR , BMI , weight or waist : hip ratio , although there was a significant reduction in waist circumference ( -6.69 cm , -11.44 to -1.93 , P = 0.006 , I2 = 0 % , 96 participants ) . There was no significant difference in smoking continuance , or improved fruit and vegetable consumption . There was a significant difference in compliance with antithrombotic medication ( OR 1.45 , 1.21 to 1.75 , P with statins ( OR 2.53 , 2.15 to 2.97 , P compliance with antihypertensives . There was a significant reduction in anxiety ( -1.20 , -1.77 to -0.63 , P odds of death or recurrent TIA/stroke , there was a significant reduction in the odds of cardiac events ( OR 0.38 , 0.16 to 0.88 , P = 0.02 , I2 = 0 % , 4,053 participants ) . CONCLUSIONS There are benefits to be derived from multimodal secondary prevention interventions . However , the findings are complex and should be interpreted with caution . Further , high quality trials providing comprehensive detail of interventions and outcomes , are required . REVIEW REGISTRATION PROSPERO CRD42012002538	[ "Background and Purpose — High rates of ischemic stroke and poor adherence to secondary prevention measures are observed in the Chinese population . Methods — We used a national , multicenter , cluster-r and omized controlled trial in which 47 hospitals were r and omized to either a structured care program group ( n=23 ) or a usual care group ( n=24 ) . The structured care program consisted of a specialist-administered , guideline -recommended pharmaceutical treatment and a lifestyle modification algorithm associated with written and Internet-accessed educational material for patients for the secondary prevention of ischemic stroke . The primary efficacy outcome was the proportion of patients who adhered to the recommended measures at 12-month postdischarge . This trial is registered with Clinical Trial.gov ( NCT00664846 ) . Results — At 12 months , 1287 ( 72.1 % ) patients in the St and ard Medical Management in Secondary Prevention of Ischemic Stroke in China ( SMART ) group and 1430 ( 72 % ) patients in the usual care group had completed the 12-month follow-up ( P=0.342 ) . Compared with the usual care group , those in the SMART group showed higher adherence to statins ( 56 % versus 33 % ; P=0.006 ) but no difference in adherence to antiplatelet ( 81 % versus 75 % ; P=0.088 ) , antihypertensive ( 67 % versus 69 % ; P=0.661 ) , or diabetes mellitus drugs ( 73 % versus 67 % ; P=0.297 ) . No significant difference in the composite end point ( new-onset ischemic stroke , hemorrhagic stroke , acute coronary syndrome , and all-cause death ) was observed ( 3.56 % versus 3.59 % ; P=0.921 ) . Conclusions — The implementation of a program to improve adherence to secondary ischemic stroke prevention efforts in China is feasible , but these programs had only a limited impact on adherence and no impact on 1-year outcomes . Further development of a structured program to reduce vascular events after stroke is needed . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00664846", "Objective : Despite evidence demonstrating that risk-factor management is effective in reducing recurrent cerebrovascular disease , there are very few structured care programmes for stroke survivors . The aim was to implement and evaluate an integrated care programme in stroke . Methods : 186 patients with stroke were r and omised to either the treatment ( integrated care ) or control ( usual care ) group and were followed up over 12 months . The Integrated Care for the Reduction of Secondary Stroke ( ICARUSS ) model of integrated care involved collaboration between a specialist stroke service , a hospital coordinator and a patient ’s general practitioner . The primary aim was to promote the management of vascular risk factors through ongoing patient contact and education . Results : In the 12 months poststroke , systolic blood pressure ( sBP ) decreased in the treatment group but increased in controls . The group difference was significant , and remained so when age , sex , disability and sBP at discharge were accounted for ( p = 0.04 ) . Treatment patients also exhibited better modification of body mass index ( p = 0.007 ) and number of walks taken ( p controls . Rankin scores indicated significantly reduced disability in treatment patients relative to controls in the year poststroke ( p = 0.003 ) . Conclusions : Through an integrated system of education , advice and support to both patient and GP , the ICARUSS model was effective in modifying a variety of vascular risk factors and therefore should decrease the likelihood or recurrent stroke or vascular event", "Objective The purpose of this study is to identify factors which predict adherence in stroke survivors . Design This is a longitudinal study where 180 stroke survivors were assessed 1 year after their first ischaemic stroke . The relationship between adherence and illness and medication beliefs was tested at baseline ( time 1 ) and again 5–6 weeks later ( time 2).Main Outcome Measures The main outcome measures used in this study are Medication Adherence Report Scale and urinary salicylate levels . Results Four variables predicted time 1 poor adherence : ( 1 ) younger age , ( 2 ) increased specific concerns about medications , ( 3 ) reduced cognitive functioning and ( 4 ) low perceived benefit of medication . Three out of these four variables were again predictive of time 2 adherence and accounted for 24 % of the variance : ( 1 ) younger age , ( 2 ) increased specific concerns about medications and ( 3 ) low perceived benefit of medication . The urinary salicylate assay failed to differentiate between patients taking and not taking aspirin . Conclusion Interventions to improve adherence should target patients ’ beliefs about their medication", "Objective Tailoring stroke information and providing reinforcement opportunities are two strategies proposed to enhance the effectiveness of education . This study aim ed to evaluate the effects of an education package which utilised both strategies on the knowledge , health and psychosocial outcomes of stroke patients and carers . Design Multisite , r and omised trial comparing usual care with an education and support package . Setting Two acute stroke units . Participants Patients and their carers ( N=138 ) were r and omised ( control n=67 , intervention n=71 ) of which data for 119 participants ( control n=59 , intervention n=60 ) were analysed . Intervention The package consisted of a computer-generated , tailored written information booklet and verbal reinforcement provided prior to , and for 3 months following , discharge . Outcome measures Outcome measures were administered prior to hospital discharge and at 3-month follow-up by blinded assessors . The primary outcome was stroke knowledge ( score range : 0–25 ) . Secondary outcomes were : self-efficacy ( 1–10 ) , anxiety and depression ( 0–21 ) , ratings of importance of information ( 1–10 ) , feelings of being informed ( 1–10 ) , satisfaction with information ( 1–10 ) , caregiver burden ( carers ) ( 0–13 ) and quality of life ( patients ) ( 1–5 ) . Results Intervention group participants reported better : self-efficacy for accessing stroke information ( adjusted mean difference ( MD ) of 1.0 , 95 % CI 0.3 to 1.7 , p=0.004 ) ; feeling informed ( MD 0.9 , 95 % CI 0.2 to 1.6 , p=0.008 ) ; and satisfaction with medical ( MD 2.0 , 95 % CI 1.1 to 2.8 , p practical ( MD 1.1 , 95 % CI 0.3 to 1.9 , p=0.008 ) , services and benefits ( MD 0.9 , 95 % CI 0.1 to 1.8 , p=0.036 ) and secondary prevention information ( MD 1.7 , 95 % CI 0.9 to 2.5 , p Conclusions Intervention group participants had improved self-efficacy for accessing stroke information and satisfaction with information , but other outcomes were not significantly affected . Evaluation of a more intensive intervention in a trial with a larger sample size is required to establish the value of an educational intervention that uses tailoring and reinforcement strategies .", "AIM To assess the feasibility of recruiting and retaining patients newly diagnosed with a Transient Ischaemic Attack ( TIA ) into an 8-week exercise programme . METHODS The study was a single-centre , r and omised-controlled trial . TIA was confirmed by a specialist stroke physician within 7 days of symptom onset . Following baseline assessment , participants were r and omised to either an 8-week exercise intervention or control group ( usual care ) . Participants completed a further assessment 2 months after baseline . RESULTS Of the 285 individuals diagnosed with TIA , 97 patients were invited to participate in the trial , of which 60 were successfully recruited ( 62 % ) . Of those invited , 89 % were identified within outpatient care . Individuals were typically of European descent ( 87 % ) and lived within 20 km of the study site ( 81 % ) . Distance to travel was considered the primary barrier for non-participation ( 46 % ) . Three participants ( 5 % ) did not attend the follow-up assessment . CONCLUSION Individuals with TIA were successfully recruited and retained into a RCT . A different approach is required to study interventions in Maori , Pacific Isl and ers , Asian and Indian population s. If the exercise intervention improves vascular risk factors and reduces recurrent vascular events , it could be applied to a large number of people who suffer a TIA or non-disabling stroke", "BACKGROUND The highest risk for stroke is among survivors of strokes or transient ischemic attacks ( TIA ) . However , use of proven-effective cardiovascular medications to control stroke risk is suboptimal , particularly among the Black and Latino population s disproportionately impacted by stroke . METHODS A partnership of Harlem and Bronx community representatives , stroke survivors , research ers , clinicians , outreach workers and patient educators used community-based participatory research to conceive and develop the Prevent Recurrence of All Inner-city Strokes through Education ( PRAISE ) trial . Using data from focus groups with stroke survivors , they tailored a peer-led , community-based chronic disease self-management program to address stroke risk factors . PRAISE will test , in a r and omized controlled trial , whether this stroke education intervention improves blood pressure control and a composite outcome of blood pressure control , lipid control , and use of antithrombotic medications . RESULTS Of the 582 survivors of stroke and TIA enrolled thus far , 81 % are Black or Latino and 56 % have an annual income less than $ 15,000 . Many ( 33 % ) do not have blood pressures in the target range , and most ( 66 % ) do not have control of all three major stroke risk factors . CONCLUSIONS Rates of stroke recurrence risk factors remain suboptimal in the high risk , urban , predominantly minority communities studied . With a community-partnered approach , PRAISE has recruited a large number of stroke and TIA survivors to date , and may prove successful in engaging those at highest risk for stroke and reducing disparities in stroke outcomes in inner-city communities", "BACKGROUND hypertension is a common risk factor for stroke/transient ischaemic attack ( TIA ) and there is good evidence that blood pressure ( BP ) control prevents recurrent stroke . We investigated whether telephone follow-up ( TFU ) improved risk factor management in hypertensive patients after stroke/TIA . METHODS we conducted a r and omised controlled trial and assigned hypertensive patients within 1 month of stroke or TIA to receive usual care ( n = 27 ) or usual care plus regular TFU ( n = 29 ) . Primary outcome was the difference in 12 h ambulatory systolic BP change from baseline to 6 months ( DeltaSBP ) in both groups . TFU at 7 days , 1 , 2 and 4 months included patient-focussed education and goal setting . RESULTS mean baseline BP was 145/83 mm Hg ( st and ard deviation ( SD ) 21/14 ) . There was no significant difference in DeltaSBP over 6 months with TFU . Median DeltaSBP was 0 mm Hg ( interquartile range 19.5 ) in the TFU group and 3.0 mm Hg ( 20 ) fall in the usual care group ( P = 0.29 ) . Post hoc analysis showed that statin use increased from baseline to 6 months ( P = 0.02 ) and cholesterol was significantly lower at 6 months in all patients ( mean reduction 0.95 mmol/l ; P BP control over 6-month follow-up in primary care after stroke/TIA", "Objective : Little is known about the long-term effectiveness after stroke of interventions for behaviour modification and ensuring concordance with therapies . We describe a follow-up study of a previous r and omized controlled trial of a brief period of behaviour modification . The aim of this study was to determine outcomes three years after the initial intervention . Design : Survivors of the original cohort were contacted and asked to attend for follow-up interview , within a geriatric day hospital . This study was carried out in the Geriatric Day Hospital at Stobhill Hospital , Balornock Road , Glasgow . Interventions : Details of risk factor control , including blood pressure , cholesterol levels and diabetic control , were assessed . Question naires used in the initial study were repeated including the Geriatric Depression Scale score , Euroqol Perceived Health Status and Stroke Services Satisfaction Question naire . Main measures : Primary outcome was collective risk factor control . Clinical outcomes including recurrent cerebrovascular events , medication persistence and perceived health status were also recorded . Results : Mean length of follow-up was 3.6 years ( SD 0.43 ) . Of the 205 patients enrolled in the initial study , 102 patients attended for repeat interview ( 49 intervention/53 control ) . There were no significant differences in the percentage of controlled risk factors between groups ( intervention 51.7 % versus control 55.9 % , P = 0.53 ) . Similarities were observed in the number of recurrent clinical events and medication persistence between groups . No overall difference was observed in perceived health status , satisfaction with care or depression scores . Conclusions : Brief intervention with respect to behaviour modification and risk factor control does not appear to have any long-term benefit . These results must be cautiously interpreted in light of the small study number and further research is required", "Objective : To evaluate the feasibility and effectiveness of a st and ard National Health Service cardiac rehabilitation programme on risk factor reduction for patients after a minor stroke and transient ischaemic attack . Design : Single-blind r and omized controlled trial . Setting : Cardiac rehabilitation classes . Subjects : Twenty-four patients . Intervention : All participants received st and ard care . In addition , the intervention group undertook an eight-week cardiac rehabilitation programme consisting of weekly exercise and education classes . Outcome measures : Cardiovascular disease risk score ; lipid profiles ; resting blood pressure ; C-reactive protein ( measured with a high sensitive assay ) and fibrinogen levels ; blood glucose ; obesity ; physical activity levels ; subjective health status ( SF-36 ) ; Hospital Anxiety and Depression Scale . Results : Group comparison with independent t-tests showed a significantly greater improvement in the cardiovascular disease risk score for participants in the intervention group compared to st and ard care ( intervention 25.7 ± 22.8 to 23.15 ± 18.3 , control 25.03 ± 15.4 to 27.12 ± 16.1 , t = −1.81 , P in activity levels ( intervention 9.41 ± 7.7 to 8.08 ± 5.7 , control 14.50 ± 5.5 to 9.83 ± 6.6 , t = −2.00 , P 0.05 ) and the SF-36 domains of physical functioning ( intervention 70 ± 24.6 to 75.4 ± 11.1 , control 90.00 ± 12.4 to 83.16 ± 17.3 , t = −2.72 , P 0.05 ) and mental health ( intervention 84 ± 40 to 92 ± 40 , control 88.00 ± 60 to 84 ± 44 , z = −2.06 , P suggest that st and ard cardiac rehabilitation programmes are a feasible and effective means of reducing the risk of future cardiovascular events for patients after minor stroke and transient ischaemic attack", "Objective : To evaluate whether enhanced secondary prevention more significantly influences readiness to change health behaviour after minor stroke/transient ischaemic attack , compared with conventional stroke secondary prevention . Design : Single-blind r and omized control trial . Setting : Rural district general hospital outpatient clinic . Subjects : Fifteen women and 37 men with a mean age of 68.3 years with first minor stroke or transient ischaemic attack . Interventions : The intervention group received ‘ enhanced secondary prevention ’ ( additional advice , motivational interviewing and telephone support ) to change health behaviour . Both groups received ‘ conventional care ’ which included advice given during routine care . Main measures : The primary outcome was ‘ readiness to change behaviour ’ measured using a vali date d stroke specific score based on the transtheoretical model . Secondary outcomes were the Hospital Anxiety and Depression Scale , and self-reported alcohol consumption , smoking behaviour , exercise frequency , and fruit and vegetable consumption . Results : Analysis of the data for the 52 participants showed no statistical difference in the groups for the primary outcome of readiness to change behaviour . Statistically significant improvements for change in self-reported exercise were demonstrated ( P = 0.007 ) ; to 2—3 times per week in the intervention group compared to 0—1 times per week in the control group , and in fruit and vegetable consumption ( P = 0.033 ) ; to 10 portions of fruit and vegetables consumed per week in the intervention group compared to 1 or 2 portions a week for the control group . No evidence of a difference between groups was seen for alcohol consumption or Hospital Anxiety and Depression Scale . Conclusions : While no difference was demonstrated between the groups for readiness to change behaviour , a clinical ly significant effect in reported exercise behaviour and diet were demonstrated in the intervention group . This interesting finding indicates a dissonance between the behaviour scale and actual behaviour change , potentially indicating a lack of sensitivity of the scale to detect a change in this patient group", "Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up", "Background : Lifestyle modification is associated with a substantially decreased risk of cardiovascular events . However , the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined . We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke . Methods : We conducted an observer-blind r and omized controlled trial that enrolled 70 patients ( 48 men , mean age 63.5 years ) with acute noncardioembolic mild ischemic stroke . The patients were allocated in equal numbers to a lifestyle intervention group or a control group . We performed lifestyle interventions , which comprised exercise training , salt restriction and nutrition advice for 24 weeks . Then all patients were prospect ively followed up for occurrence of the primary endpoints , including hospitalization due to stroke recurrence and the onset of other vascular events . We also evaluated systolic blood pressure ( SBP ) at the clinic and at home , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , hemoglobin A1c ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) to compare the efficacy of the lifestyle interventions . Results : This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy . After the 24-week intervention period , the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake ( physical activity , p = 0.012 ; salt intake , p blood pressure was decreased and the HDL-C levels were increased in the intervention group ( SBP , p LDL-C , HbA1c and hs-CRP tended to decrease in the intervention group , but this decrease did not achieve significance . After a median follow-up period of 2.9 years , 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event . A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis . Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the r and omized groups ( p = 0.005 ) . Conclusions : Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke", "BACKGROUND AND PURPOSE Shared care initiatives , albeit commonly utilised in managing other chronic conditions have not been implemented in the area of stroke in Australia . The aims of this project were to adopt a shared care approach for stroke survivors comparing an experimental \" shared-care \" group with a \" treatment-as-usual \" control group in reference to the normalization or reversal of vascular risk factors and the detection and management of post-stroke depression . METHODS A r and omised controlled experimental research design was implemented with participants r and omized to an intervention or control group and followed over a 12-month period . The treatment group consisted of a r and omly selected group of patients , discharged from an acute stroke unit and transferred into the shared care model . Risk factors for stroke and depression were compared between the two groups . RESULTS Of 97 patients originally included in the study , 17 dropped out . At 12 months , 80 patients remained for analysis ( 35 in the intervention group and 45 in the control group ) . The findings demonstrated positive trends for patients within the intervention group that were not found within the control group . The percentage of intervention patients reaching target systolic blood pressure ( sBP ) of 140 mmHg after 12 months tended to be greater than in the control group ( p=0.11 , NS ) . In the intervention group , at 12 months , the total cholesterol greater than 5.18 mmol/L was 12.5 % compared to 58.8 % at discharge . In contrast this trend was not so distinct in the control group ( 57.7 % to 42.9 % ) . The percentage of patients reaching target ( recommended ) total cholesterol of 5.18 mmol/L was significantly greater in the shared care patients intervention group relative to the control group ( p=0.02 ) . The average number of walks per week was also significantly greater in intervention group compared to the control group ( p=0.048 ) . Moreover , 45 % of the control group screened as depressed compared with 20 % of the intervention group at 12 months ( p=0.06 ) . CONCLUSIONS This study demonstrates that major risk factors for recurrent stroke and vascular disease in general are better managed with the shared care model than with usual post-discharge care . The significantly reduced depression as found on the screening PHQ9 at 12 months indicated that the intervention was beneficial not only in the detection of depression but also treatment", "BACKGROUND Patients with acute stroke often have a striking lack of knowledge of causes , warning signs , and risk factors . Lack of knowledge may lead to inappropriate secondary prevention behavior . We investigated the knowledge of patients with a TIA or minor stroke about specific aspects of their disease 3 months after the event . METHODS Patients with a TIA or minor stroke who participated in a r and omized controlled trial of the effect of health education by an individualized multimedia computer program ( IMCP ) were included . All patients received information about their disease from their treating neurologist and half of the patients received extra information through the IMCP . The patients ' knowledge was tested after 3 months by means of a question naire that contained items on pathogenesis , warning signs , vascular diseases , risk factors , lifestyle and treatment . The highest possible score was 71 points . RESULTS The 57 patients had a mean total score of 41.2 points ( SD 10.4 ) of the maximum 71 . Only 15 ( 26 % ) correctly identified the brain as the affected organ in stroke and TIA , and only 21 ( 37 % ) could give a correct description of a TIA or stroke . In contrast , 80 - 90 % of the patients identified hypertension and /or obesity as vascular risk factors . Knowledge of various treatment modalities of hypertension , hypercholesterolemia and obesity was moderate to high ( 40 - 91 % adequate responses ) . CONCLUSION The vast majority of patients with TIA or stroke lack specific knowledge about their disease , but they do have a reasonable knowledge of general vascular risk factors and treatment . This suggests that counseling by neurologists of patients with a TIA or stroke can be improved", "OBJECTIVE We sought to evaluate whether comprehensive postdischarge care management for stroke survivors is superior to organized acute stroke department care with enhanced discharge planning in improving a profile of health and well-being . METHODS This was a r and omized trial of a comprehensive postdischarge care management intervention for patients with ischemic stroke and National Institutes of Health Stroke Scale scores greater than or equal to 1 discharged from an acute stroke department . An advanced practice nurse performed an in-home assessment for the intervention group from which an interdisciplinary team developed patient-specific care plans . The advanced practice nurse worked with the primary care physician and patient to implement the plan during the next 6 months . The intervention and usual care groups were compared using a global and closed hypothesis testing strategy . Outcomes fell into 5 domains : ( 1 ) neuromotor function , ( 2 ) institution time or death , ( 3 ) quality of life , ( 4 ) management of risk , and ( 5 ) stroke knowledge and lifestyle . RESULTS Treatment effect was near 0 SD for all except the stroke knowledge and lifestyle domain , which showed a significant effect of the intervention ( P = .0003 ) . CONCLUSIONS Postdischarge care management was not more effective than organized stroke department care with enhanced discharge planning in most domains in this population . The intervention did , however , fill a postdischarge knowledge gap", "The objective of this study was to conduct a r and omized , parallel-group clinical trial assessed the efficacy of a health-enhancing physical activity program ( exercise and education ) on vascular risk factors and aerobic fitness in patients who have experienced a transient ischemic attack ( TIA ) or nondisabling stroke . Sixty patients ( 69±11 years ) completed a baseline ( BL ) vascular risk stratification and aerobic fitness examination ( cycle test ) within 2 weeks of symptom onset . Subjects were then r and omized to either an 8-week , twice weekly exercise program or to a usual-care control ( CON ) group . Postintervention ( PI ) assessment s were completed immediately after the intervention and at 3-month follow-up . A series of primary ( systolic blood pressure [ SBP ] ) and secondary ( vascular risk factors like total cholesterol [ TC ] , high-density lipoproteins , etc . ; Framingham risk score ; peak oxygen uptake ) outcome measures were assessed . Significantly greater reductions in SBP ( mean change±SD ; -10.4±9.2 mm Hg ) and TC ( -.53±.90 mmol/L ) were observed between BL and PI assessment s for the exercise group compared with the CON group ( -1.9±15.4 mm Hg and -.08±.59 mmol/L , respectively ) ( P.05 ) . Significant improvements in aerobic fitness were also observed and maintained at the 3-month follow-up assessment after regular exercise participation ( P in exercise result ed in significant improvements in vascular risk factors and fitness in those diagnosed with TIA . As these beneficial effects were maintained up to 3 months after completing the exercise program , exercise should be considered a useful additive treatment strategy for newly diagnosed TIA patients . Future research should examine the long-term efficacy of such programs", "Abstract Goal : Evidence -based guidelines exist for the prevention and treatment of patients with cerebral ischemia . Despite these guidelines , there are gaps in clinical practice . Our study aim ed to determine if a physician-directed , nurse-case-management program could reduce individual patient vascular risk factors . Methods : Patients hospitalized with atherosclerotic cerebral ischemia with ≥ 1 major uncontrolled risk factor for stroke ( hypertension , tobacco use , dyslipidemia , diabetes ) were eligible to enroll in our study . Patients were r and omized to management by the nurse-prevention program or usual care . Patients in the usual-care group received their initial risk-factor assessment and a scheduled follow-up at 1 year . Patients in the usual-care group underwent further follow-up by primary care and /or neurology as recommended during their hospitalization or outpatient visit . Patients assigned to the prevention group received individualized education , motivational interviewing , and were aided in setting up their risk-factor modification goal plan . Additional education was tailored to each patient based on individualized risk factors . Prevention-group patients also underwent consultation with a registered dietitian and an exercise physiologist . The primary endpoint of the study was improvement of ≥ 1 major patient risk factor for occurrence of stroke to goal at 1 year . Results : At 1-year post-hospitalization , patients in the nurse-care-management group were 42 % more likely to have met the primary endpoint ( n = 18 ; 61 % nurse-managed patients ) compared with 33 % ( n = 18 ) of patients undergoing usual care ( P = 0.09 ) . There was no significant reduction in minor risk factors for either patient group . Patients in the prevention group had greater reductions in low-density lipoprotein cholesterol levels ( −38 vs −4 ; P = 0.0083 ) , changes in cardiovascular risk score ( −5.2 vs 1.3 ; P = 0.0033 ) , and had a greater reductions in systolic blood pressure ( −12.2 vs −0.105 ; P = 0.07 ) than their usual-care counterparts ( changes shown respectively ) . Patients in the prevention group were more likely to follow a prescribed diet than those in the usual-care group ( 50 % ) vs 7 % , respectively ; P = 0.0070 ) and maintain an exercise program ( 83 % vs 33 % , respectively ; P = 0.0018 ) . Summary : A physician-directed , nurse case-management system for patients post-hospitalization for cerebral ischemia is feasible and may help improve long-term control of major patient risk factors for stroke . A larger trial is needed to verify trends noted in our study", "BACKGROUND Our aim was to investigate whether a nurse-coordinated multidisciplinary , family-based preventive cardiology programme could improve st and ards of preventive care in routine clinical practice . METHODS In a matched , cluster-r and omised , controlled trial in eight European countries , six pairs of hospitals and six pairs of general practice s were assigned to an intervention programme ( INT ) or usual care ( UC ) for patients with coronary heart disease or those at high risk of developing cardiovascular disease . The primary endpoints-measured at 1 year-were family-based lifestyle change ; management of blood pressure , lipids , and blood glucose to target concentrations ; and prescription of cardioprotective drugs . Analysis was by intention to treat . The trial is registered as IS RCT N 71715857 . FINDINGS 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC , respectively . In patients with coronary heart disease who smoked in the month before the event , 136 ( 58 % ) in the INT and 154 ( 47 % ) in the UC groups did not smoke 1 year afterwards ( difference in change 10.4 % , 95 % CI -0.3 to 21.2 , p=0.06 ) . Reduced consumption of saturated fat ( 196 [ 55 % ] vs 168 [ 40 % ] ; 17.3 % , 6.4 to 28.2 , p=0.009 ) , and increased consumption of fruit and vegetables ( 680 [ 72 % ] vs 349 [ 35 % ] ; 37.3 % , 18.1 to 56.5 , p=0.004 ) , and oily fish ( 156 [ 17 % ] vs 81 [ 8 % ] ; 8.9 % , 0.3 to 17.5 , p=0.04 ) at 1 year were greatest in the INT group . High-risk individuals and partners showed changes only for fruit and vegetables ( p=0.005 ) . Blood-pressure target of less than 140/90 mm Hg was attained by both coronary ( 615 [ 65 % ] vs 547 [ 55 % ] ; 10.4 % , 0.6 to 20.2 , p=0.04 ) and high-risk ( 586 [ 58 % ] vs 407 [ 41 % ] ; 16.9 % , 2.0 to 31.8 , p=0.03 ) patients in the INT groups . Achievement of total cholesterol of less than 5 mmol/L did not differ between groups , but in high-risk patients the difference in change from baseline to 1 year was 12.7 % ( 2.4 to 23.0 , p=0.02 ) in favour of INT . In the hospital group , prescriptions for statins were higher in the INT group ( 810 [ 86 % ] vs 794 [ 80 % ] ; 6.0 % , -0.5 to 11.5 , p=0.04 ) . In general practice s in the intervention groups , angiotensin-converting enzyme inhibitors ( 297 [ 29 % ] INT vs 196 [ 20 % ] UC ; 8.5 % , 1.8 to 15.2 , p=0.02 ) and statins ( 381 [ 37 % ] INT vs 232 [ 22 % ] UC ; 14.6 % , 2.5 to 26.7 , p=0.03 ) were more frequently prescribed . INTERPRETATION To achieve the potential for cardiovascular prevention , we need local preventive cardiology programmes adapted to individual countries , which are accessible by all hospitals and general practice s caring for coronary and high-risk patients", "SIR— Interventions with an educational or counselling component have been reported to be effective in a variety of patient groups to encourage smoking cessation [ 1 ] , lower blood pressure ( BP ) [ 2 , 3 ] , achieve modest reductions in cholesterol [ 4 ] , and promote weight loss [ 5 ] . Evaluation of the impact of education on physical outcomes is lacking in stroke disease , despite evidence that inadequate provision of information may adversely affect compliance with secondary prevention and psychosocial outcomes [ 6 ] . We describe a single-blind r and omised controlled trial of health education and counselling for patients with stroke or transient ischaemic attack ( TIA ) , and its effects on risk factors , satisfaction , mood and perceived health status" ]	41186350-06ff-11f0-808a-c43d1ab1c353
de la Motte , SJ , Lisman , P , Gribbin , TC , Murphy , K , and Deuster , PA . Systematic review of the association between physical fitness and musculoskeletal injury risk : part 3-flexibility , power , speed , balance , and agility . J Strength Cond Res 33(6 ) : 1723 - 1735 , 2019-We performed a systematic review and evaluation of the existing scientific literature on the association between flexibility , power , speed , balance , and agility , and musculoskeletal injury ( MSK-I ) risk in military and civilian population s. MEDLINE , EBSCO , EMBASE , and the Defense Technical Information Center were search ed for original studies published from 1970 to 2015 that examined associations between these physical fitness measures ( flexibility , power , speed , balance , and agility ) and MSK-I. Method ological quality and strength of the evidence were determined after criteria adapted from previously published systematic review s. Twenty-seven of 4,229 citations met our inclusion criteria . Primary findings indicate that there is ( a ) moderate evidence that hamstring flexibility , as measured by performance on a sit- and -reach test or active straight leg raise test assessed with goniometry , and ankle flexibility , assessed with goniometry , are associated with MSK-I risk ; ( b ) moderate evidence that lower body power , as measured by performance on a st and ing broad jump or vertical jump with no countermovement , is associated with MSK-I risk ; ( c ) moderate evidence that slow sprint speed is associated with MSK-I risk ; ( d ) moderate evidence that poor performance on a single-leg balance test is associated with increased risk for ankle sprain ; and ( e ) insufficient evidence that agility is associated with MSK-I risk . Several measures of flexibility , power , speed , and balance are risk factors for training-related MSK-I in military and civilian athletic population s. Importantly , these findings can be useful for military , first responder , and athletic communities who are seeking evidence -based metrics for assessing or stratifying population s for risk of	[ "Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk ", "Background The injury risk in football is high , but little is known about causes of injury . Purpose To identify risk factors for football injuries using a multivariate model . Study Design Prospect i ve cohort study . Methods Participants were 306 male football players from the two highest divisions in Icel and . Before the 1999 football season started , the following factors were examined : height , weight , body composition , flexibility , leg extension power , jump height , peak O2 uptake , joint stability , and history of previous injury . Injuries and player exposure were recorded throughout the competitive season . Results Older players were at higher risk of injury in general ( odds ratio [ OR ] = 1.1 per year , P = 0.05 ) . For hamstring strains , the significant risk factors were age ( OR = 1.4 [ 1 year ] , P groin strains , the predictor risk factors were previous groin strains ( OR = 7.3 , P = 0.001 ) and decreased range of motion in hip abduction ( OR = 0.9 [ 1 ° ] , P = 0.05 ) . Previous injury was also identified as a risk factor for knee ( OR = 4.6 ) and ankle sprains ( OR = 5.3 ) . Conclusions Age and previous injury were identified as the main risk factors for injury among elite football players from Icel and", "This prospect i ve study was conducted to determine whether hip muscle strength and flexibility play a role in the incidence of adductor and hip flexor strains in National Hockey League ice hockey team players . Hip flexion , abduction , and adduction strength were measured in 81 players before two consecutive seasons . Thirty-four players were cut , traded , or sent to the minor league before the beginning of the season . Injury and individual exposure data were recorded for the remaining 47 players . Eight players experienced 11 adductor muscle strains , and there were 4 hip flexor strains . Preseason hip adduction strength was 18 % lower in the players who subsequently sustained an adductor muscle strain compared with that of uninjured players . Adduction strength was 95 % of abduction strength in the uninjured players but only 78 % of abduction strength in the injured players . Preseason hip adductor flexibility was not different between players who sustained adductor muscle strains and those who did not . These results indicate that preseason hip strength testing of professional ice hockey players can identify players at risk of developing adductor muscle strains . A player was 17 times more likely to sustain an adductor muscle strain if his adductor strength was less than 80 % of his abductor strength", "Background : Ankle sprains are a common and potentially disabling injury . Successful prediction of susceptibility to ankle sprain injury with a simple test could allow ankle sprain prevention protocol s to be initiated and help prevent disability in the athletic population . Objective : To investigate the ability of the single leg balance ( SLB ) test , carried out at preseason physical examination , to predict an ankle sprain during the autumn sports season . Design : Prospect i ve cohort study Setting : High school varsity athletics and intercollegiate athletics . Main outcome measure : Ankle sprains in athletes with positive SLB tests . Results : The association between a positive SLB test and future ankle sprains was significant . Controlling for confounding variables , the relative risk for an ankle sprain with a positive SLB test was 2.54 ( 95 % confidence interval , 1.02 to 6.03 ) . Athletes with a positive SLB test who did not tape their ankles had an increased likelihood of developing ankle sprains . The relative risk for ankle sprain for a positive SLB test and negative taping was 8.82 ( 1.07 to 72.70 ) . A history of previous ankle injury was not associated with future ankle sprains in this study . The κ value for interrater reliability for the SLB test was 0.898 ( p SLB test and ankle sprain . In athletes with a positive SLB test , not taping the ankle imposed an increased risk of sprain . The SLB test is a reliable and valid test for predicting ankle sprains", "Objectives : To identify risk factors for hamstring injury at the community level of Australian football . Methods : A total of 126 community level Australian football players participated in this prospect i ve cohort study . To provide baseline measurements , they completed a question naire and had a musculoskeletal screen during the 2000 preseason . All were monitored over the season . Injury surveillance and exposure data were collected for the full season . Survival analysis was used to identify independent predictors of hamstring injury . Results : A hamstring injury was the first injury of the season in 20 players ( 16 % ) . After adjustment for exposure , increasing age and decreased quadriceps flexibility were identified as significant independent predictors of the time to sustaining a hamstring injury . Older age ( ⩾23 years ) was associated with an increased risk of hamstring injury ( RR 3.8 ; 95 % confidence interval ( CI ) 1.1 to 14.0 ; p = 0.044 ) . Players with increased quadriceps flexibility ( as measured by the modified Thomas test ) were less likely to sustain a hamstring injury ( RR 0.3 ; 95 % CI 0.1 to 0.8 ; p = 0.022 ) . Conclusions : The findings of this study can be used in the development of hamstring injury prevention strategies and to identify Australian football players at increased risk of hamstring injury", "Background A one-year prospect i ve examination of injury rates and injury risk factors was conducted in Federal Bureau of Investigation ( FBI ) new agent training . Methods Injury incidents were obtained from medical records and injury compensation forms . Potential injury risk factors were acquired from a lifestyle question naire and existing data at the FBI Academy . Results A total of 426 men and 105 women participated in the project . Thirty-five percent of men and 42 % of women experienced one or more injuries during training . The injury incidence rate was 2.5 and 3.2 injuries/1,000 person-days for men and women , respectively ( risk ratio ( women/men ) = 1.3 , 95 % confidence interval = 0.9 - 1.7 ) . The activities most commonly associated with injuries ( % of total ) were defensive tactics training ( 58 % ) , physical fitness training ( 20 % ) , physical fitness testing ( 5 % ) , and firearms training ( 3 % ) . Among the men , higher injury risk was associated with older age , slower 300-meter sprint time , slower 1.5-mile run time , lower total points on the physical fitness test ( PFT ) , lower self-rated physical activity , lower frequency of aerobic exercise , a prior upper or lower limb injury , and prior foot or knee pain that limited activity . Among the women higher injury risk was associated with slower 300-meter sprint time , slower 1.5-mile run time , lower total points on the PFT , and prior back pain that limited activity . Conclusion The results of this investigation supported those of a previous retrospective investigation emphasizing that lower fitness and self-reported pain limiting activity were associated with higher injury risk among FBI new agents", "Background : Injuries in collegiate ice hockey can result in significant time lost from play . The identification of modifiable risk factors relating to a player ’s physical fitness allows the development of focused training and injury prevention programs targeted at reducing these risks . Purpose : To determine the ability of preseason fitness outcomes to predict in-season on-ice injury in male collegiate ice hockey players . Study Design : Prognostic cohort study . Level of Evidence : Level 3 . Methods : Athlete demographics , percentage body fat , aerobic capacity ( 300-m shuttle run ; 1- , 1.5- , 5-mile run ) , and strength assessment ( sit-ups , push-ups , grip strength , bench press , Olympic cleans , squats ) data were collected at the beginning of 8 successive seasons for 1 male collegiate ice hockey team . Hockey-related injury data and player-level practice /game athlete exposure ( AE ) data were also prospect ively collected . Seventy-nine players participated ( 203 player-years ) . Injury was defined as any event that result ed in the athlete being unable to participate in 1 or more practice s or games following the event . Multivariable logistic regression was performed to determine the ability of the independent variables to predict the occurrence of on-ice injury . Results : There were 132 injuries ( mean , 16.5 per year ) in 55 athletes . The overall injury rate was 4.4 injuries per 1000 AEs . Forwards suffered 68 % of the injuries . Seventy percent of injuries occurred during games with equal distribution between the 3 periods . The mean number of days lost due to injury was 7.8 ± 13.8 ( range , 1 - 127 days ) . The most common mechanism of injury was contact with another player ( 54 % ) . The odds of injury in a forward was 1.9 times ( 95 % CI , 1.1 - 3.4 ) that of a defenseman and 3 times ( 95 % CI , 1.2 - 7.7 ) that of a goal ie . The odds of injury if the player ’s body mass index ( BMI ) was ≥25 kg/m2 was 2.1 times ( 95 % CI , 1.1 - 3.8 ) that of a player with a BMI odds ratios for bench press , maximum sit-ups , and Olympic cleans were statistically significant but close to 1.0 , and therefore the clinical relevance is unknown . Conclusion : Forwards have higher odds of injury relative to other player positions . BMI was predictive of on-ice injury . Aerobic fitness and maximum strength outcomes were not strongly predictive of on-ice injury", "INTRODUCTION Increasing age is a commonly identified predictor of hamstring injury but is not modifiable to reduce injury risk . Why increasing age is a risk factor for hamstring injuries in athletes has not been studied to date . This study aim ed to identify potentially modifiable age-related changes that predict hamstring injury in a population of Australian football players . METHODS One hundred and one young ( or = 25 years ) , Australian football players , without a history of hamstring injury in the past 12 months were studied prospect ively . Players underwent screening of anthropometric , flexibility and lower extremity range of movement tests during the pre-season period and were followed-up for a full season with respect to injury and match participation . Comparisons of the age groups were performed to identify differences related to age . Logistic regression analysis was undertaken to determine whether the observed differences were predictors of hamstring injury . RESULTS There were significant differences between the age groups with respect to body weight , body mass index , hip flexor flexibility , hip internal rotation and ankle dorsiflexion range of movement . Body weight and hip flexor flexibility were significant independent predictors of hamstring injury in players aged > or = 25 years . None of the observed differences were predictors of injury in the younger age group . CONCLUSIONS There are age-related changes that are potentially modifiable to reduce injury risk in older athletes and these factors should be considered in the development of hamstring injury prevention programs for this high risk group", "Reliable data on the impact of physical training on light infantry units in terms of injuries and time loss are sparse . This study evaluated a light infantry unit ( n = 181 ) prospect ively and followed it throughout one year of infantry training and operations . Fifty-five percent of the soldiers ( n = 101 ) experienced one or more injuries . Eighty-eight percent of the injuries were training-related conditions , which result ed in 1,103 days of limited duty . Lower extremity overuse injuries were the most common type of injury documented . Fractures accounted for the greatest number of days of limited duty . Risk factors for training-related injuries identified by this study were cigarette smoking , high percentage of body fat , extremely high or low body mass index , low endurance levels , and low muscular endurance levels ( sit-ups ) . Logistic regression showed that cigarette smoking and low endurance levels were independent risk factors for training injuries . These data indicate that the incidence of training-related injuries in infantry units is high . A number of modifiable injury risk factors were identified , suggesting that many of these injuries may be preventable", "Objective To identify gender-specific predictors of lower extremity injury among a sample of adults engaging in running , walking , or jogging ( RWJ ) for exercise . Design Prospect i ve cohort study . Setting Cooper Clinic Preventive Medicine Center , Dallas , Texas . Participants Participants were 2,481 men and 609 women who underwent a physical examination between 1970 and 1981 and returned a follow-up survey in 1986 . Predictor variables measured at baseline included height , weight , and cardiorespiratory fitness . At follow-up , participants recalled information about musculoskeletal injuries , physical activity levels , and other predictors for lower extremity injury over two time periods , 5 years and 12 months . Main Outcome Measures An injury was defined as any self-reported lower extremity injury that required a consultation with a physician . Cox proportional hazards regression ( HR ) was used to predict the probability of lower extremity injury for the 5-year recall period , and unconditional logistic regression was used for the 12-month recall period . Results Among men , previous lower extremity injury was the strongest predictor of lower extremity injury ( HR = 1.93–2.09 ) , regardless of recall period . Among women , RWJ mileage > 20 miles/wk was the strongest predictor for the 5-year period ( HR = 2.08 ) , and previous lower extremity injury was the strongest predictor for the 12-month period ( HR = 2.81 ) . Conclusions For healthy adults , walking at a brisk pace for 10–20 miles per week accumulates adequate moderate-intensity physical activity to meet national recommendations while minimizing the risk for musculoskeletal lower extremity injury . Clinicians may use this information to provide appropriate injury prevention counseling to their active patients", "Knapik , JJ , Swedler , DI , Grier , TL , Hauret , KG , Bullock , SH , Williams , KW , Darakjy , SS , Lester , ME , Tobler , SK , and Jones , BH . Injury reduction effectiveness of selecting running shoes based on plantar shape . J Strength Cond Res 23(3 ) : 685 - 697 , 2009-Popular running magazines and running shoe companies suggest that imprints of the bottom of the feet ( plantar shape ) can be used as an indication of the height of the medial longitudinal foot arch and that this can be used to select individually appropriate types of running shoes . This study examined whether or not this selection technique influenced injury risk during United States Army Basic Combat Training ( BCT ) . After foot examinations , BCT recruits in an experimental group ( E : n = 1,079 men and 451 women ) selected motion control , stability , or cushioned shoes for plantar shapes judged to represent low , medium , or high foot arches , respectively . A control group ( C : n = 1,068 men and 464 women ) received a stability shoe regardless of plantar shape . Injuries during BCT were determined from outpatient medical records . Other previously known injury risk factors ( e.g. , age , fitness , and smoking ) were obtained from a question naire and existing data bases . Multivariate Cox regression controlling for other injury risk factors showed little difference in injury risk between the E and C groups among men ( risk ratio ( E/C ) = 1.01 ; 95 % confidence interval = 0.88 - 1.16 ; p = 0.87 ) or women ( risk ratio ( E/C ) = 1.07 ; 95 % confidence interval = 0.91 - 1.25 ; p = 0.44 ) . In practical application , this prospect i ve study demonstrated that selecting shoes based on plantar shape had little influence on injury risk in BCT . Thus , if the goal is injury prevention , this selection technique is not necessary in BCT", "Ankle sprains are extremely common . However , very little is known about the variables that predispose individuals to these injuries . The purpose of this study was to examine prospect ively intrinsic risk factors for inversion sprains in a young physically active female population . One hundred and fifty-nine female physical education students were evaluated for several possible intrinsic risk factors for inversion sprains at the beginning of their academic study . The evaluated intrinsic risk factors included anthropometrical and physical characteristics , ankle joint position sense , isokinetic ankle muscle strength , lower leg alignment characteristics , postural control and muscle reaction time during a sudden inversion perturbation . All sports injuries were registered during 1 - 3 years and exposure to sport was recorded ( mean : 15.33+/-4.33 h a week ) . Thirty-two ( 20 % ) of the 159 females sprained their ankle . The number of ankle sprains per 1000 h of sports exposure was 0.75 . The Cox regression analysis revealed that females with less accurate passive joint inversion position sense [ hazard ratio ( HR ) : 1.08 , 95 % confidence interval ( CI ) : 1.02 - 1.14 for absolute error at 15 degrees inversion ] , a higher extension range of motion at the first metatarsophalangeal joint ( HR : 1.03 , 95 % CI : 1.00 - 1.06 ) and less coordination of postural control ( HR : 0.96 , 95 % CI : 0.93 - 1.00 for endpoint excursion ; HR : 0.94 , 95 % CI : 0.89 - 0.99 for maximal endpoint excursion ) are at greater risk of an ankle sprain . The findings of this study suggest that effective prevention and conservative rehabilitation of ankle inversion sprains should include attention to these variables", "OBJECTIVES Well-developed physical qualities may protect against contact injuries . However , the potential contribution of physical qualities as risk or protective factors to contact injury risk is yet to be determined for rugby league . This study applied a frailty survival model that accounts for recurrent injury to identify risk factors for all physiotherapist-reported contact injury in professional rugby league players . DESIGN Prospect i ve cohort study . METHODS Sixty-six professional rugby league players participated in this three successive year prospect i ve study . At the start of each season , all players underwent measurements of st and ard anthropometry ( height , body mass , and sum of seven skinfolds ) , speed ( 10 m and 40 m sprint ) , muscular strength ( 1 repetition maximum [ RM ] bench press , 1RM squat , 1RM weighted chin-ups ) , power ( vertical jump , bench throw , 1RM power clean , jump squat ) , and endurance ( maximum repetition bench press with 60 kg resistance ) , repeated-sprint ability ( 12 × 20 m sprints performed on a 20s cycle ) , prolonged high-intensity intermittent running ability ( 8 × 12 s maximal effort shuttles performed on a 48 s cycle ) , and maximal aerobic power ( multi-stage fitness test ) . Data was used to demonstrate the application of the frailty model extension of the Cox proportional regression model for recurrent events to identify factors associated with a high hazard ratio ( HR ) of injury . RESULTS Heavier ( body mass , HR=2.6 , 95 % CI=1.2 - 5.7 ) , and faster ( 40 m sprint , HR=2.1 , 95 % CI=1.0 - 4.2 ) players , and those with poorly developed prolonged high-intensity intermittent running ability ( HR=2.9 , 95 % CI=1.7 - 5.0 ) and upper-body strength ( chin-up , HR=2.2 , 95 % CI=1.3 - 3.7 ) had a higher incidence of contact injuries . CONCLUSIONS This study demonstrates application of a novel statistical approach for the analysis of injury data that is recurrent in nature . This approach identified that the greater impact forces generated from heavier players with faster speed may result in an increase in recurrent contact injury rates . However , the development of prolonged high-intensity intermittent running ability and upper-body strength and power may assist to reduce the risk of contact injury in professional rugby league players" ]	411863c8-06ff-11f0-808a-c43d1ab1c353
CONTEXT AND OBJECTIVE Taking the outcome of mortality into consideration , there is controversy about the beneficial effects of neuraxial anesthesia for orthopedic surgery . The aim of this study was to compare the effectiveness and safety of neuraxial anesthesia versus general anesthesia for orthopedic surgery . DESIGN AND SETTING Systematic review at Universidade Federal de Alagoas . METHODS We search ed the Cochrane Central Register of Controlled Trials ( Issue 10 , 2012 ) , PubMed ( 1966 to November 2012 ) , Lilacs ( 1982 to November 2012 ) , SciELO , EMBASE ( 1974 to November 2012 ) and reference lists of the studies included . Only r and omized controlled trials were included . RESULTS Out of 5,032 titles and abstract s , 17 studies were included . There were no statistically significant differences in mortality ( risk difference , RD : -0.01 ; 95 % confidence interval , CI : -0.04 to 0.01 ; n = 1903 ) , stroke ( RD : 0.02 ; 95 % CI : -0.04 to 0.08 ; n = 259 ) , myocardial infa rct ion ( RD : -0.01 ; 95 % CI : -0.04 to 0.02 ; n = 291 ) , length of hospitalization ( mean difference , -0.05 ; 95 % CI : -0.69 to 0.58 ; n = 870 ) , postoperative cognitive dysfunction ( RD : 0.00 ; 95 % CI : -0.04 to 0.05 ; n = 479 ) or pneumonia ( odds ratio , 0.61 ; 95 % CI : 0.25 to 1.49 ; n = 167 ) . CONCLUSION So far , the evidence available from the studies included is insufficient to prove that neuraxial anesthesia is more effective and safer than general anesthesia for orthopedic surgery . However , this systematic review does not rule out clinical ly important differences with regard to mortality , stroke , myocardial infa rct ion , length of hospitalization , postoperative cognitive dysfunction or pneumonia	[ "This study compared the effects of general and regional anesthesia on cognitive and psychosocial functioning in elderly persons . Sixty-four patients between 60 and 86 yr of age undergoing knee arthroplasty were r and omly assigned to receive either general or regional anesthesia . A battery of psychometric tests , including the Satz-Mogel form of the Wechsler Adult Intelligence Scale-Revised , the Wechsler Memory Scale-Revised and the Sickness Impact Profile , and various neuropsychological measures were administered by a blinded observer just before surgery and again 3 months later . Analyses of covariance revealed improvements in most measures that were equivalent between groups . The results indicated that there were no cognitive or psychosocial effects of general or regional anesthesia after 3 months in elderly persons undergoing knee arthroplasty . In this patient population , general anesthesia poses no more risk to long-term mental function than regional anesthesia", "General or regional anesthesia may be used for lumbar laminectomy . To determine whether one method is superior , 122 patients were r and omly assigned to receive either a st and ard general anesthetic ( GA ) or spinal anesthesia ( SA ) supplemented with intravenous ( IV ) propofol sedation . Data from the intraoperative period through hospital discharge were collected and compared . Demographically , both groups were similar . Total anesthesia ( 131.0 + /- 4.3 vs 106.6 + /- 3.2 min ) and surgical times ( 81.5 + /- 3.6 vs 67.1 + /- 2.8 min ) were longer in the GA group . Intraoperative hemodynamics were similar between groups except that the incidence of increased blood pressure was more frequent with GA ( 26.2 % vs 3.3 % ) . Blood loss was less during SA ( 133 + /- 18 mL vs 221 + /- 32 mL ) . Postanesthesia care unit ( PACU ) heart rates and mean arterial pressures were higher in the GA group . Peak pain scores in the PACU were higher after GA compared with SA ( 58 + /- 4 vs 22 + /- 3 ) as were the number of patients who required analgesics . Severe nausea was more common in the GA group both in the PACU and during the 24 h after surgery . Analgesic requirements after discharge from the PACU , urinary retention , and days in the hospital did not differ between groups . This study suggests that SA may be superior to GA both intraoperatively and postoperatively for lumbar spine procedures lasting less than 2 h. ( Anesth Analg 1996;83:559 - 64", "Twenty-seven consecutive patients scheduled for total hip replacement were r and omly divided into three groups . The first group had their operations under epidural analgesia , the second whilst breathing halothane spontaneously and patients in the third group were anaesthetised using a modified neuroleptoanaesthetic ( NLA ) technique . Blood lost during the operation was measured by a colorimetric technique . Closed suction drains were used and all blood lost after the operation collected for measurement . Deliberate hypotensive techniques were not employed . The mean operative blood loss of patients who had their operations under epidural anaesthesia was significantly less than that of patients in the other two groups , being 341 - 6 + /- 59 - 1 ml ( s.e.m . ) for the epidural group , 648 - 4 + /- 58 - 3 ml ( s.e.m . ) for the halothane group and 744 + /- 98 - 9 ml ( s.e.m . ) for the NLA group . There was no significant difference in the amounts of blood collected by closed suction drainage in any of the three groups and the mean values for total overall blood loss incurred by procedure were 734 - 1 + /- 40 - 7 ml ( s.e.m . ) for the epidural group , 986 - 3 + /- 94 - 9 ml ( s.e.m . ) for the halothane group and 1168 - 4 + /- 126 ml ( s.e.m . ) for the NLA group . In this series only 3 of 10 patients ( 30 % ) who had their operation under epidural anaesthesia required transfusion with whole blood , compared with 7 of 9 ( 78 % ) in the halothane group , and 7 of 8 ( 87 - 5 % ) in the neuroleptoanalgesia group . From this series it is evident that the need for transfusion of whole blood in total hip replacement can be significantly reduced by the use of epidural analgesia", "One hundred patients presenting for surgical treatment of fractured neck of femur were allocated to receive either spinal ( SAB ) or general ( GA ) anaesthesia . Before operation , the mean PaO2 was 9.04 kPa . There was a significant decrease in PaO2 of 0.68 kPa in GA group at 1 h after operation , while blood-gas values were unchanged in SAB group . Eight patients ( 15.7 % ) in GA group and five patients ( 10.2 % ) in SAB group died within 4 weeks of surgery . The difference was not statistically significant", "BACKGROUND : Either general or regional anesthesia can be used for lumbar disk surgery . The common anesthetic technique is general anesthesia ( GA ) . The aim of this study was to compare the intra and postoperative outcomes of spinal anesthesia ( SA ) with GA in these patients . METHODS : Seventy-two patients were enrolled in the study . They were r and omized into two groups with 37 patients in GA Group and 35 ones in SA Group . The heart rate ( HR ) , mean arterial pressure ( MAP ) , blood loss , surgeons satisfaction with the operating conditions , the severity of postoperative pain based on visual analogue scale ( VAS ) and analgesic use were recorded . RESULTS : The mean blood loss was significantly less in the SA Group compared to GA Group ( p Intraoperative maximum blood pressure and heart rate changes were significantly less in SA Group ( p surgeons satisfaction was significantly more in the SA Group ( p used postoperative analgesic as well as postoperative mean VAS was significantly less in SA Group in comparison with GA group ( p SA was superior to GA in providing postoperative analgesia and decreasing blood loss while maintained better perioperative hemodynamic stability without increasing adverse side effects", "OBJECTIVE --To determine the influence of general or regional anaesthesia on long term mental function in elderly patients . DESIGN -- Prospect i ve study of patients r and omly allocated to receive general or regional anaesthesia . SETTING --The patients ' homes and a large teaching hospital in Cardiff . SUBJECTS--146 Patients aged 60 and over scheduled for elective hip or knee replacement . MAIN OUTCOME MEASURES --Scores achieved in tests of cognitive function and functional competence . RESULTS --72 Patients were allocated to receive general anaesthesia and 74 regional anaesthesia . Anaesthetic technique did not influence the duration of the operation , time to mobilisation postoperatively , requirements for analgesia after the operation , or duration of stay in hospital . Three months after the operation there was an improvement in the score for the recognition component ( 76 ms , 95 % confidence interval 9 to 144 ) and the response component ( 82 ms , 5 to 158 ) of the choice reaction time in the group receiving general anaesthesia compared with the group receiving regional anaesthesia . This was the only significant difference between the two groups in the assessment s of cognitive and functional competence . Eleven patients receiving regional anaesthesia and 12 receiving general anaesthesia reported that their memory and concentration were worse than before the operation , but this was not confirmed by testing . CONCLUSION --Cognitive and functional competence in elderly patients was not detectably impaired after either general or regional anaesthesia when attention was paid to the known perioperative influences on mental function", "Seventy-two patients were r and omized into a prospect i ve clinical trial to evaluate the effects of epidural ( EA ) versus general anesthesia ( GA ) on the incidence of thromboembolic disease ( TED ) following total knee arthroplasty ( TKA ) . Males received aspirin 650 mg po bid and females low-dose warfarin daily to maintain the prothrombin time at 15 to 16 seconds for pharmacologic prophylaxis against TED . Thirty-four patients had EA and 38 GA for their primary TKA . Contrast venography and ventilation-perfusion scanning were performed on the sixth , seventh , and eighth postoperative days , and these were interpreted in a blinded fashion . The mean age of the 45 males and 27 females was 64 years ( range , 42 - 84 years ) . There were no significant differences between the two groups with respect to hematocrit , operative time , blood loss , number of units transfused , or hospital stay . Twelve of the 34 patients ( 35 % ) receiving an EA and 10 of the 38 patients ( 26 % ) receiving GA developed TED , an overall incidence of 31 % ( p greater than 0.05 ) Fifty-three percent of the clots were located in the popliteal vein above the trifurcation or more proximal . However , the incidence of proximal vein thrombosis was significantly less in patients receiving an EA ( 46 % ) rather than a GA ( 64 % ) . The incidence and distribution of clots was not affected by the type of pharmacologic prophylaxis , gender , or use of methylmethacrylate . Ten percent of the patients had a positive scan by strict criteria and were thought to have a pulmonary embolism ( PE ) . In patients with a femoral vein clot , the incidence of PE was 67 % . One bleeding complication occurred in a patient who took double the appropriate warfarin dose . ( ABSTRACT TRUNCATED AT 250 WORDS", "To compare the effects of epidural anesthesia and general anesthesia on early postoperative outcomes after unilateral primary total knee replacement , 262 patients were r and omly assigned to receive either epidural or general anesthesia . All patients received a common rehabilitation protocol including a st and ardized assessment of progress . One hundred eighty-eight patients received a common thromboembolic prophylaxis protocol with postoperative aspirin , and had a st and ardized surveillance protocol to detect thromboembolic complications . Deep vein thrombosis was determined by venography on the operative limb , and pulmonary embolism was determined by comparison of preoperative and postoperative lung perfusion scans . The epidural anesthesia group reached all rehabilitative milestones earlier postoperatively than did the general anesthesia group , with a statistically significant earlier attainment of stair climbing . The incidence of deep vein thrombosis was 40 % with epidural anesthesia , and 48 % with general anesthesia . There were no clots proximal to the popliteal veins . The incidence of pulmonary embolism on lung scan was 12 % with epidural anesthesia and 9 % with general anesthesia . Epidural anesthesia is associated with more rapid achievement of postoperative in hospital rehabilitation goals after total knee replacement . A minor reduction in postoperative deep vein thrombosis rate was observed with epidural anesthesia , but this did not reach statistical significance . No difference in early postoperative pulmonary embolism was observed between the 2 types of anesthesia", "Forty elderly patients ( mean age 78.9 years ) undergoing acute surgery for hip fracture were given at r and om either spinal analgesia with bupivacaine 0.75 % or general anaesthesia with diazepam , fentanly and N2O/O2 . Mental function was studied pre‐operatively with an abbreviated mental test and 1 week and 3 months postoperatively in both groups . Mortality and number of complications was similar in the two groups , but a shorter time of ambulation was seen in the spinal group compared to the general anaesthetic group . No persistent impairment in mental function was found after acute hip surgery under spinal or general anaesthesia and the only advantage of regional technique was a shorter time of ambulation", "OBJECTIVE To compare postoperative outcomes in patients having primary total knee arthroplasty receiving general or regional anaesthesia . DESIGN R and omised prospect i ve study . SETTING Regional hospital , Hong Kong . PATIENTS Patients having primary total knee replacement were r and omised to either general anaesthesia followed by postoperative intravenous patient-controlled analgesia with morphine , or combined spinal-epidural anaesthesia followed by postoperative epidural infusion of bupivacaine 0.1 % with fentanyl 2 microg/mL. MAIN OUTCOME MEASURES Visual analogue scale pain scores , perioperative blood loss , time to first meal and ambulation , and prevalence of postoperative complications . RESULTS Sixty consecutive patients were enrolled in this study . Postoperative median pain scores were consistently lower at 1 ( P regional anaesthesia . Although there was a trend towards fewer complications in the latter group , there were no statistically significant differences between the two groups with respect to the incidence of postoperative blood loss , haemodynamic instability , pruritus , nausea , vomiting , urinary retention , or other surgical/medical complications . Postoperatively , patients given regional anaesthesia also resumed meals earlier ( P earlier ambulation and hospital discharge . CONCLUSION Chinese patients undergoing total knee arthroplasty with regional anaesthesia/regionally delivered analgesia enjoyed better postoperative pain relief and resumed meals earlier than those receiving general anaesthesia/intravenous patient-controlled analgesia . The former also showed trends towards less adverse effects , postoperative complications , earlier ambulation , and earlier hospital discharge", "Amputation of the lower limb for vascular disease has a high morbidity and mortality . A comparative study in 60 patients was carried out between spinal analgesia with sedation and general anaesthesia with controlled ventilation which maintained end expiratory carbon dioxide between 4–4.5 kPa . The spinal technique had advantages over general anaesthesia during surgery and in the first 24 hours , but no long term benefits", "Background and objective : This prospect i ve , r and omized study was conducted to compare unilateral spinal block using small doses of hyperbaric bupivacaine and single-agent anaesthesia with sevoflurane in elderly patients undergoing hip surgery . Methods : Thirty patients ( > 65 yr ) undergoing hip fracture repair were r and omly allocated to receive unilateral spinal anaesthesia with hyperbaric bupivacaine 7.5 mg 0.5 % ( Group Spinal , n = 15 ) or volatile induction and maintenance anaesthesia with sevoflurane ( Group SEVO , n = 15 ) . General anaesthesia was induced by increasing the inspired concentration to 5 % . A laryngeal mask airway was placed without muscle relaxants , and the end-tidal concentrations of sevoflurane were adjusted to maintain cardiovascular stability . Hypotension ( decrease in systolic arterial pressure > 20 % from baseline ) , hypertension or bradycardia ( heart rate ) requiring treatment , and the length of stay in the postanaesthesia care unit was recorded . Cognitive functions were evaluated the previous day , and 1 and 7 days after surgery with the Mini Mental State Examination test . Results : Hypotension occurred in seven patients of Group Spinal ( 46 % ) and in 12 patients of Group SEVO ( 80 % ) ( P = 0.05 ) . Phenylephrine was required to control hypotension in three spinal patients ( 21 % ) and four SEVO patients ( 26 % ) ( n.s . ) . SEVO patients had lower heart rates than spinal patients from 15 to 60 min after anaesthesia induction ( P = 0.01 ) . Bradycardia was observed in three SEVO patients ( 22 % ) . Discharge from the postanaesthesia care unit required 15 ( range 5 - 30 ) min in Group Spinal and 55 ( 15 - 80 ) min in Group SEVO ( P = 0.0005 ) . Eight patients in Group Spinal ( 53 % ) and nine patients in Group SEVO ( 60 % ) showed cognitive decline ( Mini Mental State Examination test decreased ⩾ 2 points from baseline ) 24 h after surgery ( n.s . ) . Seven days after surgery , confusion was still present in one patient of Group Spinal ( 6 % ) and in three patients of Group SEVO ( 20 % ) ( n.s . ) . Conclusions : In elderly patients undergoing hemiarthroplasty of the hip , induction and maintenance with sevoflurane provide a rapid emergence from anaesthesia without more depression of postoperative cognitive function compared with unilateral spinal anaesthesia . This technique represents an attractive option when patient refusal , lack of adequate co-operation or concomitant anticoagulant therapy contraindicate the use of spinal anaesthesia", "The mortality following surgical correction of upper femoral fractures was investigated in 578 patients , over the age of 50 yr , r and omly allocated to receive spinal ( bupivacaine ) or general ( enflurane or neurolept ) anaesthesia . Thirty days after surgery the mortality was 6 % after spinal and 8 % after general anaesthesia ( ns ) . Six months to 2 years after surgery the mortality was identical in the two groups . There were no differences with respect to ambulation and discharge . The estimated blood loss was smaller ( P less than 0.05 ) in patients receiving spinal anaesthesia . Regardless of the anaesthetic technique , a high short-term mortality was related to age , male sex , and trochanteric fracture , whereas excess long-term mortality was related to male sex and high ASA scores", "BACKGROUND Aim of this study is to determine if and how the anaesthesia technique can significantly influence the outcome in patients after major orthopaedic surgery in terms of : patrimony of red blood cells ( blood loss and erythropoiesis ) , incidence of intra and postoperative complications , postoperative pain control and hospital stay . METHODS 210 patients , ASA physical status I-III , undergoing elective primary total hip replacement were r and omly allocated in three groups of 70 patients to receive either epidural anaesthesia ( Group EA ) , general anaesthesia ( GA ) , or epidural anaesthesia integrated with mild general anaesthesia ( IA ) . RESULTS Data show a significant difference between the amount of pain measured by VRS immediately after surgery : prevalently absent in groups IA ( 84.3 % ) and EA ( 85.7 % ) and prevalently severe and moderate in group AG ( 34.3 % ) . The measurement of the basic circulating erythrocyte mass in the first , third and fifth postoperative day , calculated by the Mercuriali formula , which considers blood loss , autologous and homologous transfusions and erythropoiesis , showed that general anaesthesia leads to a significant delay in the resumption of haemopoiesis . This result was attenuated by its combination with epidural anaesthesia . CONCLUSIONS On the basis of the literature and the results of our study , epidural anaesthesia seems to be the most appropriate technique for patients scheduled for total hip replacement : due to its simpler analgesic cover , its tendency to be associated with a lower incidence of complications in the first 24 hours after surgery . The incidence of relevant hypotension is minor compared to integrated anaesthesia . General anaesthesia produced a significant decrease in postoperative erythropoiesis", "OBJECTIVE To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults . DESIGN R and omized controlled clinical trial . SETTING Orthopedic specialty academic hospital . PATIENTS A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years ; 70 % women . INTERVENTION R and om assignment to either epidural or general anesthesia . MAIN OUTCOME MEASURES A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively . Cognitive outcome was assessed by within-patient change on 10 tests of memory , psychomotor , and language skills . Prospect i ve st and ardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes . RESULTS The two groups were similar at baseline in terms of age , sex , comorbidity , and cognitive function . There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months . Overall , 5 % of patients showed a long-term clinical ly significant deterioration in cognitive function . There was no difference between the anesthesia groups in the incidence of major cardiovascular complications ( 3 % overall ) . CONCLUSIONS The type of anesthesia , general or epidural , does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement . This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date , with more than 99 % power to detect a clinical ly significant difference on any of the neuropsychological tests", "One thous and , three hundred and thirty three patients who underwent anaesthesia for surgical fixation of a hip fracture were studied prospect ively to assess the effects on outcome of general and spinal anaesthesia . There were no significant differences between the groups in risk factors , length of hospital stay or mortality rates after 30 days or one year . The data presented may be useful for those wishing to audit anaesthetic services provided to patients with hip fracture", "The postoperative course of mental performance during the first week and at 3 months after operation was studied in 30 patients above the age of 60 , undergoing total hip replacement arthroplasty . The patients were r and omly allocated to receive either general anesthesia , epidural analgesia , or general anesthesia plus epidural analgesia . The surgically induced increase in plasma cortisol and glucose was inhibited in the two groups receiving epidural analgesia . Mental performance was studied with psychological methods . An equal degree of postoperative impairment of mental performance of 3 - 4 days ' duration was found in all groups . Three months after surgery , mental function had improved slightly and to the same extent in all groups . We conclude that the after surgery , mental function had improved slightly and to the same extent in all groups . We conclude that the transient mental impairment occurring within the first postoperative week is caused by factors other than general anesthetic agents and the endocrine-metabolic response to surgery", "Sixty patients with fractured neck of femur and scheduled for surgical correction were r and omly allocated to receive one of three anaesthetic techniques : general anaesthesia ; spinal analgesia ; psoas compartment block . The patients in the local anaesthetic groups also received a light general anaesthetic . There was little difference in the pre‐ , intra‐ and postoperative events , and no difference in postoperative mortality", "In a prospect i ve r and omized multi-centre study , the mortality following internal fixation surgery for fracture of the upper femur was investigated in 538 elderly patients allocated to receive subarachnoid blockade or general ( narcotic-relaxant ) anaesthesia . The 28-day mortality was 6.6 % with subarachnoid , and 5.9 % with general , anaesthesia . The difference was not significant ( 95 % confidence limits : -3.5 to + 4.8 ) . At 1 year following surgery , the mortality was 20.4 % . Increasing age , ischaemic heart disease , cardiac failure , preoperative arrhythmias and poor ASA status were all associated with increases in early and long term mortality . A delay to surgery of more than 24 h from admission was also associated with an increased 28-day mortality . Senile dementia and admission other than from the patient 's own home , were factors associated with a poorer long term outcome . From the point of view of mortality , subarachnoid anaesthesia did not appear to confer any advantages over general anaesthesia in non-prosthetic surgery for hip fracture in the elderly", " Fifty-seven patients , all over the age of 64 , with femoral neck fracture were r and omized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion . All patients were lucid on admission . Using the American Psychiatric Association 's Diagnostic and Statistical Manual of Mental Disorders ( DSM-III ) as criteria for confusion , we found that 44 % of the patients developed confusion that correlated closely to a history of mental depression ( P incidence of confusion between the two anesthetic groups . In patients given halothane , however , early postoperative hypoxemia was associated with confusion ( P postoperative complications and almost four times longer hospitalization times . It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique", "STUDY OBJECTIVES To determine whether lumbar epidural anesthesia , when combined with general anesthesia , decreases perioperative blood loss , the incidence of postoperative deep vein thrombosis ( DVT ) , cardiac dysrhythmias , and ischemia in patients undergoing total hip arthroplasty ( THA ) . DESIGN R and omized , controlled study . SETTING A university hospital . PATIENTS 37 ASA physical status I , II , and III patients , undergoing elective THA . INTERVENTION Patients were divided into two statistically comparable groups : Group GA = general anesthesia ; Group CEGA = general anesthesia plus lumbar epidural anesthesia . All patients had 48-hour perioperative Holter monitoring , applied on admission , the day prior to surgery . In both groups , general anesthesia was induced with thiopental sodium and muscle relaxant , and maintained with oxygen , nitrous oxide , isoflurane , opioid , and muscle relaxant . Group B received lumbar epidural anesthesia with 10 ml 0.5 % bupivacaine with 1:200,000 epinephrine prior to anesthesia induction . Blood loss was measured by suction bottle contents , sponge weights , and collection drainage . DVT was assessed with postoperative leg scanning , plethysmography , and venogram . MEASUREMENTS AND MAIN RESULTS Intraoperative blood loss was less after combined epidural-general anesthesia ( 663.8 ml + /- 299.0 ml ) than after general anesthesia alone ( 1,259.2 ml + /- 366.0 ml ) . The difference was found to be statistically significant ( p postoperative blood loss , incidence of DVT , cardiac dysrhythmias , or ischemia . CONCLUSION Combined regional-general anesthesia decreases intraoperative blood loss in THA , and thereby offers an advantage over general anesthesia alone", "Total hip or knee replacement surgeries are common orthopedic interventions that can be performed with spinal anesthesia ( SA ) or general anesthesia ( GA ) . No study has investigated the economic aspects associated with the two anesthetic techniques for this common surgery . We r and omized 40 patients to receive either SA or GA and analyzed the drug and supply costs for anesthesia und recovery . Anesthesia-related times , hemodynamic variables , and pain scores were also recorded . Total costs per case without personnel costs were almost half in the SA group compared with the GA group ; this was a result of less cost for anesthesia ( P anesthesia-related times . Patients in the GA group were admitted to the postanesthesia care unit with a higher pain score and needed more analgesics than patients in the SA group ( both P SA is a more cost-effective alternative to GA in patients undergoing hip or knee replacement , as it is associated with lower fixed and variable costs . Moreover , SA seems to be more effective , as patients in the SA group showed lower postoperative pain scores during their stay in the postanesthesia care unit", "Quantitative assessment of myocardial ischaemia during incremental spinal , single-dose spinal and general anaesthesia may provide guidelines for the choice of anaesthetic technique for osteo synthesis of hip fractures in the elderly atherosclerotic individual . Forty-three patients with coronary artery disease were allocated to receive either incremental spinal anaesthesia ( bupivacaine 0.5 % plain ) ( A ) , single-dose spinal anaesthesia ( 2.5 mL of bupivacaine 0.5 % plain ) ( B ) or general anaesthesia ( fentanyl , thiopentone , atracurium , enflurane , N2O/O2 ) ( C ) for hip surgery . ST segment monitoring was performed from the induction of anaesthesia and for the following 48 h , and perioperative hypotension , blood loss and fluid therapy were recorded . ST depression developed in two out of 14 ( A ) , seven out of 15 ( B ) and six out of 14 ( C ) patients ( P = 0.14 ) . In ( A ) , a total of seven ST depressions occurred in the observation period as opposed to 125 in ( B ) and 16 in ( C ) ( P ST depression only occurred in ( B ) . Three ( A ) , 33 ( B ) and 40 ( C ) hypotensive events were recorded ( P ST depression compared with 10 % of normotensive patients ( P bupivacaine were used as opposed to the fixed 2.5 mL dose in ( B ) ( P mortality was higher in ( B ) ( P mortality between the three groups . The incidence of hypotension and myocardial ischaemia was lowest in the group receiving incremental spinal anaesthesia" ]	411864fe-06ff-11f0-808a-c43d1ab1c353
This systematic review synthesizes evidence on the impact of conditional and unconditional cash transfers ( CCT and UCT ) on contraception in low- and middle-income countries . Scientific and gray literature data bases were search ed from 1994 to 2016 and 11 papers from ten studies were included . Most of the studies had low risk of bias . Cash transfers were used for increasing school attendance or improving health and nutrition , but not directly for contraception . Three studies showed positive impact on contraceptive use and four showed a decrease in fertility outcomes . An increase in childbearing was observed in two studies , and three studies demonstrated no impact on fertility indicators . All studies treated contraceptive use or fertility only as unintended and indirect outcomes . The available evidence on impact of CCT and UCT on contraception is inconclusive due to the limited number of studies , varying outcome measures , and lack of intervention specifically for contraception	[ "Recent evidence suggests that conditional cash transfer programs for schooling are effective in raising school enrollment and attendance . However , there is also reason to believe that such programs can affect other outcomes , such as the sexual behavior of their young beneficiaries . Zomba Cash Transfer Program is a r and omized , ongoing conditional cash transfer intervention targeting young women in Malawi that provides incentives ( in the form of school fees and cash transfers ) to current schoolgirls and recent dropouts to stay in or return to school . An average offer of US$ 10/month conditional on satisfactory school attendance – plus direct payment of secondary school fees – led to significant declines in early marriage , teenage pregnancy , and self-reported sexual activity among program beneficiaries after just one year of program implementation . For program beneficiaries who were out of school at baseline , the probability of getting married and becoming pregnant declined by more than 40 percent and 30 percent , respectively . In addition , the incidence of the onset of sexual activity was 38 percent lower among all program beneficiaries than the control group . Overall , these results suggest that conditional cash transfer programs not only serve as useful tools for improving school attendance , but may also reduce sexual activity , teen pregnancy , and early marriage", "There is promising evidence that poverty-targeted cash transfer programs can have positive impacts on adolescent transitions to adulthood in re source poor setting s , however existing research is typically from small scale programs in diverse geographic and cultural setting s. We provide estimates of the impact of a national unconditional cash transfer program , the Kenya Cash Transfer for Orphans and Vulnerable Children , on pregnancy and early marriage among females aged 12 to 24 , four years after program initiation . The evaluation was design ed as a clustered r and omized controlled trial and ran from 2007 to 2011 , capitalizing on the existence of a control group , which was delayed entry to the program due to budget constraints . Findings indicate that , among 1549 females included in the study , while the program reduced the likelihood of pregnancy by five percentage points , there was no significant impact on likelihood of early marriage . Program impacts on pregnancy appear to work through increasing the enrollment of young women in school , financial stability of the household and delayed age at first sex . The Kenyan program is similar in design to most other major national cash transfer programs in Eastern and Southern Africa , suggesting a degree of generalizability of the results reported here . Although the objective of the program is primarily poverty alleviation , it appears to have an important impact on facilitating the successful transition of adolescent girls into adulthood", "Do Conditional Cash Transfers Improve Child Health ? Evidence from PROGRESA 's Control R and omized Experiment Author(s ) : Paul Gertler Source : The American Economic Review , Vol . 94 , No. 2 , Papers and Proceedings of the One Hundred Sixteenth Annual Meeting of the American Economic Association San Diego , CA , January 3 - 5 , 2004 ( May , 2004 ) , pp . 336 - 341 Published by : American Economic Association Stable URL : http://www.jstor.org/stable/3592906 . Accessed : 13/03/2014", "Among policymakers , a common perception surrounding the effects of cash transfer programmes , particularly unconditional programmes targeted to families with children , is that they induce increased fertility . We evaluate the Zambian Child Grant Programme , a government unconditional cash transfer targeted to families with a child under the age of 5 and examine impacts on fertility and household composition . The evaluation was a cluster r and omized control trial , with data collected over 4 years from 2010 to 2014 . Our results indicate that there are no programme impacts on overall fertility . Our results contribute to a small evidence base demonstrating that there are no unintended incentives related to fertility due to cash transfers" ]	41186594-06ff-11f0-808a-c43d1ab1c353
The positive relationship between per capita availability of dairy products and average height found in historical studies ( for instance in nineteenth century Bavaria , Prussia and France ; Baten , 2009 ) does not necessarily indicate a causal relationship . Historical studies usually apply non-experimental methods that may produce substantial bias . Modern experimental controlled studies may provide high quality evidence supporting a causal relationship between consumption of dairy products and physical growth . This paper provides a systematic review and meta- analysis of controlled trials investigating the effect of supplementing usual diet with dairy products on physical growth . Twelve studies provided sufficient , independent data for meta- analysis . Seven studies were conducted since the 1990s . The other studies were conducted between 1926 and 1980 . Studies were conducted in Europe , USA , China , Northern Vietnam , Kenya , Indonesia and India . Many studies had some internal validity problems such as lack of r and omisation or dissimilarity of groups at baseline regarding height and age , which affects the quality of evidence . Meta- analysis and sensitivity analysis showed that the most likely effect of dairy products supplementation is 0.4 cm per annum additional growth per ca 245 ml of milk daily . Meta-regression analysis indicated that milk might have more effect on growth than other dairy products while lower height-for-age and being a teenager increased the effect of supplementation . In conclusion , there is moderate quality evidence that dairy products supplementation stimulate linear growth supporting hypotheses that changing levels of consumption of dairy products in the 19th and 20th centuries contributed to trends in height	[ "Background : Because of its nutrients and anabolic hormones , cow 's milk may promote height growth , which in turn has been related to breast cancer risk . We prospect ively investigated associations between dairy intakes and height growth . Methods : A cohort of 5,101 girls from throughout the United States completed annual surveys ( 1996 - 2001 , 2003 ) , providing height , weight , and past-year diet . At baseline , all were premenarchal , ages 9 years and above , with no serious medical conditions . We studied three outcomes : annual height growth , peak growth velocity , and adult height . Multivariate models estimated the effects of milk , cheese , yogurt , and energy on subsequent growth , adjusted for race/ethnicity , age , prior height , and body mass index . Other models studied fats and proteins . Results : Premenarchal girls who drank > 3 servings per day of milk grew 0.11 in . ( P = 0.02 ) more the following year than girls consuming Yogurt ( + 0.13 in./cup ; P = 0.02 ) , but not cheese or total calories , predicted height growth . In a separate model , dairy protein ( + 0.034 in./10 g ; P height growth . Larger peak velocities were seen among girls reporting , at baseline , more milk ( > 3 glasses per day versus dairy protein ( + 0.039 in./10 g ; P = 0.003 ) . Baseline milk and dairy protein predicted taller adults . Dairy protein was more important than dairy fat , for all outcomes . Nondairy animal protein and vegetable protein were never significant , nor were nondairy animal fat and vegetable fat . Conclusion : Of the foods/nutrients studied , dairy protein had the strongest association with height growth . These findings suggest that a factor in the nonlipid phase of milk , but not protein itself , has growth-promoting action in girls . ( Cancer Epidemiol Biomarkers Prev 2009;18(6):1881–7", "A r and omised controlled study was carried out of the effect on growth of the provision of free milk supplements to schoolchildren aged 7 and 8 . In selecting children for this study , the aim was to identify those whose socioeconomic circumstances might place them at a disadvantage for growth . Five hundred and eighty-one-children were selected from schools where a high proportion of the pupils received free school meals , and from families with four or more children . The subjects were r and omly allocated to receive a third of a pint ( 190 ml ) of free milk daily for six school terms or to a control group . The mean difference in height gain at the end of twenty-one- and -a-half months was 3 % or 2.93 mm ( P less than 0.05 ) in favour of the children provided with free milk . The mean difference in weight gain was 130 g ( P greater than 0.05 ) in their favour . The height and weight gain associated with the provision of free mild was very small in the study population , and it is therefore likely that the benefit to growth of providing free milk for the whole unselected population of schoolchildren of these ages would be even smaller", "Observational studies of dietary patterns and growth and studies with milk supplementation have shown that children consuming diets containing animal source foods grow better . This study evaluates the growth of 544 Kenyan schoolchildren ( median age 7.1 y ) after 23 mo of food supplementation with a meat , milk or energy supplement ( approximately 1255 kJ ) compared to a control group without a supplement . Multivariate analyses controlled for covariates compared gain in weight , height , weight-for-height Z-score ( WHZ ) , height-for-age Z-score ( HAZ ) , mid-upper-arm circumference , triceps and subscapular skinfolds , mid-upper-arm muscle and mid-upper-arm fat area . Children in each of the supplementation groups gained approximately 0.4 kg ( 10 % ) more weight than children in the Control group . Children in the Meat , Milk and Energy groups gained 0.33 , 0.19 and 0.27 cm more , respectively , in mid-upper-arm circumference than children in the Control group . Children who received the Meat supplement gained 30 - 80 % more mid-upper-arm muscle area than children in the other groups , and children who received the milk supplement gained 40 % more mid-upper-arm muscle area than children who did not receive a supplement . No statistically significant overall effects of supplementation were found on height , HAZ , WHZ or measures of body fat . A positive effect of the milk supplement on height gain could be seen in the subgroup of children with a lower baseline HAZ ( weight gain in the study children and that the addition of meat increased their lean body mass", "A 2-year milk intervention trial was carried out with 757 girls , aged 10 years , from nine primary schools in Beijing ( April 1999 - March 2001 ) . Schools were r and omised into three groups : group 1 , 238 girls consumed a carton of 330 ml milk fortified with Ca on school days over the study period ; group 2 , 260 girls received the same quantity of milk additionally fortified with 5 or 8 microg cholecalciferol ; group 3 , 259 control girls . Anthropometric and bone mineralisation measurements , as well as dietary , health and physical-activity data , were collected at baseline and after 12 and 24 months of the trial . Over the 2-year period the consumption of this milk , with or without added cholecalciferol , led to significant increases in the changes in height ( > or = 0.6 % ) , sitting height ( > or = 0.8 % ) , body weight ( > or 2.9 % ) , and ( size-adjusted ) total-body bone mineral content ( > or = 1.2 % ) and bone mineral density ( > or = 3.2 % ) . Those subjects receiving additional cholecalciferol compared with those receiving the milk without added 25-hydoxycholecalciferol had significantly greater increases in the change in ( size-adjusted ) total-body bone mineral content ( 2.4 v. 1.2 % ) and bone mineral density ( 5.5 v. 3.2 % ) . The milk fortified with cholecalciferol significantly improved vitamin D status at the end of the trial compared with the milk alone or control groups . It is concluded that an increase in milk consumption , e.g. by means of school milk programmes , would improve bone growth during adolescence , particularly when Ca intake and vitamin D status are low", "Abstract Objectives : To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls . Design : 18 month , open r and omised intervention trial . Subjects : 82 white girls aged 12.2 ( SD 0.3 ) years , recruited from four secondary schools in Sheffield . Intervention : 568 ml ( one pint ) of whole or reduced fat milk per day for 18 months . Main outcome measures : Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry . Outcome measures to evaluate mechanism included biochemical markers of bone turnover ( osteocalcin , bone alkaline phosphatase , deoxypyridinoline , N-telopeptide of type I collagen ) , and hormones important to skeletal growth ( parathyroid hormone , oestradiol , insulin-like growth factor I ) . Results : 80 subjects completed the trial . Daily milk intake at baseline averaged 150 ml in both groups . The intervention group consumed , on average , an additional 300 ml a day throughout the trial . Compared with the control group , the intervention group had greater increases of bone mineral density ( 9.6 % v 8.5 % , P=0.017 ; repeated measures analysis of variance ) and bone mineral content ( 27.0 % v 24.1 % , P=0.009 ) . No significant differences in increments in height , weight , lean body mass , and fat mass were observed between the groups . Bone turnover was not affected by milk supplementation . Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group ( 35 % v 25 % , P=0.02 ) . Conclusion : Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass . Key messages Osteoporosis is a major public health problem ; 40 % of women will sustain an osteoporotic fracture Maximising peak bone mass at skeletal maturity may be one of the most important protective measures against fracture in later life Adolescence is a critical time for bone mineral acquisition An increase in milk consumption among adolescent girls result ed in significant gains in bone mineral over an 18 month period This simple intervention indicates that increased milk consumption may be associated with higher peak bone", "OBJECTIVE To study the effect of calcium supplementation with dairy products on the bone and body composition of pubertal girls . DESIGN R and omized control study with 12-month follow-up . SETTING General community . SUBJECTS Forty-eight white girls whose mean age was 11 years and sexual development at Tanner stage 2 . INTERVENTION One group 's diet was supplemented with dairy products to the recommended dietary allowance of 1200 mg calcium daily . The other group ate their usual diet . MAIN OUTCOME MEASURES Bone mineral content and density were measured at the radius , femoral neck , lumbar spine , and total body bone mineral by single-photon and dual-energy x-ray absorptiometry at the start of the study and after 3 , 6 , 9 , and 12 months . Body composition ( lean body mass and body fat ) was measured by dual-energy x-ray absorptiometry at the same intervals . Serum calcium , phosphate , 25-hydroxyvitamin D , 1,25-dihydroxyvitamin D , alkaline phosphatase , magnesium , and albumin concentrations were determined at the start and end of the study . The urinary calcium/creatinine ratio and hydroxyproline concentration were also determined . RESULTS The dairy group had higher intakes of calcium , phosphate , vitamin D , and protein than control subjects . The dairy group had significantly greater increases during the 1-year study in bone mineral density at the lumbar spine bones ( 22.8 % + /- 6.9 % vs 12.9 % + /- 8.3 % ) and in total body bone mineral ( 14.2 % + /- 7.0 % vs 7.6 % + /- 6.0 % ) than control subjects . Dietary calcium , phosphate , vitamin D , and protein intakes were associated with the lumbar bone density and total body bone calcium . There were no differences in serum or urinary biochemical values between the two groups at the start or end of the study . CONCLUSIONS Young girls whose dietary calcium intake was provided primarily by dairy products at or above the recommended dietary allowances had an increased rate of bone mineralization . Increased intake of dairy foods did not increase overall total or saturated fat intake and was not associated with excessive weight gain or increased body fat", "Summary Background Bone mineral density ( BMD ) is largely genetically determined and this influence is most powerful in the period of rapid skeletal development in childhood and late adolescence but environmental factors such as exercise and dietary calcium intake may influence up to 20 % . Aims of the study The aims of the study were to examine healthy late adolescent females for the effects and benefits of a high calcium intake from dairy product foods on bone mineral density , body composition , lipids and biochemistry . The secondary aim is determine whether a high intake of dairy product foods in the diet is acceptable for this age group long term . Methods Ninety-one teenage girls who participated in a two-year r and omised controlled study on the effect of dairy food supplementation on dietary patterns , body composition and bone density in post-pubertal teenage girls were approached one year after the cessation of the study to determine the effects of the cessation of dairy supplements on bone mineral density , dietary habits , biochemical markers , body composition and blood lipids . Bone mineral density and bone mineral content were assessed at the hip , spine and total body . Anthropometric data were collected , and exercise , Tanner , dietary assessment , preference and compliance question naires were administered . Lipid profiles , hydroxyproline excretion and urinary calcium and sodium excretion measurements were performed . Results There were no significant differences between the 2 groups for height , weight , lean and fat mass . The supplemented group had significantly higher calcium , phosphorus and protein intake during the supplementation period ( p exercise level , preference or acceptability of dairy products or in the lipids and bone markers between baseline the end of supplementation and 1 year follow-up . There was a significant increase in trochanter ( 4.6 % ) , lumbar spine ( 1.5 % ) and femoral neck ( 4.8 % ) BMD ( p in bone mineral content at the trochanter ( p lumbar spine ; however the latter was not statistically significant , in the high calcium group at the end of supplementation . There was no difference in vertebral height or width at any stage of the study , indicating no influence on bone size . Conclusions In this 3 year study ( 2 years of supplementation , 1 year follow-up ) , teenage girls , aged 15–18 years , were able to significantly increase their BMD at the trochanter , femoral neck and lumbar spine when supplemented with dairy product foods to a mean calcium intake of 1160 mg/d . There was also an effect seen on the BMC particularly at the trochanter and to a lesser extent at the lumbar spine . The dietary calcium intake achieved did not adversely affect body weight , fat and lean mass or blood lipid profiles . Twelve months after the supplementation finished the girls had returned to their baseline diet , indicating self- selection of a high dairy product diet may be hard to achieve" ]	41186c6a-06ff-11f0-808a-c43d1ab1c353
Background : In an apparent paradox , morbidity and mortality are lower in obese patients undergoing cardiac surgery , although the nature of this association is unclear . We sought to determine whether the obesity paradox observed in cardiac surgery is attributable to reverse epidemiology , bias , or confounding . Methods : Data from the National Adult Cardiac Surgery registry for all cardiac surgical procedures performed between April 2002 and March 2013 were extracted . A parallel systematic review and meta- analysis ( MEDLINE , Embase , SCOPUS , Cochrane Library ) through June 2015 were also accomplished . Exposure of interest was body mass index categorized into 6 groups according to the World Health Organization classification . Results : A total of 401 227 adult patients in the cohort study and 557 720 patients in the systematic review were included . A U-shaped association between mortality and body mass index classes was observed in both studies , with lower mortality in overweight ( adjusted odds ratio , 0.79 ; 95 % confidence interval , 0.76–0.83 ) and obese class I and II ( odds ratio , 0.81 ; 95 % confidence interval , 0.76–0.86 ; and odds ratio , 0.83 ; 95 % confidence interval , 0.74–0.94 ) patients relative to normal-weight patients and increased mortality in underweight individuals ( odds ratio , 1.51 ; 95 % confidence interval , 1.41–1.62 ) . In the cohort study , a U-shaped relationship was observed for stroke and low cardiac output syndrome but not for renal replacement therapy or deep sternal wound infection . Counter to the reverse epidemiology hypotheses , the protective effects of obesity were less in patients with severe chronic renal , lung , or cardiac disease and greater in older patients and in those with complications of obesity , including the metabolic syndrome and atherosclerosis . Adjustments for important confounders did not alter our results . Conclusions : Obesity is associated with lower risks after cardiac surgery , with consistent effects noted in multiple analyses attempting to address residual confounding and reverse causation	[ "OBJECTIVES We sought to investigate the impact of body mass index ( BMI ) on short- and long-term outcomes after initial revascularization with percutaneous transluminal coronary angioplasty ( PTCA ) or coronary artery bypass graft surgery ( CABG ) . BACKGROUND Equivocal results exist on the impact of BMI on the risk of in-hospital complications after PTCA or CABG , and no long-term mortality data exist from a large series of revascularized patients . METHODS From the r and omized series and observational registry of the Bypass Angioplasty Revascularization Investigation ( BARI ) , 2,108 patients who had PTCA and 1,526 patients who had CABG were evaluated by taking their BMI at study entry . They were classified as follows : low ( In-hospital complications and short- and long-term mortalities were compared between levels of BMI within each mode of initial revascularization . RESULTS Among patients who had PTCA , each unit increase in BMI was associated with a 5.5 % lower adjusted risk of a major in-hospital event ( death , myocardial infa rct ion , stroke , coma ) ; among patients who had CABG , no difference in the in-hospital outcome was observed according to BMI . In contrast , BMI was not associated with five-year mortality in the PTCA group ; among the CABG group , adjusted relative risks of five-year cardiac mortality according to levels of BMI were 0.0 ( low ) , 1.0 ( normal ) , 2.02 ( overweight ) , 3.16 ( class I obese ) and 4.85 ( class II/III obese ) ( linear p short- and long-term outcomes after coronary revascularization . These results underscore the need for further research to identify factors responsible for the apparent short-term protective effect of a higher BMI in patients undergoing PTCA and to study the impact of weight reduction on the long-term survival of obese patients undergoing CABG", "Purpose Obesity influences risk stratification in cardiac surgery in everyday practice . However , some studies have reported better outcomes in patients with a high body mass index ( BMI ): this is known as the obesity paradox . The aim of this study was to quantify the effect of diverse degrees of high BMI on clinical outcomes after cardiac surgery , and to assess the existence of an obesity paradox in our patients . Methods A total of 2,499 consecutive patients requiring all types of cardiac surgery with cardiopulmonary bypass between January 2004 and February 2009 were prospect ively studied at our institution . Patients were divided into four groups based on BMI : normal weight ( 18.5–24.9 kg∙m−2 ; n = 523 ; 21.4 % ) , overweight ( 25–29.9kg∙m−2 ; n = 1150 ; 47 % ) , obese ( ≥30–≤34.9kg∙m−2 ; n = 624 ; 25.5 % ) and morbidly obese ( ≥35kg∙m−2 ; n = 152 ; 6.2 % ) . Follow-up was performed in 2,379 patients during the first year . Results After adjusting for confounding factors , patients with higher BMI presented worse oxygenation and better nutritional status , reflected by lower PaO2/FiO2 at 24h and higher albumin levels 48h after admission respectively . Obese patients showed a higher risk for Perioperative Myocardial Infa rct ion ( OR : 1.768 ; 95 % CI : 1.035–3.022 ; p = 0.037 ) and septicaemia ( OR : 1.489 ; 95 % CI : 1.282–1.997 ; p = 0.005 ) . In-hospital mortality was 4.8 % ( n = 118 ) and 1-year mortality was 10.1 % ( n = 252 ) . No differences were found regarding in-hospital mortality between BMI groups . The overweight group showed better 1-year survival than normal weight patients ( 91.2 % vs. 87.6 % ; Log Rank : p = 0.029 . HR : 1.496 ; 95 % CI : 1.062–2.108 ; p = 0.021 ) . Conclusions In our population , obesity increases Perioperative Myocardial Infa rct ion and septicaemia after cardiac surgery , but does not influence in-hospital mortality . Although we found better 1-year survival in overweight patients , our results do not support any protective effect of obesity in patients undergoing cardiac surgery", "BACKGROUND A debate exists whether obesity is a risk factor for operative mortality after coronary artery bypass graft surgery ( CABG ) . The contradictory findings in the literature may largely be attributable to the variety of method ological approaches used to model the association between body mass index ( BMI ) and post-CABG outcomes . This study aims to investigate this association , and to uncover possible explanations for the lack of consensus across prior studies . METHODS Data were prospect ively collected on 80,792 patients who underwent a CABG procedure during a 14-year period at the 45 Department of Veterans Affairs cardiac surgery programs . Generalized additive models were used to estimate the relationship of BMI and outcomes after a CABG procedure . RESULTS We found that the relationship of BMI with post-CABG mortality and morbidity is U-shaped with the minimum risk located around a BMI of 30 kg/m2 , indicating that patients classified as overweight have the lowest risk , and those in the lower end of the obese range do not have seriously elevated risk . This U-shape relationship is significantly nonlinear and robust to adjustment for other risk factors . CONCLUSIONS This study demonstrates that BMI is an independent predictor of mortality and morbidity after CABG surgery . Previous studies that model BMI linearly or as categories can not accurately capture this U-shaped relationship and are unlikely to find a significant contribution by including BMI . Further research is needed to determine the mechanisms of risk for patients with low and high BMI and whether interventions to modify BMI may improve patient outcomes", "In patients with coronary artery disease ( CAD ) , a rate of restenosis as high as 50 % is observed after percutaneous transluminal coronary angioplasty ( PTCA ) . Frequently , this results in further revascularization procedures . Lifestyle intervention has been shown to slow the progression of CAD and to reduce cardiovascular events after myocardial infa rct ion . However , no information exists whether such treatment influences the rate of restenosis in patients with CAD . The present study was performed to investigate the effects of an intensified lifestyle intervention on the need for further revascularization procedures in patients with established CAD after successful PTCA", "OBJECTIVE A high body mass index has been suggested to be protective in patients with coronary artery disease and in those undergoing coronary artery bypass grafting ( CABG ) . However , these conflicting results might be related to the different risk profiles among the various body mass index categories . We sought to clarify the effect of varying degrees of excessive body weight on hard clinical outcomes in patients undergoing CABG . METHODS A retrospective analysis of prospect ively collected data was conducted to investigate the effect of a high body mass index on early and late mortality after first-time isolated CABG . Propensity score matching was used to adjust for confounding factors . RESULTS The study sample consisted of 3269 normal weight , 6662 overweight , 3821 obese , and 211 morbidly obese patients . After matching , early mortality was not affected by overweight ( mean difference , 0.7 % ; 95 % confidence interval [ CI ] , -0.2 % to 1.5 % ) , obesity ( mean difference , 0.5 % ; 95 % CI , -0.7 % to 1.7 % ) , and morbid obesity ( mean difference , 1.6 % ; 95 % CI , -1.0 % to 1.0 % ) , regardless of the patients ' risk profile according to the European system for cardiac operative risk evaluation . Overweight status was not protective for late death ( hazard ratio , 1.05 ; 95 % CI , 0.9 - 1.08 ; P = .4 ) . Compared with normal weight patients , both obese and morbidly obese patients had a higher risk of late death ( hazard ratio , 1.22 ; 95 % CI , 1.07 - 2.66 ; P = .006 for obese patients ; hazard ratio , 1.36 ; 95 % CI , 0.74 - 2.49 ; P = .3 for morbidly obese patients ) . CONCLUSIONS Obesity did not increase operative mortality , but it was associated with reduced late survival in patients undergoing primary isolated CABG . Our results raise concerns in supporting any protective effect of obesity in cardiovascular disease , specifically in patients undergoing surgical myocardial revascularization" ]	41186d32-06ff-11f0-808a-c43d1ab1c353
AIMS We sought to identify the most effective antidysrhythmic drug for pharmacologic cardioversion of recent-onset atrial fibrillation ( AF ) . METHODS AND RESULTS We search ed MEDLINE , Embase , and Web of Science from inception to March 2019 , limited to human subjects and English language . We also search ed for unpublished data . We limited studies to r and omized controlled trials that enrolled adult patients with AF ≤ 48 h and compared antidysrhythmic agents , placebo , or control . We determined these outcomes prior to data extraction : ( i ) rate of conversion to sinus rhythm within 24 h , ( ii ) time to cardioversion to sinus rhythm , ( iii ) rate of significant adverse events , and ( iv ) rate of thromboembolism within 30 days . We extracted data according to PRISMA -NMA and appraised selected trials using the Cochrane review h and book . The systematic review initially identified 640 studies ; 30 met inclusion criteria . Twenty-one trials that r and omized 2785 patients provided efficacy data for the conversion rate outcome . Bayesian network meta- analysis using a r and om-effects model demonstrated that ranolazine + amiodarone intravenous ( IV ) [ odds ratio ( OR ) 39.8 , 95 % credible interval ( CrI ) 8.3 - 203.1 ] , vernakalant ( OR 22.9 , 95 % CrI 3.7 - 146.3 ) , flecainide ( OR 16.9 , 95 % CrI 4.1 - 73.3 ) , amiodarone oral ( OR 10.2 , 95 % CrI 3.1 - 36.0 ) , ibutilide ( OR 7.9 , 95 % CrI 1.2 - 52.5 ) , amiodarone IV ( OR 5.4 , 95 % CrI 2.1 - 14.6 ) , and propafenone ( OR 4.1 , 95 % CrI 1.7 - 10.5 ) were associated with significantly increased likelihood of conversion within 24 h when compared to placebo/control . Overall quality was low , and the network exhibited inconsistency . Probabilistic analysis ranked vernakalant and flecainide high and propafenone and amiodarone IV low . CONCLUSION For pharmacologic cardioversion of recent-onset AF within 24 h , there is insufficient evidence to determine which treatment is superior . Vernakalant and flecainide may be relatively more efficacious agents . Propafenone and IV amiodarone may be relatively less efficacious . Further high- quality study is necessary	[ "AIM The aim of the present study was to compare the safety and efficacy of amiodarone and procainamide in the acute cardiology setting . METHODS The study population consisted of 223 patients with symptomatic atrial fibrillation ( AF ) . After administration of digoxin for ventricular rate control , all patients who failed to restore sinus rhythm ( SR ) were r and omized into 2 groups : group A ( 113 patients ) were administered 300 mg amiodarone intravenously over 30 min and , in case of failure to restore SR , amiodarone of 20 mg/kg/24 h was administered intravenously . Group B ( 110 patients ) were intravenously administered a bolus dose of 1 gm procainamide , at an infusion rate 50/mg/min , and , in case of failure to restore SR , 2 mg/min for the next 24 h. RESULTS The rate of cardioversion to SR was similar between amiodarone ( 81.4 % ) and procainamide ( 82.7 % ) ( P = NS ) . Procainamide loading recorded faster cardioversion times than amiodarone loading ( P=0.02 ) , but there was no significant difference after that . Amiodarone caused a significant decrease on systolic blood pressure compared to procainamide for the first 18 h ( P diastolic blood pressure for the first 6 h ( P Side-effects for either medication were sparse . The only real prognostic factor for successful cardioversion remains the size of left atrium . CONCLUSION Both drugs were equally effective in restoring SR , though procainamide acts quicker in the loading phase . Both medications are safe and side effects develop only in the maintenance phase", "Background Indirect comparisons are becoming increasingly popular for evaluating medical treatments that have not been compared head-to-head in r and omized clinical trials ( RCTs ) . While indirect methods have grown in popularity and acceptance , little is known about the fragility of confidence interval estimations and hypothesis testing relying on this method . Methods We present the findings of a simulation study that examined the fragility of indirect confidence interval estimation and hypothesis testing relying on the adjusted indirect method . Findings Our results suggest that , for the setting s considered in this study , indirect confidence interval estimation suffers from under-coverage while indirect hypothesis testing suffers from low power in the presence of moderate to large between- study heterogeneity . In addition , the risk of overestimation is large when the indirect comparison of interest relies on just one trial for one of the two direct comparisons . Interpretation Indirect comparisons typically suffer from low power . The risk of imprecision is increased when comparisons are unbalanced", "BACKGROUND A prospect i ve , r and omized study was conducted to evaluate the efficacy and tolerability of oral propafenone and quinidine for the conversion of paroxysmal atrial fibrillation ( AF ) . METHODS Eighty one consecutive patients ( female/male 46/35 ; mean age 64.0 + /- 11.6 ) , admitted to hospital with AF lasting no longer than 48 hours , were r and omized in terms of their pharmacological therapy . Forty three patients ( 55 % ) were r and omly assigned to Group I and received propafenone 600 mg orally as the initial therapy , with an additional dose of 300 mg after eight hours , if the sinus rhythm had not been restored by then . Thirty eight patients ( 45 % ) ( Group II ) received 1 mg digoxin IV followed by an oral loading of quinidine ( 400 mg followed by 200 mg every two hours ) . RESULTS The conversion rate assessed after 24 hours was the same in both groups ( Gr . I vs. Gr . II : 90.7 vs. 91.4 % ) , with the same number of mild side effects ( Gr . I vs. Gr . II : 37.2 % vs. 45.7 % ) . No life-threatening adverse events were reported . Propafenone achieved a higher efficacy rate during the first eight hours ( 83.3 vs. 54.3 % ; p = 0.01 ) , with a significantly shorter time required to sinus rhythm recovery throughout the study period , with a median time of 165 min ( 95 % confidence interval 120 - 278 ) vs. 360 min ( 95 % confidence interval 298 - 650 ; p effectiveness of propafenone than quinidine in early sinus rhythm restoration in patients with : no structural heart disease , in those with an AF duration shorter than 12 hours , and in patients with an ejection fraction > 55 % . CONCLUSIONS Although both drugs revealed the same effectiveness , the conversion to sinus rhythm in the group treated with propafenone was observed more quickly despite the longer paroxysmal AF episode duration", "BACKGROUND Drugs currently available for the acute treatment of paroxysmal atrial fibrillation have significant limitations . We assessed the safety and effectiveness of intravenous magnesium sulfate versus diltiazem therapy in patients with prolonged episodes of paroxysmal atrial fibrillation . METHODS In a prospect i ve r and omized trial , 46 symptomatic patients presenting with paroxysmal atrial fibrillation were given intravenous magnesium sulfate ( n=23 ) or diltiazem ( n=23 ) therapy . Primary outcome measures were effects on ventricular rate control and proportion of patients restored to sinus rhythm at 6 h after initiation of treatment . RESULTS There were no differences in baseline characteristics between the two groups . Both forms of treatment were well tolerated , with no adverse clinical events . Both drugs had similar efficacy in reducing the ventricular rate at the first hour of treatment ( P restoration of sinus rhythm was observed in a significantly higher proportion of patients in the magnesium group compared with the diltiazem group [ 13 of 23 patients , ( 57 % ) , versus five of 23 patients , ( 22 % ) , P=0.03 ] . CONCLUSIONS Magnesium sulfate favorably affects rate control and seems to promote the conversion of long lasting episodes of paroxysmal atrial fibrillation to sinus rhythm , representing a safe , reliable and cost-effective alternative treatment strategy to diltiazem", "AIM The aim of our study was to compare the efficacy and safety of ibutilide and amiodarone ( intravenously ) in converting recent-onset atrial fibrillation ( AF ) and atrial flutter ( Af ) to sinus rhythm ( SR ) . METHODS The study was prospect i ve , r and omized and included 152 ( 103 men and 49 women ) consecutive patients with AF or Af of 3 - 48 h duration . Ibutilide is a selective class III antiarrhythmic agent which when administered intravenously can terminate AF and Af . Amiodarone is also a class III antiarrhythmic agent that when given intravenously or orally has proved to be more effective than other agents in terminating AF and Af [ B.N. Singh , F.V. Mody , B. Lopez , J.S. Sarma . Antiarrhythmic agents for atrial fibrillation : focus on prolonging atrial repolarization . Am J Cardiol 1999 Nov 4 ; 84 : 161R-173R . ] . Seventy-nine patients ( 56 with AF and 23 with Af ) that consisted group A were treated with ibutilide . Seventy-three ( 52 with AF and 21 with Af ) consisted group B and were treated with intravenous infusion of amiodarone . RESULTS The conversion rate of group A ( ibutilide ) was significantly higher than the conversion rate of group B ( amiodarone ) ( 80 % vs. 57 % , p=0.0054 ) . As regards the kind of arrhythmia separately , for AF there was n't significant difference ( 77 % vs. 69 % , p = ns ) whereas for Af ibutilide was superior to amiodarone ( 87 % vs. 29 % , p=0.003 ) . The conversion rates of ibutilide did n't differ for AF and Af ( 77 % vs. 87 % , p = ns ) . CONCLUSIONS Ibutilide is more effective than amiodarone in converting recent-onset Af to SR whereas both drugs are equally effective in converting recent-onset AF to SR", "Introduction Emergency department ( ED ) cardioversion ( EDCV ) and discharge of patients with recent onset atrial fibrillation or atrial flutter ( AF ) has been shown to be a safe and effective management strategy . This study examines the impact of such aggressive ED management on hospital charges . Methods : A r and om sample of 300 AF patients were identified from an ED electronic data base and screened for timing of onset of their symptoms . Patients were considered eligible for EDCV if either nursing or physician notes documented an onset of symptoms less than 48 hours prior to ED presentation and the patient was less than 85 years of age . An explicit chart review was then performed to determine patient management and disposition . Cardioversion attempts were defined as ED administration of procainamide , flecainide , propafenone , ibutilide , amiodarone or direct current cardioversion ( DCCV ) . Total hospital charges for each patient were obtained from the hospital billing office . Differences across medians were analyzed utilizing through Wilcoxon rank sum tests and chi square . Results : A total of 51 patients were included in the study . EDCV was attempted on 24 ( 47 % ) patients , 22 ( 92 % ) were successfully cardioverted to normal sinus rhythm ( NSR ) . An additional 12 ( 23 % ) spontaneously converted to NSR . Twenty ( 91 % ) of those successfully cardioverted were discharged from the ED along with 4 ( 33 % ) of those spontaneously converting . Pharmacologic cardioverson was attempted in six patients and was successful in three ( 50 % ) , one after failed DCCV attempt . Direct current cardioversion was attempted in 21 ( 88 % ) and was successful in 19 ( 90 % ) , two after failed pharmacologic attempts . Median charges for patients cardioverted and discharged from the ED were $ 5,460 ( IQR $ 4,677–$6,190 ) . Median charges for admitted patients with no attempt at cardioversion were $ 23,202 ( IQR $ 19,663–$46,877 ) . Median charges for patients whose final ED rhythm was NSR were $ 5,641 ( IQR $ 4,638–$12,339 ) while for those remaining inAF median charges were $ 30,299 ( IQR $ 20,655 – $ 69,759 ) . Conclusion : ED cardioversion of recent onset AF patients results in significant hospital savings ", "OBJECTIVE To investigate whether an oral loading dose of flecainide is as safe and effective as intravenous flecainide for the cardioversion of acute atrial fibrillation . DESIGN Prospect i ve , r and omised , double blind , double placebo study . SETTING Cardiac care unit of a large district general hospital in the UK . PATIENTS AND METHODS 79 patients presenting with symptomatic acute atrial fibrillation : patients were given either intravenous flecainide ( n = 39 ) or a solution of oral flecainide ( n = 40 ) , with appropriate placebos . All patients were heparinised during the study . PRIMARY OUTCOME MEASURES Safety ; mean time to cardioversion ; proportion of patients restored to sinus rhythm at two hours and eight hours after treatment . Analysis was by intention to treat . RESULTS There were no differences in baseline characteristics between the oral and intravenous groups . Both forms of flecainide were well tolerated , with no adverse clinical events during the study . The mean time to cardioversion was 110 minutes in the oral group and 52 minutes in the intravenous group ( p = 0.002 ) . Two hours after treatment , 27 of the 40 patients in the oral group ( 68 % ) and 25 of the 39 in the intravenous group ( 64 % ) had reverted to sinus rhythm ( p = 0.74 ) . Eight hours after treatment , 30 patients in the oral group ( 75 % ) and 28 in the intravenous group ( 72 % ) had reverted to sinus rhythm ( p = 0.76 ) . CONCLUSIONS Intravenous flecainide restored sinus rhythm more rapidly than oral flecainide , but at two hours and eight hours after treatment there was no difference in the proportion of patients cardioverted by the two approaches . These results suggest a role for oral loading doses of flecainide in the treatment of acute or symptomatic paroxysmal atrial fibrillation", "The appropriate treatment for the restoration of sinus rhythm in patients with atrial fibrillation ( AF ) of recent onset is still the subject of controversy . In this prospect i ve , r and omized , single-blind , placebo-controlled clinical study , we investigated the effectiveness and safety of procainamide , propafenone , and amiodarone , administered intravenously , for the conversion of recent-onset AF . We enrolled 362 consecutive patients ( 183 men ; age 34 to 86 years ; mean 65+/-10 ) with AF duration of no > 48 hours . Of these patients , 89 were given procainamide , 91 propafenone , 92 amiodarone , and 90 placebo . Treatment was considered successful if conversion to sinus rhythm was achieved within the 24-hour study period . Baseline clinical characteristics were similar in the 4 groups . The treatment was successful in 61 of the 89 patients who received procainamide ( 68.53 % ; median time 3 hours ) , 73 of the 91 patients who received propafenone ( 80.21 % ; median time 1 hour ) , 82 of the 92 patients who received amiodarone ( 89.13 % ; median time 9 hours ) , and 55 of the 90 patients who received placebo ( 61.11 % ; median time 17 hours ; p placebo ; p amiodarone and propafenone vs procainamide ) . In conclusion , all 3 medications , when administered intravenously , are effective in the restoration of sinus rhythm in recent-onset AF . Amiodarone and propafenone are more effective whereas procainamide and propafenone are faster", "INTRODUCTION Paroxysmal atrial fibrillation ( AF ) may progress to persistent AF . We studied the clinical correlates and the effect of rhythm-control strategy on AF progression . METHODS RecordAF was a worldwide prospect i ve survey of AF management . Consecutive eligible patients with recent-onset AF were included and allocated to rate or rhythm control according to patient/physician choice . A total of 2,137 patients were followed up for 12 months . Atrial fibrillation progression was defined as a change from paroxysmal to persistent/permanent AF . RESULTS Progression of AF occurred in 318 patients ( 15 % ) after 1 year . Patients with AF progression were older ; had a higher diastolic blood pressure ; and more often had a history of coronary artery disease , stroke or transient ischemic attack , hypertension , or heart failure . Patients treated with rhythm control were less likely to show progression than those treated only with rate control ( 164/1542 [ 11 % ] vs 154/595 [ 26 % ] , P history of heart failure ( odds ratio [ OR ] 2.2 , 95 % CI 1.7 - 2.9 , P history of hypertension ( OR 1.5 , 95 % CI 1.1 - 2.0 , P = .01 ) , and rate control rather than rhythm control ( OR 3.2 , 95 % CI 2.5 - 4.1 , P AF progression . The propensity score-adjusted OR of AF progression in patients with rate rather than rhythm control was 3.3 ( 95 % CI 2.4 - 4.6 , P AF progression , rhythm control is associated with lower risk of AF progression", "AIM Oral propafenone is effective in restoring sinus rhythm however the proarrhythmic effects are still unknown . The Safety Antiarrhythmic Therapy Evaluation ( SATE ) trial was a prospect i ve r and omized placebo-controlled multicentre study which evaluated the safety of acute oral loading dose of propafenone in patients with recent onset atrial fibrillation . Secondary end-points were to evaluate the effect of digitalis added to propafenone in ventricular rate control and the efficacy of propafenone alone or added to digitalis compared with efficacy of digitalis plus quinidine . METHODS AND RESULTS 246 patients ( 126 male ; 58+/-11 years ) with atrial fibrillation of allocated to one of four groups : digitalis 0.75 - 1 mg i.v . plus quinidine 1100 mg ( D+Q , 70 patients ) ; propafenone 450 - 600 mg orally ( PNF , 66 patients ) ; propafenone 450 - 600 mg orally plus digitalis 0.750 - 1 mg i.v . ( PNF+D , 70 patients ) ; placebo ( Pl , 40 patients ) . All patients underwent 24-h ECG Holter monitoring . Safety was assessed by evaluating the appearance of adverse events classified as mild , moderate and severe . No severe adverse events were reported . Short lasting asymptomatic atrial flutter episodes with atrio-ventricular conduction > or = 2:1 were observed in 14 % of the D+Q group , 21 % PNF , 18 % PNF+D and in 8 % Pl . One patient in the D+Q group and four in the PNF+D group showed asymptomatic runs of 3 - 4 ventricular ectopic beats . Reversible sinus atrial blocks ( ventricular rate was similar in the four study groups . At 3 h the high efficacy of propafenone was confirmed . At the 24th hour no differences were found between active treatment and placebo arms . CONCLUSION Propafenone in a single oral loading dose is safe and promptly effective in patients with recent onset atrial fibrillation", "BACKGROUND Spontaneous conversion of recent onset paroxysmal atrial fibrillation to normal sinus rhythm occurs commonly and is not affected by low-dose amiodarone treatment . METHODS In a r and omized , placebo-controlled trial of 100 patients with paroxysmal atrial fibrillation of recent onset ( we compared the effects of treatment with continuous intravenous amiodarone 125 mg per hour ( total 3 g ) and intravenous placebo . Patients in the placebo group who did not convert to normal sinus rhythm within 24 h were started on amiodarone therapy . RESULTS Conversion to normal sinus rhythm occurred within 24 h in 32 of 50 patients ( 64 % ) in the placebo group , most of whom converted within 8 h. Lower conversion rates were observed in patients with hypertension , ischaemic heart disease or congestive heart failure and in patients with echocardiographic findings of left atrial diameter above 45 mm , ejection fraction below 45 % or significant mitral regurgitation . However , in most patients these clinical or echocardiographic risk factors of decreases in conversion rate were not present . In such patients the spontaneous conversion rate was approximately 90 % . The conversion rate during 24 h of treatment in the amiodarone group was 92 % ( P=0.0017 , compared to the placebo group ) . In this group , the conversion rate was largely unaffected by baseline characteristics . Of the 18 patients who did not convert with placebo , 15 ( 85 % ) converted after being crossed over to amiodarone . All patients not responding to high-dose amiodarone were in chronic atrial fibrillation within 1 month . In patients still in atrial fibrillation after 8 h of treatment , the pulse rate decreased significantly more in the amiodarone as compared to the placebo group ( 83+/-15 vs 114+/-20 beats . min(-1 ) , P=0.0014 ) . CONCLUSION The spontaneous conversion of recent onset paroxysmal atrial fibrillation is high and approaches 90 % in specific clinical and echocardiographically defined subgroups . Intravenous high-dose amiodarone safely facilitates conversion of paroxysmal atrial fibrillation . However , such treatment should be reserved for patients with unfavourable risk factor profiles , not converting during 8 h of observation or requiring rate control", "STUDY OBJECTIVE A prospect i ve , r and omized controlled trial of new-onset atrial fibrillation was conducted to compare the efficacy and safety of sotalol and amiodarone ( active treatment ) with rate control by digoxin alone for successful reversion to sinus rhythm at 48 hours . METHODS We prospect ively r and omly assigned 120 patients with atrial fibrillation of less than 24 hours ' duration to treatment with sotalol , amiodarone , or digoxin using a single intravenous dose followed by 48 hours of oral treatment . Patients had ECG monitoring for 48 hours , and time of reversion , adequacy of rate control , and numbers of adverse events were compared . After 48 hours , those still in atrial fibrillation underwent cardioversion according to a st and ardized protocol . After 48 hours of therapy and attempted cardioversion , the number of patients whose rhythms had successfully reverted were compared . RESULTS There was a significant reduction in the time to reversion with both sotalol ( 13 . 0+/-2.5 hours , P amiodarone ( 18.1+/-2.9 hours , P digoxin only ( 26.9+/-3.4 hours ) . By 48 hours , the active treatment group was significantly more likely to have reverted to sinus rhythm than the rate control group ( 95 % versus 78 % , P ventricular rate control in the sotalol group at both 24 and 48 hours compared with those who received either amiodarone or digoxin . There were also fewer adverse events in the active treatment group compared with the rate control group . CONCLUSION Immediate pharmacologic therapy for new-onset atrial fibrillation with class III antiarrhythmic drugs ( sotalol or amiodarone ) improves complication-free 48-hour reversion rates compared with rate control with digoxin", "AIMS Amiodarone is used commonly for pharmacological cardioversion of atrial fibrillation ( AF ) , but it is limited by moderate efficacy and delayed action . Ranolazine and amiodarone are markedly synergistic in suppressing experimental AF in vitro , yet the clinical efficacy of ranolazine combined with amiodarone for AF conversion has only undergone minimal investigation . This prospect i ve , single-blinded , r and omized study compared the safety and efficacy of ranolazine added to amiodarone vs. amiodarone alone for conversion of recent-onset AF . METHODS AND RESULTS We enroled 121 patients ( 64 ± 10 years , 45 % male ) with recent-onset ( Patients received either 24 h amiodarone infusion ( loading dose 5 mg/kg followed by maintenance dose of 50 mg/h ; n = 60 ) , or amiodarone infusion at the same dosage plus a single oral dose of ranolazine 1500 mg ( n = 61 ) . Patients in the amiodarone plus ranolazine group compared with the amiodarone-only group showed significantly higher conversion rates at 24 h ( 87 vs. 70 % , respectively ; P = 0.024 ) and at 12 h ( 52 vs. 32 % ; P = 0.021 ) , and shorter time to conversion ( 10.2 ± 3.3 vs. 13.3 ± 4.1 h ; P = 0.001 ) . Subgroup analysis identified higher 24 h conversion in patients with left atrial ( LA ) diameter > 46 mm who received the combination treatment vs. amiodarone alone ( 81 vs. 54 % ; P = 0.02 ) , whereas the efficacy of the two interventions did not differ among patients with LA diameter ≤46 mm ( P = 0.77 ) . There was modest QT prolongation in both the groups , no serious adverse reactions , and no pro-arrhythmic events . CONCLUSION Addition of ranolazine to amiodarone was safe and well tolerated in this study , and it demonstrated efficacy superior to amiodarone alone for conversion of recent-onset AF . These findings may have clinical implication s by offering a simple therapeutic manoeuvre to enhance amiodarone 's effectiveness for conversion of AF", "STUDY OBJECTIVE To determine the relative effectiveness of a verapamil-quinidine sequential combination versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation ( PAF ) . METHOD This prospect i ve , double-blind , r and omized , controlled trial involved patients , aged 18 to 75 years , with new-onset ( Consenting patients were r and omly assigned to receive rapid digitalization ( 1.0 mg over 2 hours ) or i.v . verapamil ( sequential 5-mg boluses up to 20 mg ) . After ventricular rate was controlled ( quinidine ( 200 mg ) was initiated and repeated every 2 hours until conversion to normal sinus rhythm ( NSR ) occurred , until 1 g of quinidine was administered , or until adverse effects supervened . Heart rate , blood pressure , cardiac rhythm , time to conversion , and adverse effects were documented . RESULTS Forty-four patients received the study drugs . Three were withdrawn , leaving 19 in the verapamil-quinidine ( VER-Q ) group and 22 in the digoxin-quinidine ( DIG-Q ) group . Sixteen patients ( 84 % ) in the VER-Q group and 10 ( 45 % ) in the DIG-Q group converted to NSR within 6 hours ( P Mean time to conversion ( + /-SD ) was 185 + /- 146 minutes for VER-Q and 368 + /- 386 minutes for DIG-Q patients ( P = NS ) . Twelve VER-Q patients ( 63 % ) and 6 DIG-Q patients ( 27 % ) were discharged from the ED ( P Minor adverse effects were more common in the VER-Q group . No mortality or significant morbidity occurred . CONCLUSION The sequential combination of verapamil and quinidine , in the doses studied , is an effective treatment for PAF and is superior to digoxin-quinidine . Digoxin should no longer be considered the treatment of choice for uncomplicated PAF", "Background : Amiodarone ( AMIO ) is for many years effectively used to control ventricular rate during atrial fibrillation ( AF ) and to convert it into sinus rhythm . However , due to its delayed onset of action , ranolazine ( RAN ) , a new antianginal agent with atrial‐selective electrophysiologic properties , has recently been attempted as add‐on therapy with AMIO to facilitate AF conversion . Methods : To establish the role of this combination therapy , we enrolled 173 consecutive patients ( 68 ± 10 years , 54 % male ) with recent‐onset ( Patients were r and omized to intravenous AMIO ( loading dose 5 mg/kg in 1 hour followed by 50 mg/h ; n = 81 ) , or AMIO plus a single oral dose of RAN 1 g ( n = 92 ) . Results : Mean left atrial diameter did not significantly differ between groups , AMIO and AMIO + RAN ( 4.2 ± 0.5 cm vs 4.1 ± 0.4 cm , P = 0.18 ) . The AMIO + RAN group compared with the AMIO‐only group showed significantly shorter time to conversion ( 8.6 ± 2.8 hours vs 19.4 ± 4.4 hours , P higher conversion rate at 24 hours ( 98 % vs 58 % , P did not markedly vary between the two groups and ranged within moderately reduced values . No serious clinical ly evident adverse effects were observed in any of the patients receiving either AMIO or the combination treatment . Conclusions : Our data demonstrate faster sinus rhythm restoration and enhanced conversion rate of AF after AMIO plus RAN in patients with preserved ejection fraction and left atrial size , implicating a synergistic effect of the two agents", "Background Direct current cardioversion ( DCC ) has been shown to be effective for the management of atrial fibrillation ( AF ) in the emergency department ( ED ) . Pharmacological cardioversion was compared with a strategy including DCC on patients with uncomplicated , recent-onset ( managed in a short observation unit ( SOU ) . Methods A prospect i ve observational study was undertaken over a period of 13 months in two institutions . A DCC-centred protocol was applied to 171 AF cases in a hospital ( DCC-cohort ) and pharmacological cardioversion to 151 AF cases in another hospital ( P-cohort ) . Patients remaining in AF after 24 h were admitted . The outcomes were rate of discharge in sinus rhythm , length of stay in the ED-SOU , rate of hospitalisation and complications of treatment . Data collected were analysed according to Student t test and χ2 statistics . Results Discharge in sinus rhythm was achieved in 159/171 cases in the DCC-cohort and 77/151 cases in the P-cohort ( 93 % vs 51 % ; number needed to treat ( NNT ) 2.4 ; 95 % CI 2.0 to 3.1 , p mean length of stay was 7 + 7 h in the DCC-cohort and 9 + 6 h in the P-cohort ( p=0.43 ) . Eleven cases from the DCC-cohort and 67 from the P-cohort were admitted ( admission rate 6 % vs 44 % ; NNT 2.6 ; 95 % CI 2.2 to 3.5 , p short-term complications occurred in the DCC-cohort and five in the P-cohort ( 2 % vs 3 % , p=0.59 ) . Two strokes were registered in the DCC-cohort during 6-month follow-up ( p undefined ) . Conclusions Electrical cardioversion of recent-onset AF in the SOU is safe , effective and reduces hospitalisations . Further studies are needed to identify the most cost-effective strategy for the management of AF patients in emergency setting", "We r and omized 61 patients with paroxysmal atrial fibrillation ( AF ) ( sotalol or quinidine treatment . Conversion of rhythm was recorded by Holter monitoring . The starting 80 mg dose of sotalol was repeated at 2 , 6 , and 10 hours if AF persisted ( heart rate > 80 beats/min ) , and if systolic blood was > or = 120 mm Hg . In the quinidine group , if heart rate > 100 beats/min , it was decreased with intravenous digoxin , whereafter 200 mg of oral quinidine sulfate was given maximally 3 times , each dose 2 hours apart . Conversion of AF to sinus rhythm occurred in 17 or 33 patients ( 52 % ) taking sotalol , and in 24 of 28 patients ( 86 % ) taking quinidine ( p Electric cardioversion was necessary in 39 % of the former and in 14 % of the latter group . The mean delay from first trial drug to sinus rhythm with the trial medication was 10.2 + /- 7.6 hours in the sotalol group and 4.0 + /- 2.9 hours in the quinidine group ( p sotalol ( 48 % ) because of asymptomatic bradycardia or hypotension , and in 20 taking quinidine ( 71 % ) because of rhythm conversion . Asymptomatic wide complex tachycardia ( QRS > 0.12 second ) was found in 13 % and 27 % of patients taking sotalol and quinidine , respectively . The longest RR intervals were 6.4 and 3.8 seconds in the sotalol and quinidine groups , respectively . Oral sotalol did not appear as effective as quinidine sulfate treatment in conversion of paroxysmal AF . ( ABSTRACT TRUNCATED AT 250 WORDS", "The efficacy of amiodarone has been proved in long-term maintenance of sinus rhythm ( SR ) in patients with paroxysmal atrial fibrillation ( AF ) . The present study evaluates the efficacy and safety of a single oral dose of amiodarone in patients with recent-onset AF ( amiodarone or placebo . Conversion to SR was verified by 24-hour Holter monitoring . Ten patients were excluded because of SR in the beginning of monitoring or technical failure during Holter monitoring . The remaining study groups were comparable ( n = 31 for each ) , except that in the placebo group beta blockers were more common . The patients receiving amiodarone converted to SR more effectively than those receiving placebo ( p amiodarone group and 20 % in the placebo group ( Holter successful ) had converted to SR , whereas after 24 hours the corresponding figures were 87 % and 35 % , respectively . The median time for conversion ( 8.7 hours for amiodarone and 7.9 hours for placebo ) did not differ in the groups . Amiodarone was hemodynamically well tolerated , and the number of adverse events in the study groups was similar . Amiodarone as a single oral dose of 30 mg/kg appears to be effective and safe in patients with recent-onset AF", "Aims Ibutilide is a rapid‐acting antiarrhythmic drug with worldwide use for conversion of recent‐onset atrial fibrillation . Vernakalant , approved in the EU in 2010 , is likewise used intravenously , with proven efficacy and safety compared with placebo and amiodarone in r and omized clinical trials . The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent‐onset atrial fibrillation treated with vernakalant or ibutilide . Methods and results A r and omized controlled trial registered at clinical trials.gov ( NCT01447862 ) was performed in 100 patients with recent‐onset atrial fibrillation treated at the emergency department of a tertiary care hospital . Patients received up to two short infusions of vernakalant ( n = 49 ; 3 mg/kg followed by 2 mg/kg if necessary ) or ibutilide ( n = 51 ; 1 mg followed by another 1 mg if necessary ) according to the manufacturer 's instructions . Clinical and laboratory variables , adverse events , conversion rates , and time to conversion were recorded . Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the ibutilide group ( median time : 10 vs. 26 min , P = 0.01 ) , and likewise the conversion success within 90 min was significantly higher in the vernakalant group ( 69 vs. 43 % , log‐rank P = 0.002 ) . No serious adverse events occurred . Conclusion Vernakalant was superior to ibutilide in converting recent‐onset atrial fibrillation to sinus rhythm in the emergency department setting", "OBJECTIVES This r and omized double-blind study compared the efficacy and safety of intravenous vernakalant and amiodarone for the acute conversion of recent-onset atrial fibrillation ( AF ) . BACKGROUND Intravenous vernakalant has effectively converted recent-onset AF and was well tolerated in placebo-controlled studies . METHODS A total of 254 adult patients with AF ( 3 to 48 h duration ) eligible for cardioversion were enrolled in the study . Patients received either a 10-min infusion of vernakalant ( 3 mg/kg ) followed by a 15-min observation period and a second 10-min infusion ( 2 mg/kg ) if still in AF , plus a sham amiodarone infusion , or a 60-min infusion of amiodarone ( 5 mg/kg ) followed by a maintenance infusion ( 50 mg ) over an additional 60 min , plus a sham vernakalant infusion . RESULTS Conversion from AF to sinus rhythm within the first 90 min ( primary end point ) was achieved in 60 of 116 ( 51.7 % ) vernakalant patients compared with 6 of 116 ( 5.2 % ) amiodarone patients ( p rapid conversion ( median time of 11 min in responders ) and was associated with a higher rate of symptom relief compared with amiodarone ( 53.4 % of vernakalant patients reported no AF symptoms at 90 min compared with 32.8 % of amiodarone patients ; p = 0.0012 ) . Serious adverse events or events leading to discontinuation of study drug were uncommon . There were no cases of torsades de pointes , ventricular fibrillation , or polymorphic or sustained ventricular tachycardia . CONCLUSIONS Vernakalant demonstrated efficacy superior to amiodarone for acute conversion of recent-onset AF . Both vernakalant and amiodarone were safe and well tolerated in this study . ( A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation [ AVRO ] ; NCT00668759 )", "OBJECTIVES The goal of the present study was to assess the efficacy and safety of intravenous tedisamil , a new antiarrhythmic compound , for conversion of recent-onset atrial fibrillation ( AF ) or atrial flutter ( AFL ) to normal sinus rhythm ( NSR ) . BACKGROUND Tedisamil is a novel antiarrhythmic drug with predominantly class III activity . Its efficacy and safety for conversion of recent onset AF or AFL to NSR is not known . METHODS This was a multicenter , double-blind , r and omized , placebo-controlled , sequential ascending dose-group trial . A total of 201 patients with symptomatic AF or AFL of 3 to 48 h duration were enrolled in a two-stage study . During stage 1 , patients were r and omized to receive tedisamil at 0.4 mg/kg body weight or matching placebo ; during stage 2 , patients received tedisamil at 0.6 mg/kg body weight or matching placebo . Treatments were given as single intravenous infusions . The primary study end point consisted of the percentage of patients converting to NSR for at least 60 s within 2.5 h. RESULTS Of 175 patients representing the intention-to-treat sample , conversion to NSR was observed in 41 % ( 25/61 ) of the tedisamil 0.4 mg/kg group , 51 % ( 27 of 53 ) of the tedisamil 0.6 mg/kg group , and 7 % ( 4/59 ) of the placebo group ( p Average time to conversion was 35 min in patients receiving tedisamil . There were two instances of self-terminating ventricular tachycardia : one episode of torsade de pointes and one of monomorphic ventricular tachycardia , both in patients receiving 0.6 mg/kg tedisamil . CONCLUSIONS Tedisamil at dosages of 0.4 and 0.6 mg/kg was superior to placebo in converting AF or AFL . Tedisamil has a rapid onset of action leading to conversion within 30 to 40 min in the majority of responders", "In a prospect i ve , single-blind trial , we r and omized 150 consecutive symptomatic patients with acute ( flecainide , propafenone , or amiodarone . Flecainide and propafenone were administered as a bolus dose of 2 mg/kg in 20 minutes . A second bolus dose of 1 mg/kg in 20 minutes was administered if conversion to sinus rhythm was not achieved after 8 hours . Amiodarone was administered as a bolus of 5 mg/kg in 20 minutes followed by a continuous infusion of 50 mg/hour . By the end of a 12-hour observation period , conversion to sinus rhythm was achieved in 45 patients ( 90 % ) in the flecainide group , 36 ( 72 % ) in the propafenone group , and 32 ( 64 % ) in the amiodarone group ( p = 0.008 for the overall comparison , p = 0.002 for flecainide vs amiodarone , p = 0.022 for flecainide vs propafenone , and p = 0.39 for propafenone vs amiodarone ) . When compared with amiodarone , this higher reversion rate with flecainide was present from the first hour of the study period . However , only after administering the second bolus was there a significant difference between flecainide and propafenone . Median time to conversion to sinus rhythm was different among groups ( p flecainide ( 25 minutes ; range 4 to 660 ) and propafenone ( 30 minutes ; range 10 to 660 ) groups than in the amiodarone group ( 333 minutes ; range 15 to 710 ; p Flecainide , at the doses administered in this study , is more effective than propafenone and amiodarone for conversion of acute atrial fibrillation to sinus rhythm . Propafenone and amiodarone have similar conversion rates , although propafenone was faster in achieving the conversion to sinus rhythm", "AIMS Since atrial fibrillation ( AF ) is associated with increased risks of cardiovascular and cerebrovascular complications , estimations on the number of individuals with AF are relevant to healthcare planning . We aim ed to project the number of individuals with AF in the Netherl and s and in the European Union from 2000 to 2060 . METHODS AND RESULTS Age- and sex-specific AF prevalence estimates were obtained from the prospect i ve community-based Rotterdam Study . Population projections for the Netherl and s and the European Union were obtained from the European Union 's statistics office . In the age stratum of 55 - 59 years , the prevalence of AF was 1.3 % in men ( 95 % CI : 0.4 - 3.6 % ) and 1.7 % in women ( 95 % CI : 0.7 - 4.0 % ) . The prevalence of AF increased to 24.2 % in men ( 95 % CI : 18.5 - 30.7 % ) , and 16.1 % in women ( 95 % CI : 13.1 - 19.4 % ) , for those > 85 years of age . This age- and sex-specific prevalence remained stable during the years of follow-up . Furthermore , we estimate that in the European Union , 8.8 million adults over 55 years had AF in 2010 ( 95 % CI : 6.5 - 12.3 million ) . We project that this number will double by 2060 to 17.9 million ( 95 % CI : 13.6 - 23.7 million ) if the age- and sex-specific prevalence remains stable . CONCLUSION We estimate that from 2010 to 2060 , the number of adults 55 years and over with AF in the European Union will more than double . As AF is associated with significant morbidities and mortality , this increasing number of individuals with AF may have major public health implication", "UNLABELLED The efficacy and safety of intravenous propafenone , amiodarone , or placebo were compared in the treatment of atrial fibrillation ( AF ) of recent onset ( duration METHODS 143 patients ( 77 men , mean age 63 + /- 12 years ) were studied , of whom 46 received propafenone ( 2 mg/kg over 15 minutes followed by 10 mg/kg over the next 24 hours ) , 48 received amiodarone ( 300 mg intravenously over 1 hour , followed by 20 mg/kg over the next 24 hours , plus 1,800 mg/day orally , in 3 divided doses ) , and 49 received placebo ( the equivalent amount of saline i.v . over 24 hours ) . Digoxin was administered to all patients who had not previously received it . RESULTS Conversion to normal sinus rhythm occurred in 36 of 46 patients ( 78.2 % ) receiving propafenone , in 40 of 48 patients ( 83.3 % ) receiving amiodarone , and in 27 of the 49 ( 55.10 % ) controls ( P placebo , between drugs NS ) . The mean time to conversion was 2 + /- 3 hours for propafenone , 7 + /- 5 hours for amiodarone , and 13 + /- 9 for placebo ( P smaller atria than those who did not ( diameter : 42.7 + /- 5 vs 47.2 + /- 7 mm , P amiodarone group because of an allergic reaction and in two patients in the propafenone group because of excessive QRS widening . No side effects were observed in the placebo group . CONCLUSIONS Both drugs tested intravenously were equally effective and safe for the rapid conversion of recent-onset atrial fibrillation to sinus rhythm . However , propafenone offered the advantage of more rapid conversion than amiodarone", "BACKGROUND The ideal management of patients with newly diagnosed symptomatic atrial fibrillation ( AF ) remains unknown . Current practice guidelines recommend a trial of antiarrhythmic drugs ( AAD ) prior to considering an invasive ablation procedure . However , earlier ablation offers an opportunity to halt the progressive patho-anatomical changes associated with AF , as well as impart other important clinical benefits . OBJECTIVE The aim of this study is to determine the optimal initial management strategy for patients with newly diagnosed , symptomatic atrial fibrillation . METHODS / DESIGN The EARLY-AF study ( Clinical Trials.govNCT02825979 ) is a prospect i ve , open label , multicenter , r and omized trial with a blinded assessment of outcomes . A total of 298 patients will be r and omized in a 1:1 fashion to first-line AAD therapy , or first-line cryoballoon-based pulmonary vein isolation . Patients with symptomatic treatment naïve AF will be included . Arrhythmia outcomes will be assessed by implantable cardiac monitor ( ICM ) . The primary outcome is time to first recurrence of AF , atrial flutter , or atrial tachycardia ( AF/AFL/AT ) between days 91 and 365 following AAD initiation or AF ablation . Secondary outcomes include arrhythmia burden , quality of life , and healthcare utilization . DISCUSSION The EARLY-AF study is a r and omized trial design ed to evaluate the optimal first management approach for patients with AF . We hypothesize that catheter ablation will be superior to drug therapy in prevention of AF recurrence", "Background : Atrial fibrillation is associated with increased risks of death , stroke/systemic embolism , and bleeding ( incurred by antithrombotic therapy ) , which may occur early after diagnosis . Methods : We assessed the risk of early events ( death , stroke/systemic embolism , and major bleeding ) over 12 months and their relation to the time after diagnosis of atrial fibrillation in 52 014 patients prospect ively enrolled in the GARFIELD-AF registry ( Global Anticoagulant Registry in the FIELD – Atrial Fibrillation ) between March 2010 and August 2016 . Results : Over 12 months , 2140 patients died ( mortality rate , 4.3 ; 95 % CI , 4.2–4.5 per 100 person-years ) , of whom 288 ( 13.5 % ) died in the first month ( 6.8 ; 95 % CI , 6.1–7.6 ) . Over 12 months , 657 patients had a stroke/systemic embolism ( 1.3 ; 95 % CI , 1.2–1.4 ) and 411 had a major bleeding ( 0.8 ; 95 % CI , 0.8–0.9 ) . During the first month , the rates ( per 100 person-years ) of stroke/systemic embolism and major bleed were 2.3 ( 95 % CI , 1.9–2.8 ) and 1.5 ( 95 % CI , 1.2–1.9 ) , respectively . The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality ( 3.5 ; 95 % CI , 3.0–4.1 ) , in particular , heart failure , sudden death , and acute coronary syndromes ( 1.0 [ 95 % CI , 0.8–1.4 ] , 0.6 [ 95 % CI , 0.4–0.8 ] , and 0.5 [ 95 % CI , 0.3–0.8 ] , respectively ) . Age , heart failure , prior stroke , history of cirrhosis , vascular disease , moderate-to-severe kidney disease , diabetes mellitus , and living in North or Latin America were independent predictors of a higher risk of early death , whereas anticoagulation and living in Europe or Asia were independent predictors of a lower risk of early death . A predictive model developed for the 1-month risk of death had a C-statistic of 0.81 ( 95 % CI , 0.78–0.83 ) . Conclusions : The increased hazard of early events , in particular , cardiovascular mortality , in newly diagnosed atrial fibrillation points to the importance of comprehensive care for such patients and should alert clinicians to detect warning signs of possible early mortality . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01090362", "BACKGROUND Although rhythm control has failed to demonstrate long-term benefits over rate control in longst and ing episodes of atrial fibrillation ( AF ) , there is little evidence concerning recent-onset ones . We analyzed the benefits of rhythm and rate control in terms of symptoms alleviation and need for hospital admission in patients with recent-onset AF . METHODS This was a multicenter , observational , cross-sectional study with prospect i ve st and ardized data collection carried out in 124 emergency departments ( EDs ) . Clinical variables , treatment effectiveness , and outcomes ( control of symptoms , final disposition ) were analyzed in stable patients with recent-onset AF consulting for AF-related symptoms . RESULTS Of 421 patients included , rhythm control was chosen in 352 patients ( 83.6 % ) , a global effectiveness of 84 % . Rate control was performed in 69 patients ( 16.4 % ) and was achieved in 67 ( 97 % ) of them . Control of symptoms was achieved in 396 ( 94.1 % ) patients and was associated with a heart rate after treatment ≤ 110 beats/min ( odds ratio [ OR ] = 14.346 , 95 % confidence interval [ CI ] = 3.90 to 52.70 , p a rhythm control strategy ( OR = 2.22 , 95 % CI = 1.20 - 4.60 , p = 0.031 ) and admission was associated with a heart rate > 110 beats/min after treatment ( OR = 29.71 , 95 % CI = 7.19 to 123.07 , p and acute heart failure ( OR = 9.45 , 95 % CI = 2.91 to 30.65 , p recent-onset AF patients in whom rhythm control was attempted in the ED had a high rate of symptoms ' alleviation and a reduced rate of hospital admissions", "BACKGROUND Patients with recent‐onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion . However , whether immediate restoration of sinus rhythm is necessary is not known , since atrial fibrillation often terminates spontaneously . METHODS In a multicenter , r and omized , open‐label , noninferiority trial , we r and omly assigned patients with hemodynamically stable , recent‐onset ( to be treated with a wait‐ and ‐see approach ( delayed‐cardioversion group ) or early cardioversion . The wait‐ and ‐see approach involved initial treatment with rate‐control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours . The primary end point was the presence of sinus rhythm at 4 weeks . Noninferiority would be shown if the lower limit of the 95 % confidence interval for the between‐group difference in the primary end point in percentage points was more than ‐10 . RESULTS The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients ( 91 % ) in the delayed‐cardioversion group and in 202 of 215 ( 94 % ) in the early‐cardioversion group ( between‐group difference , ‐2.9 percentage points ; 95 % confidence interval [ CI ] , ‐8.2 to 2.2 ; P=0.005 for noninferiority ) . In the delayed‐cardioversion group , conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients ( 69 % ) and after delayed cardioversion in 61 patients ( 28 % ) . In the early‐cardioversion group , conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients ( 16 % ) and after cardioversion in 171 patients ( 78 % ) . Among the patients who completed remote monitoring during 4 weeks of follow‐up , a recurrence of atrial fibrillation occurred in 49 of 164 patients ( 30 % ) in the delayed‐cardioversion group and in 50 of 171 ( 29 % ) in the early‐cardioversion group . Within 4 weeks after r and omization , cardiovascular complications occurred in 10 patients and 8 patients , respectively . CONCLUSIONS In patients presenting to the emergency department with recent‐onset , symptomatic atrial fibrillation , a wait‐ and ‐see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks . ( Funded by the Netherl and s Organization for Health Research and Development and others ; RACE 7 ACWAS Clinical Trials.gov number , NCT02248753 .", "Ranolazine , an antianginal agent with antiarrhythmic properties , prevents atrial fibrillation ( AF ) in patients with acute coronary syndrome . In experimental models , the combination of ranolazine and amiodarone has marked synergistic effects that potently suppress AF . Currently , the clinical effect of the ranolazine-amiodarone combination for the conversion of AF is unknown . This prospect i ve r and omized pilot study compared the safety and efficacy of ranolazine plus amiodarone versus amiodarone alone for the conversion of recent-onset AF . We enrolled 51 consecutive patients with AF ( were r and omized to intravenous amiodarone for 24 hours ( group A , n = 26 ) or to intravenous amiodarone plus oral ranolazine 1,500 mg at time of r and omization ( group A + R , n = 25 ) . The 2 groups were well balanced with respect to clinical characteristics and left atrial diameter . Conversion within 24 hours ( primary end point ) was achieved in 22 patients ( 88 % ) in group A + R versus 17 patients ( 65 % ) in group A ( p = 0.056 ) . Time to conversion was shorter in group A + R than in group A ( 9.8 ± 4.1 vs 14.6 ± 5.3 hours , p = 0.002 ) . According to Cox regression analysis , left atrial diameter and A + R treatment were the only independent predictors of time to conversion ( hazard ratio 5.35 , 95 % confidence interval 2.37 to 12.11 , p respectively ) . There were no proarrhythmic events in either group . In conclusion , addition of ranolazine to st and ard amiodarone therapy is equally safe and appears to be more effective compared to amiodarone alone for conversion of recent-onset AF " ]	41186d8c-06ff-11f0-808a-c43d1ab1c353
Background and Aims Probiotics was considered as a potential therapy for nonalcoholic fatty liver disease ( NAFLD ) without approval and comprehensive assessment in recent years , which call for a meta- analysis . Methods We performed electronic and manual search es including English and Chinese data bases published before April 2019 , with the use of mesh term and free text of " nonalcoholic fatty liver disease " and " probiotics . " Clinical trials evaluating the efficacy of probiotic therapy in NAFLD patients were included according to the eligibility criteria . With the use of r and om effects models , clinical outcomes were presented as weighted mean difference ( WMD ) with 95 % confidence interval ( CI ) , while heterogeneity and meta-regression were also assessed . Results 28 clinical trials enrolling 1555 criterion proven NAFLD patients with the use of probiotics from 4 to 28 weeks were included . Overall , probiotic therapy had beneficial effects on body mass index ( WMD : -1.46 , 95 % CI : [ -2.44 , -0.48 ] ) , alanine aminotransferase ( WMD : -13.40 , 95 % CI : [ -17.03 , -9.77 ] ) , aspartate transaminase ( WMD : -13.54 , 95 % CI : [ -17.86 , -9.22 ] ) , gamma-glutamyl transpeptidase ( WMD : -9.88 , 95 % CI : [ -17.77 , -1.99 ] ) , insulin ( WMD : -1.32 , 95 % CI : [ -2.43 , -0.21 ] ) , homeostasis model assessment -insulin resistance ( WMD : -0.42 , 95 % CI : [ -0.73 , -0.12 ] ) , and total cholesterol ( WMD : -15.38 , 95 % CI : [ -26.50 , -4.25 ] ) , but not in fasting blood sugar , lipid profiles , or tumor necrosis factor-alpha . Conclusion The systematic review and meta- analysis support that probiotics are superior to placebo in NAFLD patients and could be utilized as a common complementary therapeutic approach	[ "Background Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis ( NASH ) . Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota . Aims To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides ( Fos ) in the treatment of NASH . Methods A total of 66 patients were r and omly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification ( i.e. , diet and exercise ) versus lifestyle modification alone . The following variables were assessed at −4 ( beginning of the dietary lead-in period ) , 0 ( r and omization ) , 6 , 12 , 18 , and 24 weeks : aspartate transaminase ( AST ) , alanine transaminase ( ALT ) , bilirubin , albumin , total cholesterol , high-density lipoprotein ( HDL ) cholesterol , low-density lipoprotein ( LDL ) cholesterol , triglycerides , fasting plasma glucose , insulin , C-peptide , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment of insulin resistance ( HOMA-IR ) , and serum endotoxins . Liver biopsies were performed at entry and repeated after 24 weeks of treatment . Results At the end of study period , we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST −69.6 versus −45.9 IU/mL ( P LDL cholesterol −0.84 versus −0.18 mmol/L ( P ) , HOMA-IR −1.1 versus −0.6 ( P serum endotoxin −45.2 versus −30.6 pg/mL ( P steatosis ( P , and the NASH activity index ( P 0.05 ) . Conclusions Bifidobacterium longum with Fos and lifestyle modification , when compared to lifestyle modification alone , significantly reduces TNF-α , CRP , serum AST levels , HOMA-IR , serum endotoxin , steatosis , and the NASH activity index ", "BACKGROUND According to previous studies , probiotic and prebiotic supplementation have desirable effects on glycemic parameters . Thus far , the effect of supplementation on the glycemic parameters and adipokines in non-alcoholic fatty liver disease ( NAFLD ) has not been assessed . Therefore , the aim of this study was to determine the effects of supplementation with probiotic and prebiotic on adiokines and glycemic parameters in the patients with NAFLD . METHODS In the present r and omized , double-blind , placebo-controlled trial , 89 patients with NAFLD were r and omly divided into three groups to receive one probiotic capsule + 16 g/d maltodextrin ( probiotic group ) or 16 g/d oligofructose powder + one placebo capsule ( prebiotic group ) , and one placebo capsule + 16 g/d maltodextrin ( control group ) for 12 weeks . All the subjects in the study were advised to follow the weight loss diet and physical activity recommendations during the intervention . Fasting blood sample s were taken at baseline and after the intervention to measure leptin , adiponectin , insulin , and fasting blood sugar . RESULTS At the end of the study , serum concentrations of leptin , insulin , and HOMA-IR decreased significantly in the probiotic and prebiotic groups compared with the control group . Despite the changes within the groups , serum concentrations of adiponectin did not change significantly between the three groups . Also , fasting blood sugar did not change between the groups , but decreased in the prebiotic group . Quantitative insulin-sensitivity check index ( QUICKI ) increased significantly in probiotic and prebiotic groups compared with the control group . CONCLUSION Probiotic and prebiotic supplementation along with lifestyle intervention has a favorable impact on glycemic parameters and leptin levels compared with lifestyle intervention alone", "BACKGROUND Probiotics have a beneficial effect on nonalcoholic fatty liver disease ( NAFLD ) in animal models . R and omized placebo-controlled trials ( RCTs ) in NAFLD are still lacking in humans despite a large number of data from animal research . AIM We performed a double-blind single center RCT of live multi-strain probiotic vs. placebo in type 2 diabetes patients with NAFLD . METHODS A total of 58 patients met the criteria for inclusion . They were r and omly assigned to receive the multi-probiotic \" Symbiter \" ( concentrated biomass of 14 probiotic bacteria genera Bifidobacterium , Lactobacillus , Lactococcus , Propionibacterium ) or placebo for 8-weeks administered as a sachet formulation in double-blind treatment . The primary main outcomes were the changes in fatty liver index ( FLI ) and liver stiffness ( LS ) measured by Shear Wave Elastography ( SWE ) . Secondary outcomes were the changes in aminotransferase activity , serum lipids and cytokines ( TNF-α , IL-1β , IL-6 , IL-8 , and IFN-γ ) levels . Analysis of covariance was used to assess the difference between groups . RESULTS In the probiotic group , FLI significantly decreased from 84.33+/-2.23 to 78.73+/-2.58 ( p reduction of LS measured by SWE was detected . Analysis of the secondary outcomes showed that probiotics reduced the level of serum AST and GGT . Among the markers of chronic systemic inflammatory state , only TNF-α and IL-6 levels changed significantly after the treatment with the probiotic . CONCLUSION The probiotic \" Symbiter \" reduces liver fat , aminotransferase activity , and the TNF-α and IL-6 levels in NAFLD patients . Modulation of the gut microbiota might represent a new therapy for NAFLD , which should be tested in larger studies", "BACKGROUND Probiotics and prebiotics are considered to be beneficial to the gastrointestinal health of infants . OBJECTIVE The objective was to evaluate infant formulas containing probiotics and synbiotics ( combinations of probiotics and prebiotics ) for safety and tolerance . DESIGN In a prospect i ve , controlled , double-blind , r and omized trial , healthy full-term infants were exclusively fed a control formula or study formulas containing Bifidobacterium longum BL999 ( BL999 ) + Lactobacillus rhamnosus LPR ( LPR ) , BL999 + LPR + 4 g/L of 90 % galactooligosaccharide/10 % short-chain fructooligosaccharide ( GOS/SCFOS ) , or BL999 + Lactobacillus paracasei ST11 ( ST11 ) + 4 g/L GOS/SCFOS from . Safety and tolerance were assessed based on weight gain during the treatment period ( primary outcome ) as well as recumbent length , head circumference , digestive tolerance , and adverse events ( secondary outcomes ) , which were evaluated at 2 , 4 , 8 , 12 , 16 , and 52 wk of age . RESULTS Two hundred eighty-four infants were enrolled . During the treatment period , difference in mean weight gain between control and study formula groups in both the intention-to-treat and per- protocol population s were within the predefined equivalence boundaries of + /-3.9 g/d , indicating equivalent weight gain . Secondary outcomes did not show significant differences between groups during the treatment period . CONCLUSION Infants fed formulas containing probiotics or synbiotics show a similar rate in weight gain compared with those fed a control formula and tolerate these formulas well", "BACKGROUND Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of synbiotic has been proposed as an effective treatment of NAFLD because of its modulating effect on the gut flora , which can influence the gut-liver axis . OBJECTIVE The objective was to evaluate the effects of supplementation with synbiotic on hepatic fibrosis , liver enzymes , and inflammatory markers in patients with NAFLD . DESIGN In a r and omized , double-blind , placebo-controlled clinical trial conducted as a pilot study , 52 patients with NAFLD were supplemented twice daily for 28 wk with either a synbiotic or a placebo capsule . Both groups were advised to follow an energy-balanced diet and physical activity recommendations . RESULTS At the end of the study , the alanine aminotransferase ( ALT ) concentration decreased in both groups ; this reduction was significantly greater in the synbiotic group . At the end of the study , the following significant differences [ means ( 95 % CIs ) ] were seen between the synbiotic and placebo groups , respectively : ALT [ -25.1 ( -26.2 , -24 ) compared with -7.29 ( -9.5 , -5.1 ) IU/L ; P 0.001 ] , aspartate aminotransferase [ -31.33 ( -32.1 , -30.5 ) compared with -7.94 ( -11.1 , -4.8 ) IU/L ; P ] , γ-glutamyltransferase [ -15.08 ( -15.5 , -14.7 ) compared with -5.21 ( -6.6 , -3.9 ) IU/L ; P protein [ -2.3 ( -3 , -1.5 ) compared with -1.04 ( -1.5 , -0.6 ) mmol/L ; P 0.05 ] , tumor necrosis factor-α [ -1.4 ( -1.7 , -1.1 ) compared with -0.59 ( -0.8 , -0.3 ) mmol/L ; P p65 [ -0.016 ( -0.022 , -0.011 ) compared with 0.001 ( -0.004 , -0.007 ) mmol/L ; P score as determined by transient elastography [ - 2.98 ( -3.6 , -2.37 ) compared with -0.77 ( -1.32 , -0.22 ) kPa ; P CONCLUSIONS Synbiotic supplementation in addition to lifestyle modification is superior to lifestyle modification alone for the treatment of NAFLD , at least partially through attenuation of inflammatory markers in the body . Whether these effects will be sustained with longer treatment duration s remains to be determined", "Background : Non-alcoholic steatohepatitis ( NASH ) is a clinicopathological entity that is being recognized more frequently in recent years . This study aim ed to evaluate the effects of Metformin , with and without a probiotic supplement on liver aminotransferases in patients with NASH . Methods : Sixty four patients 18 - 75 years with NASH confirmed by biopsy and histological assessment were enrolled to study . Patients were r and omized to one of the following treatments for 6 months : Group I , probiotic ( Protexin two tablets per day ) plus Metformin 500 mg two tablets per day ( Met/Pro ) , or group II , Metformin 500 mg two tablets per day plus two placebo tablet ( Met/P ) . After 6 month alanine aminotransferase ( ALT ) , aspartate aminotransferase , and ultrasound grading of NASH were assessed . Results : In group I , serum alanine aminotransferase ( ALT : 133.7 ± 70 vs. 45.2 ± 32.5 ; P 0.00 ) , and aspartate aminotransferase activity ( AST : 123.1 ± 72 vs. 44.2 ± 33.9 ; P and ultrasound grading of NASH ( P while serum alanine aminotransferase ( ALT ) was not significantly reduced ( 118.4 ± 67.9 vs. 112.5 ± 68.7 ; P ( AST : 125.3 ± 71 vs. 113.4 ± 71 ; P did fall significantly ( P fell significantly in both groups . Conclusions : Probiotic combination with Metformin improves liver aminotransferases better than metformin alone in patients with NASH", "Nonalcoholic fatty liver disease is the most prevalent chronic liver disease in Western countries ; it can progress to nonalcoholic steatohepatitis ( NASH ) , cirrhosis and hepatocarcinoma . The importance of gut-liver-adipose tissue axis has become evident and treatments targeting gut microbiota may improve inflammatory and metabolic parameters in NASH patients . In a r and omized , controlled clinical trial , involving 50 biopsy-proven NASH patients , we investigated the effects of synbiotic supplementation on metabolic parameters , hepatic steatosis , intestinal permeability , small intestinal bacterial overgrowth ( SIBO ) and lipopolysaccharide ( LPS ) serum levels . Patients were separated into two groups receiving Lactobacillus reuteri with guar gum and inulin for three months and healthy balanced nutritional counseling versus nutritional counseling alone . Before and after the intervention we assessed steatosis by magnetic resonance imaging , intestinal permeability by lactulose/mannitol urinary excretion and SIBO by glucose breath testing . NASH patients presented high gut permeability , but low prevalence of SIBO . After the intervention , only the synbiotic group presented a reduction in steatosis , lost weight , diminished BMI and waist circumference measurement . Synbiotic did not improve intestinal permeability or LPS levels . We concluded that synbiotic supplementation associated with nutritional counseling seems superior to nutritional counseling alone for NASH treatment as it attenuates steatosis and may help to achieve weight loss", "ABSTRACT Developments in genome‐wide association studies and the increasing availability of summary genetic association data have made application of Mendelian r and omization relatively straightforward . However , obtaining reliable results from a Mendelian r and omization investigation remains problematic , as the conventional inverse‐variance weighted method only gives consistent estimates if all of the genetic variants in the analysis are valid instrumental variables . We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate . This estimator is consistent even when up to 50 % of the information comes from invalid instrumental variables . In a simulation analysis , it is shown to have better finite‐ sample Type 1 error rates than the inverse‐variance weighted method , and is complementary to the recently proposed MR‐Egger ( Mendelian r and omization‐Egger ) regression method . In analyses of the causal effects of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol on coronary artery disease risk , the inverse‐variance weighted method suggests a causal effect of both lipid fractions , whereas the weighted median and MR‐Egger regression methods suggest a None effect of high‐density lipoprotein cholesterol that corresponds with the experimental evidence . Both median‐based and MR‐Egger regression methods should be considered as sensitivity analyses for Mendelian r and omization investigations with multiple genetic variants", "The aim of this study was to evaluate the effect of a synbiotic containing Lactobacillus acidophilus ATCC 4962 , fructooligosaccharide , inulin and mannitol on plasma lipid profiles and erythrocyte membrane properties in hypercholesterolaemic pigs on high- and low-fat diets . Twenty-four white male L and race pigs were r and omly allocated to four treatment groups for 8 weeks ( n 6 ) . Treatment factors were the supplementation of synbiotic ( with and without ) and dietary fat ( 5 and 15 % ) . The supplementation of synbiotic reduced plasma total cholesterol ( P = 0.001 ) , TAG ( P = 0.002 ) and LDL-cholesterol ( P = 0.045 ) for both dietary fats . A higher concentration of esterified-cholesterol in HDL of pigs supplemented with synbiotic than the control regardless of dietary fat ( P = 0.036 ) indicated that cholesterol was reduced in the form of cholesteryl esters . Reduced concentration of cholesteryl esters ( P concentration of TAG ( P = 0.042 ) in LDL of pigs on synbiotic suggested that LDL-cholesterol was reduced via the hydrolysis of smaller and denser LDL particles . The erythrocytes of pigs without any synbiotic showed more prevalence of spur cells than those given the synbiotic , as supported by the higher cholesterol : phospholipid ratio in erythrocytes ( P = 0.001 ) . Also , membrane fluidity and rigidity were improved as supported by the decreased fluorescence anisotropies in the Hb-free erythrocyte membrane of pigs given synbiotic ( P synbiotic reduced plasma TAG , total cholesterol and LDL-cholesterol in hypercholesterolaemic pigs , possibly in the form of cholesteryl esters , via the interrelated pathways of lipid transporters ( VLDL , LDL and HDL ) . The synbiotic also reduced deformation of erythrocytes via improved membrane fluidity and permeability", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Objectives : The purpose of this study was to investigate whether probiotics had an effect on proinflammatory markers and cytokines in overweight and obese individuals and whether they could have synergistic effects with weight-loss diets . Methods : A total of 75 healthy overweight and obese individuals completed this r and omized doubled-blind controlled clinical trial . Participants were r and omly assigned to groups consuming regular yogurt with a low-calorie diet ( LCD , RLCD ; n = 25 ) or receiving probiotic yogurt with LCD ( PLCD ; n = 25 ) or consuming probiotic yogurt without LCD ( PWLCD ; n = 25 ) for 8 weeks . The pribiotic regimen contained 200 g/day yogurt , enriched by Lactobacillus acidophilus La5 , Bifidobacterium BB12 , and Lactobacillus casei DN001 108 colony-forming units/g . Body fat percentage , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor-alpha ( TNF-α ) , leptin , and mRNA levels of inflammation-related genes ( TNF-α and RAR-related orphan receptor gamma [ ROR-γt ] ) in peripheral blood mononuclear cells ( P BMC s ) were measured . Results : A reduction in body mass index ( BMI ) , fat percentage , and leptin level was observed that was more obvious in groups who received the weight-loss diet with probiotic yogurt . Reduction in the gene expression of ROR-γt was significant in the PLCD group ( p The expression of TNF-α did not change among all groups after intervention . The mean concentration of leptin was significantly decreased in all groups after the dietary intervention , but the mean changes in leptin level in the PLCD group was more prominent compared to the other two groups ( −2.38 , p The reduction in serum levels of hs-CRP was more evident in the PWLCD group compared to the PLCD and RLCD groups after the 8-week intervention ( −3.4 , p = 0.03 vs −1.76 , p the weight-loss diet and probiotic yogurt had synergistic effects on T-cells subset specific gene expression in P BMC s , fat percentage , and body weight among overweight and obese individuals", "Background . Ectopic fat deposition in the pancreas and its relationship with hepatic steatosis and insulin resistance have not been compared between patients with nonalcoholic fatty liver disease ( NAFLD ) and healthy controls . Aim . Using a novel magnetic resonance imaging ( MRI ) based biomarker , the proton-density-fat-fraction ( MRI-PDFF ) , we compared pancreatic fat content in patients with biopsy-proven NAFLD to healthy controls and determined whether it is associated with insulin resistance and liver fat content . Methods . This nested case-control study was derived from two prospect i ve studies including 43 patients with biopsy-proven NAFLD and 49 healthy controls who underwent biochemical testing and MRI . Results . Compared to healthy controls , patients with NAFLD had significantly higher pancreatic MRI-PDFF ( 3.6 % versus 8.5 % , P value hepatic and pancreatic MRI-PDFF ( Spearman correlation , P = 0.57 , P value insulin resistance determined by homeostatic-model-of-insulin-resistance ( HOMA-IR ) greater than 2.5 had higher pancreatic ( 7.3 % versus 4.5 % , P value = 0.015 ) and liver ( 13.5 % versus 4.0 % , P value MRI-PDFF . Conclusion . Patients with NAFLD have greater pancreatic fat than normal controls . Insulin resistance is associated with liver and pancreatic fat accumulation", "Background : Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Oral administration of symbiotic and Vitamin E has been proposed as an effective treatment in NAFLD patients . This study was carried out to assess the effects of symbiotic and /or Vitamin E supplementation on liver enzymes , leptin , lipid profile , and some parameters of insulin resistance ( IR ) in NAFLD patients . Material s and Methods : We r and omly assigned sixty NAFLD adult patients to receive ( 1 ) symbiotic twice daily + Vitamin E-like placebo capsule ; ( 2 ) 400 IU/d Vitamin E + symbiotic-like placebo ; ( 3 ) symbiotic twice daily + 400 IU/d Vitamin E ; and ( 4 ) symbiotic-like placebo + Vitamin E-like placebo for 8 weeks . Results : Symbiotic plus Vitamin E supplementation led to a significant decrease in concentrations of liver transaminase ( P ≤ 0.05 ) . Mean difference of apolipoprotein A-1 was more significant in symbiotic group compared to control . However , mean difference of apolipoprotein B100/A-1 was only significant in symbiotic group compared to control . At the end of the study , significant differences in total cholesterol ( TC ) and low-density lipoprotein cholesterol ( LDL-C ) were seen between the symbiotic plus Vitamin E and control groups ( P of symbiotic plus Vitamin E supplements led to a significant decrease in concentrations of triglycerides ( TG ) after the intervention . Significant differences in leptin , fasting blood sugar ( FBS ) , and insulin levels were seen between the symbiotic plus Vitamin E and control groups at the end of the study ( P contrast , symbiotic and /or Vitamin E supplementation did not affect high-density lipoprotein cholesterol and homeostasis model assessment for IR levels . Conclusion : In our study , symbiotic plus Vitamin E supplementation was the most effective treatment in lowering liver enzymes , leptin , FBS , insulin , TG , TC , and LDL-C among NAFLD patients", "BACKGROUND Probiotics have profound effect on nonalcoholic steatohepatitis ( NASH ) in animal models . We aim ed to test the hypothesis that probiotics treatment was superior to usual care in reducing liver fat in NASH patients . MATERIAL AND METHODS Patients with histology-proven NASH were r and omized to receive probiotics ( n = 10 ) or usual care ( n = 10 ) for 6 months . The Lepicol probiotic formula contained Lactobacillus plantarum , Lactobacillus deslbrueckii , Lactobacillus acidophilus , Lactobacillus rhamnosus and Bifidobacterium bifidum . The primary endpoint was change in intrahepatic triglyceride content ( IHTG ) , as measured by proton-magnetic resonance spectroscopy , from baseline to month 6 . Secondary endpoints included changes in liver biochemistry and metabolic profile . RESULTS IHTG decreased from 22.6 ± 8.2 % to 14.9 ± 7.0 % in the probiotic group ( P = 0.034 ) but remained static in the usual care group ( 16.9 ± 6.1 % to 16.0 ± 6.6 % ; P = 0.55 ) . Six subjects in the probiotic group had IHTG reduced by more than 30 % from baseline , compared to 2 subjects in the usual care group ( P = 0.17 ) . The probiotic group also had greater reduction in serum aspartate aminotransferase level ( P = 0.008 ) . On the other h and , the use of probiotics was not associated with changes in body mass index , waist circumference , glucose and lipid levels . CONCLUSIONS Probiotics treatment may reduce liver fat and AST level in NASH patients . The therapeutic potential of probiotics in NASH should be tested in larger studies", "OBJECTIVE The present pilot trial was carried out to evaluate the effects of an acute treatment with a mixture containing 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus per day in patients with non alcoholic fatty liver disease ( NAFLD ) . RESEARCH METHODS A sample of 30 patients with NAFLD ( diagnosed by liver biopsy ) was enrolled and 28 patients were analyzed in a double blind r and omized clinical trial . Patients were r and omized to one of the following treatments during 3 months : group I , treated with one tablet per day with 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus and group II , treated with one placebo tablet ( 120 mg of starch ) . RESULTS In group I , alanine amino transferase ( ALT : 67.7 + /- 25.1 vs. 60.4 + /- 30.4 UI/L ; p aspartate aminotransferase activity ( AST : 41.3 + /- 15.5 vs. 35.6 + /- 10.4 UI/L ; p gammaglutamine transferase levels ( gammaGT : 118.2 + /- 63.1 vs. 107.7 + /- 60.8 UI/L ; p liver function parameters remained unchanged ( ALT : 60.7 + /- 32.1 vs. 64.8 + /- 35.5 UI/L ; p aspartate aminotransferase activity ( AST : 31.7 + /- 13.1 vs. 36.4 + /- 13.8 UI/L ; ns ) and gammaglutamine transferase levels ( gammaGT : 82.1 + /- 55.1 vs. 83.6 + /- 65.3 UI/L ; ns ) . Anthropometric parameters and cardiovascular risk factors remained unchanged after treatment in both groups . CONCLUSION A tablet of 500 million of Lactobacillus bulgaricus and Streptococcus thermophilus , with a r and omized clinical design , improved liver aminotransferases levels in patients with NAFLD", "Background : Regarding to the growing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , concentrating on various strategies to its prevention and management seems necessary . The aim of this study was to determine the effects of symbiotic on C-reactive protein ( CRP ) , liver enzymes , and ultrasound findings in patients with NAFLD . Methods : Eighty NAFLD patients were enrolled in this r and omized , double-blind , placebo-controlled clinical trial . Participants received symbiotic in form of a 500 mg capsule ( containing seven species of probiotic bacteria and fructooligosaccharides ) or a placebo capsule daily for 8 weeks . Ultrasound grading , CRP , and liver enzymes were evaluated at the baseline and the end of the study . Results : In the symbiotic group , ultrasound grade decreased significantly compared to baseline ( P symbiotic supplementation was not associated with changes in alanine aminotransferase ( ALT ) and aspartate transaminase ( AST ) levels . In the placebo group , there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased ( P = 0.002 , P = 0.02 , respectively ) . CRP values remained static in either group . Conclusions : Symbiotic supplementation improved steatosis in NAFLD patients and might be useful in the management of NAFLD or protective against its progression", "Objective : Nonalcoholic fatty liver disease ( NAFLD ) is a condition defined by exceeding triglycerides accumulation in the liver . The condition can develop into fibrosis , cirrhosis , and hepatocellular carcinoma . Considering the ever-increasing prevalence of NAFLD , the aim of the present study was to investigate the effects of probiotic supplementation on glycemic and inflammatory indices in patients with NAFLD . Methods : This r and omized clinical trial was conducted on 42 patients with NAFLD who had been referred to a gastroenterology clinic . Subjects in the intervention and control groups consumed 2 capsules/day probiotic or placebo , respectively , for 8 weeks . Fasting blood sugar ( FBS ) , insulin , insulin resistance , tumor necrosis factor alpha ( TNF-α ) , and interleukin 6 ( IL-6 ) were measured at baseline and at the end of the study . Results : Means of FBS , insulin , insulin resistance , and IL-6 were significantly different between groups after intervention ( p 0.05 ) . In the probiotic group , insulin , insulin resistance , TNF-α , and IL-6 decreased significantly at the end of the study compared to the beginning of study . Conclusion : Considering the effects of probiotic supplementation on the reduction of glycemic and inflammatory indices in patients with NAFLD , consumption of probiotics is recommended as a complementary therapy in these patients", "Objectives : This study aims to evaluate the effects of some probiotics on sonographic and biochemical nonalcoholic fatty liver disease ( NAFLD ) . Methods : This r and omized triple-blind trial was conducted among 64 obese children with sonographic NAFLD . They were r and omly allocated to receive probiotic capsule ( containing Lactobacillus acidophilus ATCC B3208 , 3 × 109 colony forming units [ CFU ] ; Bifidobacterium lactis DSMZ 32269 , 6 × 109 CFU ; Bifidobacterium bifidum ATCC SD6576 , 2 × 109 CFU ; Lactobacillus rhamnosus DSMZ 21690 , 2 × 109 CFU ) or placebo for 12 weeks . Results : After intervention , in the probiotic group the mean levels of alanine aminotransferase decreased from 32.8 ( 19.6 ) to 23.1 ( 9.9 ) U/L ( P = 0.02 ) and mean aspartate aminotransferase decreased from 32.2 ( 15.7 ) to 24.3 ( 7.7 ) U/L ( P = 0.02 ) . Likewise the mean cholesterol , low-density lipoprotein-C , and triglycerides as well as waist circumference decreased in the intervention group , without significant change in weight , body mass index , and body mass index z score . After the trial , normal liver sonography was reported in 17 ( 53.1 % ) and 5 ( 16.5 % ) of patients in the intervention and placebo groups , respectively . Conclusions : The present findings suggest that a course of the abovementioned probiotic compound can be effective in improving pediatric NAFLD", "Gut microbiota modifiers may have beneficial effects of non‐alcoholic fatty liver disease ( NAFLD ) but r and omised controlled trials ( RCT ) are lacking in children ", "Although non-alcoholic fatty liver disease ( NAFLD ) is the leading aetiology of liver disorders in the world , there is no proven treatment for NAFLD patients with normal or low BMI . The aim of this study was to evaluate the efficacy of synbiotics supplementation in NAFLD patients with normal or low BMI . In this r and omised , double-blind , placebo-controlled , clinical trial , fifty patients with NAFLD were assigned to take either a synbiotic supplement or a placebo capsule for 28 weeks . Both groups were advised to follow a healthy lifestyle . At the end of the study , hepatic steatosis and fibrosis reduced in both groups ; however , the mean reduction was significantly greater in the synbiotic group rather than in the placebo group ( P Furthermore , serum levels of fasting blood sugar , TAG and most of the inflammatory mediators reduced in the synbiotic group significantly compared with the placebo group ( P that synbiotic supplementation improves the main features of NAFLD in patients with normal and low BMI , at least partially through reduction in inflammatory indices . Further studies are needed to address the exact mechanism of action of these effects", "Background Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in developed and developing countries . The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD . Objective We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers , adipokine concentration , and gut peptide concentration as secondary outcomes in patients with NAFLD . Methods In this 24-wk , open-label , r and omized controlled clinical trial , 102 patients [ 50 men and 52 women ; mean age : 40 y ; body mass index ( in kg/m2 ) ( mean ± SD ) : 31.2 ± 4.9 ] were r and omly assigned to 3 groups , including 2 intervention groups and 1 control group . The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle ( i.e. , diet and exercise ) . The control group was advised to follow a healthy lifestyle alone . We evaluated differences between groups in liver function measures by using repeated- measures ANOVA , ANCOVA , and logistic regression . Results At the end of the study , the grade s of NAFLD , as determined by ultrasonography , showed a significant decrease in the synbiotic group compared with the conventional and control groups ( P respectively : serum concentration of alanine aminotransferase ( -14.5 ± 15.6 compared with 4.6 ± 15.4 and 3.1 ± 14.4 IU/L ; P = 0.008 ) , aspartate aminotransferase ( -7.5 ± 6.1 compared with 3.0 ± 8.2 and 3.1 ± 5.7 IU/L ; P ) , alkaline phosphatase ( -26.2 ± 16.8 compared with 3.4 ± 30.1 and 1.5 ± 31.9 IU/L ; P = 0.024 ) , and γ-glutamyltransferase ( -6.0 ± 6.0 compared with 1.0 ± 6.4 and 7.6 ± 11.4 IU/L ; P ) . Conclusion Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD . This trial was registered at the Iranian Registry of Clinical Trials website ( www.i rct .ir ) as I RCT 2017020932417N2", "The intestinal microbiota is closely associated with the development of obesity and nonalcoholic fatty liver disease ( NAFLD ) . This study investigated the effects of probiotic treatment on visceral fat area ( VFA ) and intrahepatic fat ( IHF ) fraction in NAFLD . Sixty-eight obese NAFLD patients ( > 5 % proton density fat fraction [ PDFF ] on magnetic resonance imaging [ MRI ] ) were r and omized to probiotic and placebo groups for 12 weeks . The probiotic mixture included 6 bacterial species . VFA and IHF were measured using the MRI-PDFF technique . Body weight and total body fat were reduced in the probiotic group but not in the placebo group . The mean IHF fraction was reduced after 12 weeks of treatment in the probiotic group compared to that at baseline ( from 16.3 ± 15.0 % to 14.1 ± 7.7 % , p = 0.032 ) but was not reduced in the placebo group . The decrease in IHF ( mean difference : −2.61 % , p = 0.012 ) was also greater in the probiotic group than in the placebo group . Reduction of triglyceride was greater in the probiotic treatment group than in the placebo group ( mean difference : −34.0 mg/dl , p = 0.0033 ) . However , the changes in IHF percentage and triglyceride levels were not different between placebo and control groups after adjusting for changes in body weight . Treatment with probiotics for 12 weeks result ed in significant reduction in IHF and body weight in obese NAFLD patients" ]	41186dd2-06ff-11f0-808a-c43d1ab1c353
The aim of this study is to gather evidence of head-to-head double-blind r and omized-controlled trials on the efficacy and safety of available treatments for attention deficit hyperactivity disorder ( ADHD ) in children and adolescents . A systematic review was conducted by two independent review ers in ten electronic data bases ( PROSPERO register CRD42016043239 ) . Method ological quality of included studies was evaluated according to the Jadad scale . Network meta-analyses were performed including double-blinded head-to-head trials comparing active allopathic drugs in patients ( 0–18 years old ) diagnosed with ADHD . The results of efficacy and safety of atomoxetine ( ATX ) , bupropion , buspirone ( BSP ) , dexamphetamine , edivoxetine ( EDX ) , guanfacine ( GXR ) , lisdexamfetamine ( LDX ) , methylpheni date ( MPH ) , mixed amphetamine salts , modafinil , pindolol ( PDL ) , reboxetine ( RBX ) , selegiline , and venlafaxine were analyzed using ADDIS software v.1.16.5 . Forty-eight trials were identified ( n = 4169 participants ) , of which 12 were used for efficacy analysis and 33 for safety analysis . On the CGI-I scale , the analysis revealed that MPH was more effective than ATX and GXR . For the safety outcomes , according to drug ranks , LDX was more likely to cause sleep disorders ( 39 % ) as well as loss of appetite ( 65 % ) and behavior problems such as irritability ( 60 % ) . BSP ( 71 % ) and EDX ( 44 % ) caused less appetite decrease . For behavioral effects , PDL was considered safest ( 50 % ) . For any adverse events , RBX ( 89 % ) was the safest alternative . The lack of head-to-head trials properly reporting outcomes of interest limited some comparisons . Network meta- analysis offered a broader overview on the available treatments for ADHD , especially for safety issues , and contributes towards evidence gathering and clinical practice decisions . A core outcome set for ADHD should be design ed to guide the conduction and report of clinical trials	[ "OBJECTIVE To compare methylpheni date ( MPH ) and dexamphetamine ( DEX ) in a sample of children with attention deficit hyperactivity disorder ( ADHD ) . METHOD A total of 125 children with ADHD received both MPH ( 0.3 mg/kg twice daily ) and DEX ( 0.15 mg/kg twice daily ) for 2 weeks a double-blind , crossover study . Outcome measures were Conners ' Parent Rating Scale-Revised , Conners ' Teacher Rating Scale-Revised , a Parent Global Perceptions question naire , the Continuous Performance Test , and the Barkley Side Effects Rating Scale . RESULTS There were significant group mean improvements from baseline score on all measures for both stimulants . On the Conners ' Teacher Rating Scale-Revised , response was greater on MPH than DEX on the conduct problems and hyperactivity factors , as well as on the hyperactivity index . On the Conners ' Parent Rating Scale-Revised , anxiety was the only factor to differ significantly , in favor of MPH . Parents rated 73 % of subjects as globally improved on MPH and 69 % improved on DEX , compared with baseline . Overall , 46 % of parents chose MPH as the preferred drug , compared with 37 % who chose DEX . On the Continuous Performance Test , there was no difference in the number of correct responses or errors between the two drugs . CONCLUSIONS Most children with ADHD improve significantly on both MPH and DEX . There was a slight advantage to MPH on most measures", "Objective : Attention-deficit/hyperactivity disorder ( ADHD ) is the most common neurobehavioral disorder of childhood . Principal treatment options for ADHD today include the psychostimulants , mainly methylpheni date ( MPH ) . However , approximately 30 % to 50 % of children and adults with ADHD either do not respond to or do not tolerate treatment with stimulants . In this 8-week open-label , MPH-controlled , parallel group design study , we investigate the efficacy of reboxetine , a new selective norepinephrine reuptake inhibitor , in the treatment of boys with ADHD with a history of intolerance to MPH therapy . Method : Twenty-seven outpatient boys , aged 6 to 16 years , diagnosed with ADHD , participated in the study . Those with a history of intolerance to MPH therapy were assigned to treatment with reboxetine ( 2 - 8 mg/d ) , and the rest were assigned to treatment with MPH ( 10 - 20 mg/d ) as the control group . The primary outcome measure for this study was the change in rating scores on the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , ADHD Scale ( DAS ) that was assessed at baseline and at 8 weeks . Results : At the end of 8 weeks , both reboxetine and MPH treatment regimens result ed in significant improvement in ADHD symptoms . The change in the reduction in the total DAS score and the DAS subscale scores between the reboxetine group and the MPH group was not statistically significant in any of the scores . Conclusions : Although preliminary , results of this study indicate that the use of reboxetine , a new selective norepinephrine reuptake inhibitor , in the treatment of ADHD could increase treatment options available for children who have shown intolerance or who are unresponsive to MPH", "Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind , placebo-controlled , crossover evaluation of the efficacy of st and ard methylpheni date twice a day and comparable doses every morning of a sustained-release preparation of methylpheni date ( SR-20 Ritalin ) , a sustained-release form of dextroamphetamine ( Dexedrine Spansule ) , and pemoline . The children were participating in a summer treatment program in which they engaged in recreational and classroom activities . Dependent measures include evaluations of social behavior during group recreational activities , classroom performance , and performance on a continuous performance task . Results revealed generally equivalent and beneficial effects of all four medications . Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication . The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion , and the effects lasted for 9 hours . The implication s of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed", "Objectives The aim of this study was to compare the efficacy and safety of the prodrug psychostimulant lisdexamfetamine dimesylate ( LDX ) and the non-stimulant noradrenergic compound atomoxetine ( ATX ) in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) who had previously responded inadequately to methylpheni date ( MPH ) . Methods This 9-week , head-to-head , r and omized , double-blind , active-controlled study ( SPD489 - 317 ; Clinical Trials.gov NCT01106430 ) enrolled patients ( aged 6–17 years ) with at least moderately symptomatic ADHD and an inadequate response to previous MPH therapy . Patients were r and omized ( 1:1 ) to an optimized daily dose of LDX ( 30 , 50 or 70 mg ) or ATX ( patients was time ( days ) to first clinical response . Clinical response was defined as a Clinical Global Impressions-Improvement ( CGI-I ) score of 1 ( very much improved ) or 2 ( much improved ) . Secondary efficacy outcomes included the proportion of responders at each study visit and the change from baseline in ADHD Rating Scale ( ADHD-RS-IV ) and CGI-Severity scores . Tolerability and safety were assessed by monitoring treatment-emergent adverse events ( TEAEs ) , height and weight , vital signs and electrocardiogram parameters . Endpoint was defined as the last post-baseline , on-treatment visit with a valid assessment . Results Of 267 patients r and omized ( LDX , n = 133 ; ATX , n = 134 ) , 200 ( 74.9 % ) completed the study . The median time to first clinical response [ 95 % confidence interval ( CI ) ] was significantly shorter for patients receiving LDX [ 12.0 days ( 8.0–16.0 ) ] than for those receiving ATX [ 21.0 days ( 15.0–23.0 ) ] ( p = 0.001 ) . By week 9 , 81.7 % ( 95 % CI 75.0–88.5 ) of patients receiving LDX had responded to treatment compared with 63.6 % ( 95 % CI 55.4–71.8 ) of those receiving ATX ( p = 0.001 ) . Also by week 9 , the difference between LDX and ATX in least-squares mean change from baseline ( 95 % CI ) was significant in favour of LDX for the ADHD-RS-IV total score [ −6.5 ( −9.3 to −3.6 ) ; p 0.56 ] , inattentiveness subscale score [ −3.4 ( −4.9 to −1.8 ) ; p 0.53 ] and the hyperactivity/impulsivity subscale score [ −3.2 ( −4.6 to −1.7 ) ; p mean ( st and ard deviation ) increases in systolic blood pressure [ LDX , + 0.7 mmHg ( 9.08 ) ; ATX , + 0.6 mmHg ( 7.96 ) ] , diastolic blood pressure [ LDX , + 0.1 mmHg ( 8.33 ) ; ATX , + 1.3 mmHg ( 8.24 ) ] and pulse rate [ LDX , + 3.6 bpm ( 10.49 ) ; ATX , + 3.7 bpm ( 10.75 ) ] , and decreases in weight [ LDX , −1.30 kg ( 1.806 ) ; ATX , −0.15 kg ( 1.434 ) ] . Conclusions LDX was associated with a faster and more robust treatment response than ATX in children and adolescents with at least moderately symptomatic ADHD who had previously responded inadequately to MPH . Both treatments displayed safety profiles consistent with findings from previous clinical trials", "This study evaluated the efficacy and safety of lisdexamfetamine dimesylate ( LDX ) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) in Europe . Osmotic-release oral system methylpheni date ( OROS-MPH ) was included as a reference arm . Patients ( 6 - 17 years old ) with a baseline ADHD Rating Scale version IV ( ADHD-RS-IV ) total score ≥ 28 were r and omized ( 1:1:1 ) to dose-optimized LDX ( 30 , 50 , or 70 mg/day ) , OROS-MPH ( 18 , 36 , or 54 mg/day ) or placebo for 7 weeks . Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement ( CGI-I ) rating , respectively . Safety assessment s included treatment-emergent adverse events ( TEAEs ) , electrocardiograms , and vital signs . Of 336 patients r and omized , 196 completed the study . The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 ( 95 % confidence interval [ CI ] : -21.5 to -15.7 ) ( p between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 ( 95 % CI : -15.9 to -10.2 ) ( p showing improvement ( CGI-I of 1 or 2 ) at endpoint were 78 % ( 70 - 86 ) , 14 % ( 8 - 21 ) , and 61 % ( 51 - 70 ) for LDX , placebo , and OROS-MPH . The most common TEAEs for LDX were decreased appetite , headache , and insomnia . Mean changes in vital signs were modest and consistent with the known profile of LDX . LDX was effective and generally well tolerated in children and adolescents with ADHD", "The efficacy and side effects of buspirone compared with methylpheni date ( MPH ) in the treatment of children with attention-deficit/hyperactivity disorder ( ADHD ) . A total of 34 children with ADHD as defined by DSM-IV-TR were r and omized to buspirone or methylpheni date dosed on weight-adjusted basis at buspirone ( 0.5 mg/kg/day ) and methylpheni date ( 0.3–1 mg/kg/day ) for a 6-week double-blind clinical trial . The principle measures of outcome were the teacher and parent ADHD Rating Scale . The side effects were assessed by the special side effect checklist of each drug . In both groups , the scores of teacher and parent ADHD Rating Scale significantly declined on the 6th week as compared to baseline ( p = 0.001 ) . These effects were observed in the subscales too . No significant differences were observed between the two protocol s on the total scores of parent and teacher ADHD Rating Scale , but methylpheni date was superior to buspirone in decreasing the symptoms of inattention . The side effects of buspirone were mild and rare in comparison with MPH . Buspirone has a favorable side-effects profile . It also has clinical ly and statistically significant impacts on improving the ADHD symptoms in children . These preliminary findings of the efficacy of buspirone in children with ADHD need large and cross-over studies", "Attention-deficit/hyperactivity disorder ( ADHD ) is associated with functional impairments in multiple domains of patients ’ lives . A secondary objective of this r and omized , active-controlled , head-to-head , double-blind , dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate ( LDX ) and atomoxetine ( ATX ) on functional impairment in children and adolescents with ADHD . Patients aged 6–17 years with an ADHD Rating Scale IV total score ≥28 and an inadequate response to methylpheni date treatment ( judged by investigators ) were r and omized ( 1:1 ) to once-daily LDX or ATX for 9 weeks . Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report ( WFIRS-P ) at baseline and at week 9 or early termination . p values were nominal and not corrected for multiple comparisons . Of 267 r and omized patients , 200 completed the study ( LDX 99 , ATX 101 ) . At baseline , mean WFIRS-P total score in the LDX group was 0.95 [ st and ard deviation ( SD ) 0.474 ; 95 % confidence interval ( CI ) 0.87 , 1.03 ] and in the ATX group was 0.91 ( 0.513 ; 0.82 , 1.00 ) . Scores in all WFIRS-P domains improved from baseline to endpoint in both groups , with least-squares mean changes in total score of −0.35 ( 95 % CI −0.42 , −0.29 ) for LDX and −0.27 ( −0.33 , −0.20 ) for ATX . The difference between LDX and ATX was statistically significant ( p for the Learning and School ( effect size of LDX vs ATX , 0.43 ) and Social Activities ( 0.34 ) domains and for total score ( 0.27 ) . Both treatments reduced functional impairment in children and adolescents with ADHD ; LDX was statistically significantly more effective than ATX in two of six domains and in total score ", "Lisdexamfetamine dimesylate ( LDX ) is a long-acting , prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder ( ADHD ) . This r and omized placebo-controlled trial of an optimized daily dose of LDX ( 30 , 50 or 70 mg ) was conducted in children and adolescents ( aged 6–17 years ) with ADHD . To evaluate the efficacy of LDX throughout the day , symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners ’ Parent Rating Scale-Revised ( CPRS-R ) at 1000 , 1400 and 1800 hours following early morning dosing ( 0700 hours ) . Osmotic-release oral system methylpheni date ( OROS-MPH ) was included as a reference treatment , but the study was not design ed to support a statistical comparison between LDX and OROS-MPH . The full analysis set comprised 317 patients ( LDX , n = 104 ; placebo , n = 106 ; OROS-MPH , n = 107 ) . At baseline , CPRS-R total scores were similar across treatment groups . At endpoint , differences ( active treatment − placebo ) in least squares ( LS ) mean change from baseline CPRS-R total scores were statistically significant ( P for LDX ( effect sizes : 1000 hours , 1.42 ; 1400 hours , 1.41 ; 1800 hours , 1.30 ) and OROS-MPH ( effect sizes : 1000 hours , 1.04 ; 1400 hours , 0.98 ; 1800 hours , 0.92 ) . Differences in LS mean change from baseline to endpoint were statistically significant ( P treatments in all four subscales of the CPRS-R ( ADHD index , oppositional , hyperactivity and cognitive ) . In conclusion , improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening ( 1800 hours )", "Objective . Very little research has focused on the efficacy of Adderall ( Shire-Richwood Inc , Florence , KY ) in the treatment of children with attention-deficit/hyperactivity disorder ( ADHD ) , and no studies have compared it with st and ardized doses of Ritalin ( Novartis Pharmaceuticals , East Hanover , NJ ) . It is thought that Adderall has a longer half-life than Ritalin and might minimize the loss of efficacy that occurs 4 or 5 hours after Ritalin ingestion . We compared two doses of Ritalin and Adderall in the treatment of ADHD in children in an acute study and assessed the medications ' time courses . Design . Within-subject , double-blind , placebo-controlled , crossover design lasting 6 weeks . As in our previous work , medication changes occurred on a daily basis in r and om order over days . Setting . Eight-week , weekday ( 9 hours daily ) summer treatment program at the State University of New York at Buffalo , using an intensive behavioral treatment program including a point system and parent training . Study Participants . Twenty-five children ( 21 boys and 4 girls ) diagnosed as ADHD using st and ardized structured interview and rating scales , mean age 9.6 years , 88 % Caucasian , of average intelligence , with no medical conditions that would preclude a trial of stimulant medication . Thirteen were comorbid for opposi-tional-defiant disorder and another 8 for conduct disorder . Interventions . Children received 10 mg of Ritalin , 17.5 mg of Ritalin , 7.5 mg of Adderall , 12.5 mg of Adderall , or placebo , twice a day ( 7:45 am and 12:15 pm ) , in r and om order with conditions changing daily for 24 days . Outcome Measures . Daily rates of behaviors in recreational and classroom setting s , and st and ardized ratings from counselors , teachers , and parents , were averaged across days within condition within child and compared . Within-subject relative sizes of the medication effects were computed by taking the placebo-minus-drug mean difference divided by the placebo st and ard deviation for each child , and were compared hourly between first daily ingestion ( 7:45am ) and 5:00 pm to assess the time course of the two drugs . Measures were taken at 12:00 pm ( recess rule violations ) and at 5:00 pm ( parent behavior ratings ) to determine whether Adderall was still effective at times when the effects of Ritalin should have worn off . Parent ratings were also made for evening behavior to assess possible rebound , and side effects ratings were obtained from parents , counselors , and teachers . Parents , counselors , and teachers also rated their perceptions of medication status and whether they recommended the continued use of the medication given that day . Finally , a clinical team made recommendations for treatment taking into account each child 's individual response . Results . Both drugs were routinely superior to placebo and produced dramatic improvements in rates of negative behavior , academic productivity , and staff/parent ratings of behavior . The doses of Adderall that were assessed produced greater improvement than did the assessed doses of Ritalin , particularly the lower dose of Ritalin , on numerous but not all measures . This result suggests that the doses of Adderall used were functionally more potent than those for Ritalin . Adderall was generally superior to the low dose of Ritalin when the effects of Ritalin were wearing off at midday and late afternoon/early evening . The lower dose of Adderall produced effects comparable to those of the higher dose of Ritalin . Both drugs produced low and comparable levels of clinical ly significant side effects . Staff clinical recommendations for continued medication favored Adderall three to one . Almost 25 % of the study participants were judged to be nonresponders by the clinical team , presumably because of their large beneficial response to the concurrent behavioral intervention and minimal incremental benefit from medication . Conclusions . This is the first investigation to assess comparable doses of Adderall and Ritalin directly . Results showed that Adderall is at least as effective as Ritalin in improving acutely the behavior and academic productivity of children with ADHD . These results show clearly that Adderall should be added to the armamentarium of effective treatment for ADHD , particularly for children in whom the effects of Ritalin dissipate rapidly and a longer acting medication is desired . Measures taken at times of the day when Ritalin is expected to have worn off—4 to 5 hours after ingestion — generally showed that Adderall was more effective than Ritalin at these times . The 7.5-mg twice-a-day dose of Adderall and the 17.5-mg twice-a-day dose of Ritalin produced equivalent behavioral changes . This indicates that a 5-mg dose of Adderall ( or slightly less ) is equivalent to a 10-mg dose of Ritalin , indicating that Adderall is twice as potent ; this potency ratio is similar to the well-known 1:2 ratio between d-amphetamine and methylpheni date . A higher dose of Adderall did not produce incremental improvement beyond that of the 7.5-mg dose , and parents were less likely to desire the continuation of the higher Adderall dose than the other medication conditions . Three-quarters of the responders to medication were recommended the lower rather than higher of the doses assessed . These findings are similar to our previous reports that there is a diminishing incremental value with stimulant medications beyond low to moderate doses , particularly when a behavioral intervention is concurrently implemented . Time-course results indicated that the afternoon dose of medication seemed to have a larger effect than the morning dose , raising the possibility that afternoon doses of stimulant medication may be able to be reduced relative to the morning dose without a corresponding reduction in efficacy . Although this practice is commonly used with some cases in clinical setting s , it is almost never used in empirical investigations and no studies have systematic ally investigated the practice . Our results suggest that systematic studies of a reduced midday dose are indicated . Further studies of dose equivalence and dose-response , including mg/kg dosing rather than absolute dosing , are necessary to firmly establish the Adderall : Ritalin dosing ratio and guidelines for clinical practice . Studies comparing Adderall to d-amphetamine should be conducted to determine whether the compound is superior to d-amphetamine alone . Further examinations of time-course are necessary to determine the length of action of Adderall — for example , whether a single morning dose will be sufficient to provide coverage throughout the school day", "OBJECTIVE To compare the dose effects of long-acting extended-release dexmethylpheni date ( ER d-MPH ) and ER mixed amphetamine salts ( ER MAS ) on attention-deficit/hyperactivity disorder ( ADHD ) symptom dimensions , global and specific impairments , and common adverse events associated with stimulants . METHODS Fifty-six children and adolescents with ADHD participated in an 8-week , double-blind , crossover study comparing ER d-MPH ( 10 , 20 , 25 - 30 mg ) and ER MAS ( 10 , 20 , 25 - 30 ) with a week of r and omized placebo within each drug period . Efficacy was assessed with the ADHD Rating Scale-IV ( ADHD-RS-IV ) , whereas global and specific domains of impairment were assessed with the Clinical Global Impressions Severity and Improvement Scales and the parent-completed Weiss Functional Impairment Scale , respectively . Insomnia and decreased appetite , common stimulant-related adverse events , were measured with the parent-completed Stimulant Side Effects Rating Scale . RESULTS Both ER d-MPH and ER MAS were associated with significant reductions in ADHD symptoms . Improvement in Total ADHD and Hyperactivity/Impulsivity symptoms were strongly associated with increasing dose , whereas improvements in Inattentive symptoms were only moderately associated with dose . About 80 % demonstrated reliable change on ADHD-RS-IV at the highest dose level of ER MAS compared with 79 % when receiving ER d-MPH . Decreased appetite and insomnia were more common at higher dose levels for both stimulants . Approximately 43 % of the responders were preferential responders to only one of the stimulant formulations . CONCLUSIONS Dose level , rather than stimulant class , was strongly related to medication response", "OBJECTIVE To evaluate the efficacy and safety of dexmethylpheni date hydrochloride ( d-MPH , Focalin ) for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d , l-threo-methylpheni date ( d , l-MPH ) . METHOD This was a r and omized , double-blind study conducted at 12 U.S. centers . One hundred thirty-two subjects received d-MPH ( n=44 ) , d , l-MPH ( n=46 ) , or placebo ( n=42 ) twice daily for 4 weeks , with titration of the dose based on weekly clinic visits . The primary efficacy variable was change from baseline to last study visit on teacher-completed Swanson , Nolan , and Pelham Rating Scale ( Teacher SNAP ) . Secondary efficacy measures included the change on parent-completed SNAP ( Parent SNAP ) , Clinical Global Impressions Scale-Improvement ( CGI-I ) score , and Math Test performance . Assessment s at home in late afternoon were included to test the hypothesis that d-MPH would have a longer duration of efficacy than d , l-MPH . Safety was assessed through monitoring occurrence and severity of adverse events and discontinuations related to them . RESULTS Treatment with either d-MPH ( p=.0004 ) or d , l-MPH ( p=.0042 ) significantly improved Teacher SNAP ratings compared with placebo . The d-MPH group showed significant improvements compared with placebo on the afternoon Parent SNAP ratings ( p=.0003 ) and scores on the Math Test ( p=.0236 ) obtained late in the afternoon at 6:00 p.m. Sixty-seven percent of patients showed improvement on d-MPH and 49 % on d , l-MPH based on CGI-I scores . Both d-MPH and d , l-MPH were well tolerated , no patient in the d-MPH group and only two patients each in the d , l-MPH and placebo groups discontinued the study . CONCLUSIONS For the treatment of ADHD , an average titrated dose of 18.25 mg/day of d-MPH is as efficacious and safe as an average titrated dose of 32.14 mg/day of d , l-MPH . Both active treatments have large effect sizes . Thus , d-MPH and d , l-MPH appear to provide similar efficacy , and d-MPH may have longer duration of action after twice-daily dosing , but additional studies are needed to determine the statistical and clinical significance of this possibility", "Objectives : The aim of this r and omized clinical trial was to assess the efficacy of memantine versus methylpheni date in the treatment of children with attention deficit hyperactivity disorder . Method : Forty participants ( 34 boys and 6 girls ) aged 6 - 11 who were diagnosed with attention deficit hyperactivity disorder based on ( DSM-IV-TR ) criteria were selected for this study . The participants were r and omly assigned to two groups : group one ( n = 22 ) received memantine and the other group ( n = 18 ) received methylpheni date for six weeks . Treatment outcomes were assessed using the Attention Deficit Hyperactivity Rating Scale and Clinical Global Impression- Severity Scale administered at baseline and at weeks 3 and 6 following the treatment . Also , a two-way repeated measures analysis of variance ( time- treatment interaction ) was used . Results : At 6 weeks , methylpheni date produced a signiﬁcantly better outcome on the Parent Rating Scale scores and Clinical Global Impression- Severity than memantine . Side effects were observed more often in the memantine group . However , with respect to the frequency of side effects , the difference between the memantine and methylpheni date groups was not signiﬁcant . The most common side effects associated with memantine are appetite suppression , headache , vomiting , nausea and fatigue . Conclusion : The results of this study revealed that although memantine was less effective than methylpheni date in the treatment of attention deficit hyperactivity disorder , it may be considered as an alternative treatment", "A recent r and omized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder ( ADHD ) in children . However , results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD . Therefore , due to these inconsistent findings , this study was design ed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylpheni date in a double blind r and omized clinical trial . Forty out patients with a DSM-IV-TR diagnosis of ADHD were study population of this trial . Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind , r and omized clinical trial . All study subjects were r and omly assigned to receive treatment using tablet of buspirone at a dose of 20 - 30 mg/day depending on weight ( 20 mg/day for 30 kg ) ( group 1 ) or methylpheni date at a dose of 20 - 30 mg/day depending on weight ( 20 mg/day for 30 kg ( group 2 ) for a 6 week double blind , r and omized clinical trial . The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV . Patients were assessed at baseline and at 21 and 42 days after the medication started . Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores . The changes at the endpoint compared to baseline were : -8.95±8.73 ( mean±SD ) and -15.60±7.81 ( mean±SD ) for buspirone and methypheni date , for Parent ADHD Rating Scale . The changes at the endpoint compared to baseline were : -9.80 ±7.06 ( mean±SD ) and -22.40±9.90 ( mean±SD ) for buspirone and methypheni date , respectively for Teacher ADHD Rating Scale . The difference between the buspirone and methylpheni date groups in the frequency of side effects was not significant except for decreased appetite , headache and insomnia that were observed more frequently in the methylpheni date group . The results of this study suggest that administration of buspirone was less effective than methylpheni date in the treatment of ADHD", "Twenty boys ( mean age , 9 + /- 2 years ) with attention deficit disorder with hyperactivity received three weeks each of dextroamphetamine sulfate ( 0.5 mg/kg/d ) , fenfluramine hydrochloride ( 0.6 mg/kg/d increased to 2.0 mg/kg/d ) , and placebo in a double-blind , r and om-order , crossover design . Half the boys also met criteria for conduct disorder . Dextroamphetamine produced immediate and marked improvement in disruptive , overactive behaviors . Fenfluramine had no effect on any behavioral measure at either the low or high dosage . Both drugs decreased levels of urinary norepinephrine , 3-methoxy-4-hydroxyphenylglycol ( MHPG ) , and vanillylm and elic acid . Fenfluramine , however , also produced a significant decrease in plasma MHPG levels and a larger decrease in urinary norepinephrine levels . It reduced urinary epinephrine levels as well , an effect opposite to that of dextroamphetamine . These findings suggest that different mechanisms of action are involved in the ability of the two drugs to reduce levels of MHPG and vanillylm and elic acid . Fenfluramine increased plasma prolactin levels and decreased platelet serotonin levels . Despite the structural similarity of the two drugs , some common overall effects on catecholamine metabolism , and similar effects on weight , fenfluramine had none of the motor activity or therapeutic effects of dextroamphetamine", "Objective : To ( i ) test whether atomoxetine is non-inferior to methylpheni date in treating symptoms of attention deficit hyperactivity disorder ( ADHD ) in paediatric patients ; and ( ii ) determine the tolerability of the two drugs . Method : This double-blind study was conducted in 6- to 16-year-old out patients with ADHD ( DSM-IV ) in China , Korea and Mexico ( January – October 2004 ) . Patients were r and omly assigned to once-daily atomoxetine ( 0.8–1.8 mg kg−1 day−1 ; n = 164 ) or twice-daily methylpheni date ( 0.2–0.6 mg kg−1 day−1 ; n = 166 ) for ∼8 weeks . Primary efficacy assessment was the comparison of response rates ( ≥40 % reduction from baseline to end point in total score ) on the Attention Deficit Hyperactivity Disorder Rating Scale-IV-Parent Version : Investigator-Administered and -Scored . Tolerability measures included , but were not limited to , the assessment of treatment-emergent adverse events ( TEAEs ) and weight . Results : Atomoxetine was non-inferior to methylpheni date in improving ADHD symptoms based on response rates ( atomoxetine , 77.4 % ; methylpheni date , 81.5 % ; one-sided 95 % lower confidence limit = −11.7 % , p = 0.404 ) . Treatment-emergent adverse effects experienced significantly more frequently in the atomoxetine group , compared with the methylpheni date group , included anorexia ( 37.2 % vs. 25.3 % ; p = 0.024 ) , nausea ( 20.1 % vs. 10.2 % ; p = 0.014 ) , somnolence ( 26.2 % vs. 3.6 % ; p ) , dizziness ( 15.2 % vs. 7.2 % ; p = 0.024 ) and vomiting ( 11.6 % vs. 3.6 % ; p = 0.007 ) , most of which were of mild or moderate severity . Atomoxetine-treated patients experienced a small but significantly greater mean weight loss from baseline to end point than methylpheni date -treated patients ( −1.2 kg vs. −0.4 kg ; p that atomoxetine is non-inferior to methylpheni date in the improvement of ADHD symptoms in paediatric out patients . Although both of the drugs were well tolerated , atomoxetine was associated with a higher incidence of TEAEs than methylpheni date", "OBJECTIVE To compare the side effect profiles of methylpheni date ( MPH ) and dexamphetamine ( DEX ) in children with attention deficit hyperactivity disorder ( ADHD ) , as well as to determine which symptoms are genuine adverse effects of stimulant medication , as opposed to aspects of the child 's underlying behavioral phenotype . DESIGN Double-blind , crossover study . SETTING Pediatric teaching hospital ambulatory behavior clinic . SUBJECTS A total of 125 children with ADHD with a mean age of 104.8 months . INTERVENTIONS Subjects received DEX ( 0.15 mg/kg/dose ) and MPH ( 0.3 mg/kg/dose ) twice a day for 2 weeks each in a r and omized order . OUTCOME MEASURES The Barkley Side Effects Rating Scale ( 17 symptoms ; 0 = absent , severity rated from 1 to 9 ) was completed by parents at baseline and at the completion of each trial fortnight . RESULTS Subjects ' parents reported a significantly greater mean number ( 8.19 ) and mean severity ( 4.08 ) of \" side effects \" before commencing the trial than during the MPH period ( number 7.19 ; severity 3.24 ) , but not the DEX period ( number 7.64 , severity 3.73 ) . The mean severity ( but not mean number ) was greater on DEX than on MPH . DEX caused more severe insomnia and appetite suppression compared with the baseline rating . Appetite suppression was the only item rated more severe on MPH than at baseline . Six side effects were significantly more severe on DEX than MPH : insomnia , irritability , proneness to crying , anxiousness , sadness/unhappiness , and nightmares . None were more severe on MPH than DEX . Overall , both MPH and DEX were well tolerated by most subjects , with only four subjects discontinuing the trial period because of severe adverse effects ( 2 -1.6%- on each stimulant ) . CONCLUSIONS Many symptoms commonly attributed to stimulant medication are actually preexisting characteristics of children with ADHD and improve with stimulant treatment . At the doses investigated , both DEX and MPH caused appetite suppression , and DEX caused insomnia . Negative emotional symptoms were more severe on DEX than MPH", "Attention-Deficit/Hyperactivity Disorder ( ADHD ) is the most prevalent psychiatric disorder currently afflicting children and is among the most common chronic conditions affecting school-age children . Modafinil is structurally different from the psychostimulants that are typically used to treat ADHD and has been reported to be effective in improving the symptoms of ADHD . The aim of the present study was to further evaluate , under double blind and controlled conditions , the efficacy of modafinil for ADHD in children and adolescents as compared to methylpheni date . Patients included 60 out patients , children ( 47 boys and 13 girls ) between the ages of 6 - 15 who clearly met the DSM-IV-TR diagnostic criteria for ADHD . Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind , r and omized clinical trial . All study subjects were r and omly assigned to receive either treatment with modafinil film coated tablet ( in doses of 200 - 300 mg/day ) depending on weight ( 200 mg/day for 30 kg ) ( group 1 ) or methylpheni date ( in doses of 20 - 30 mg/day ) depending on weight ( 20 mg/day for 30 kg ) ( group 2 ) . The principal measure of outcome was the Teacher and Parent ADHD Rating Scale-IV . Patients were assessed at baseline and at 21 and 42 days after the medication started . No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores . Side effects of decreased appetite and difficulty falling asleep were observed more in the methylpheni date group . The results of this study indicate that modafinil significantly improved symptoms of ADHD and was well tolerated and it is beneficial in the treatment of children with ADHD", "The objective of this study was to investigate the effects of methylpheni date ( MPH ) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder ( ADHD ) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were . In addition to MPH , two other drugs were administered in order to affect both transmitter systems more selectively , L-dopa ( dopamine ( DA ) agonist ) and desipramine ( DMI ) ( noradrenaline ( NA ) re-uptake inhibitor ) . Sixteen children with ADHD performed a stop-task , a laboratory task that measures the ability to inhibit an ongoing action , in a double-blind r and omized within-subjects design . Each child received an acute clinical dose of MPH , DMI , L-dopa , and placebo ; measures of performance and plasma were determined . The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa . The response-time to the stop-signal was marginally shortened after intake of DMI . MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone . No effects of L-dopa whatsoever were noted . Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo . It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms . The improved inhibition under DMI could be serotonergically mediated", "STUDY OBJECTIVES This study compared the effects of atomoxetine and methylpheni date on the sleep of children with attention-deficit/hyperactivity disorder ( ADHD ) . This study also compared the efficacy of these medications for treating ADHD in these children . DESIGN R and omized , double-blind , crossover trial . SETTING Two sleep disorders centers in the United States ; 1 in a private- practice setting and 1 in a hospital setting . PATIENTS 85 children diagnosed with ADHD . INTERVENTIONS Twice-daily atomoxetine and thrice-daily methylpheni date , each for approximately 7 weeks . MEASUREMENTS AND RESULTS Relative to baseline , the actigraphy data indicated that methylpheni date increased sleep-onset latency significantly more than did atomoxetine ( 39.2 vs 12.1 minutes , p slept better with atomoxetine , compared with methylpheni date . Parents reported that it was less difficult getting their children up and getting them ready in the morning and that the children were less irritable , had less difficulty getting ready for bed , and had less difficulty falling asleep with atomoxetine , compared with methylpheni date . There were no significant differences between medications using the main measures of efficacy for ADHD treatment . Atomoxetine was superior on some secondary ADHD treatment-efficacy measures , based on parent reports . The only significant differences in treatment-emergent adverse events were greater incidence of decreased appetite and greater incidence of insomnia with methylpheni date . CONCLUSIONS Patients receiving twice-daily atomoxetine had shorter sleep-onset latencies , relative to thrice-daily methylpheni date , based on objective actigraphy and polysomnography data . Although both medications decreased nighttime awakenings , the decrease was greater for methylpheni date", "Attention-deficit hyperactivity disorder ( ADHD ) is a common disorder of childhood that affects 3 - 6 % of school children . Conventional stimulant medications are recognized as useful symptomatic treatments by both specialists and parents . Nevertheless , approximately 30 % of ADHD children treated with them do not respond adequately or can not tolerate the associated adverse effects . Such difficulties highlight the need for alternative , safe and effective medications in the treatment of this disorder . Theophylline is a psychomotor stimulant most widely used as a broncodilator . Purinergic modulation may be therapeutically beneficial in the treatment of psychiatric disorders . We hypothesized that theophylline would be beneficial for the treatment of ADHD and report results of a trial of theophylline compared with methylpheni date for the treatment of ADHD . A total of 32 children with ADHD as defined by DSM IV were r and omized to theophylline and methylpheni date dosed on an age and weight-adjusted basis at 4 mg/kg/day ( under 12 years ) and 3 mg/kg/day theophylline ( over 12 years ) ( group 1 ) and 1 mg/kg/day methylpheni date ( group 2 ) for a 6-week double-blind and r and omized clinical trial . The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale . Patients were assessed by a child psychiatrist , at baseline and at 14 , 28 and 42 days after start of the medication . No significant differences were observed between theophylline and methylpheni date on the Parent and Teacher Rating Scale scores over the trial ( t = 0.49 , d.f . = 24 P = 0.62 and t = 0.19 , d.f . = 24 P = 0.54 respectively ) . Although the number of dropouts in the methylpheni date group was higher than the theophylline group , there was no significant difference between the two protocol s in terms of the dropouts . In addition , headaches were observed more often in the methylpheni date group . The results suggest that theophylline may be a useful for the treatment of ADHD . In addition , a tolerable side-effect profile is one of the advantages of theophylline in the treatment of ADHD . Nevertheless , our study is small and our results would need to be confirmed in a larger study", "Attention deficit hyperactivity disorder ( ADHD ) is a common disorder of childhood that affects 3 % to 6 % of school-age children . Conventional stimulant medications are recognized by both specialists and parents as useful symptomatic treatment . Nevertheless , approximately 30 % of ADHD children treated with them do not respond adequately or can not tolerate the associated adverse effects . Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder . Selegiline is a type B monoamine oxidase inhibitor ( MAOI ) that is metabolized to amphetamine and methamphetamine stimulant compounds that may be useful in the treatment of ADHD . The authors undertook this study to further evaluate , under double-blind and controlled conditions , the efficacy of selegiline for ADHD in children . A total of 28 children with ADHD as defined by DSM IV were r and omized to selegiline or methylpheni date dosed on an age and weight-adjusted basis at selegiline 5 mg/day ( under 5 years ) and 10 mg/day ( over 5 years ) ( Group 1 ) and methylpheni date 1 mg/kg/day ( Group 2 ) for a 4-week double-blind clinical trial . The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale . Patients were assessed by a child psychiatrist at baseline , 14 and 28 days after the medication started . No significant differences were observed between the two protocol s on the Parent and Teacher Rating Scale scores . Although the number of dropouts in the methylpheni date group was higher than in the selegiline group , there was no significant difference between the two protocol s in terms of the dropouts . Decreased appetite , difficulty falling asleep and headaches were observed more in the methylpheni date group . The results of this study must be considered preliminary , but they do suggest that selegiline may be beneficial in the treatment of ADHD . In addition , a tolerable side effect profile may be considered as one of the advantages of selegiline in the treatment of ADHD", "OBJECTIVE To compare the efficacy and time course of single morning doses of Adderall , extended-release , and immediate-release dextroamphetamine sulfate . METHOD Thirty-five children with attention-deficit/hyperactivity disorder , combined type , were given Adderall , immediate-release dextroamphetamine , dextroamphetamine Spansules , and placebo in a r and omized , double-blind , crossover study . Behavior ratings , locomotor activity measurements , and academic measures were obtained over a period of 8 weeks . RESULTS All three drugs exhibited robust efficacy versus placebo on nearly all measures . The effects of dextroamphetamine Spansules were less robust in the morning , particularly compared with Adderall , but they lasted 3 to 6 hours longer , depending on the measure . Although parent behavior ratings and locomotor activity showed improvements up to 12 hours after single doses of all three drugs , the number of math problems attempted and completed correctly 4 hours after dosing were only robustly increased by Spansules . CONCLUSIONS Both immediate-release amphetamines demonstrated earlier onset of effects , but dextroamphetamine Spansules showed more sustained effects that were present on a wider range of measures", "Objective We sought to determine the dose-response effects of extended-release ( ER ) dexmethylpheni date ( d-MPH ) and ER mixed amphetamine salts ( MAS ) on objective measures of sleep . Methods This was an 8-week , double-blind , placebo-controlled , r and omized , two period , crossover study of youth with attention-deficit hyperactivity disorder ( ADHD ) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children – Present and Lifetime version ( K-SADS-PL ) . Children aged 10–17 years were recruited from clinical practice , colleague referrals , and flyers . Participants were r and omized to initially receive either d-MPH or MAS . During each 4-week drug period , children received three dose levels ( 10 , 20 , and 25/30 mg ) in ascending order , with placebo substituted for active medication in a r and omized fashion during 1 week of the study . After 4 weeks , participants were switched to the alternative medication for another 4 weeks of treatment . The main outcome measure was sleep duration as measured by actigraphy . Children , parents , and research ers were blinded to drug , dose , and placebo status . Results Sixty-five participants met the inclusion criteria and were enrolled in the study . Of these , 37 participants with sufficient sleep data for analysis were included . Sleep schedule measures showed a significant effect for dose on sleep start time ( F(1,36 ) = 6.284 ; p sleep start time when children were receiving 20- or 30-mg doses , compared with placebo ( p on actual sleep duration ( F(1,36 ) = 8.112 ; p actual sleep duration for subjects receiving 30 mg compared with those receiving placebo ( p sleep duration or sleep schedule between the two stimulant medications . The trial is complete and closed to follow-up . Conclusions Higher stimulant doses were associated with reduced sleep duration and later sleep start times , regardless of medication class . Trial registration Clinical Trials.gov : NCT00393042", "OBJECTIVE Because models of attention-deficit/hyperactivity disorder ( ADHD ) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling , strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses . This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist , d-methylpheni date extended-release ( DMPH ) with guanfacine ( GUAN ) , an α2A receptor agonist , would be clinical ly superior to either monotherapy and would have equal tolerability . METHOD An 8-week , double-blind , 3-arm , comparative trial r and omized 7- to 14-year-olds with DSM-IV ADHD to GUAN ( 1 - 3 mg/day ) , DMPH ( 5 - 20 mg/day ) , or a combination ( COMB ) with fixed-flexible dosing . Outcome measures were the ADHD Rating Scale IV ( ADHD-RS-IV ) and the Clinical Global Impression-Improvement ( CGI-I ) scale . Data on adverse events and safety measures were obtained . RESULTS A total of 207 participants were r and omized and received drug . Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total ( p = .0001 ) and inattentive symptoms ( p = .0001 ) . COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies ( DMPH : p = .05 ; f(2 ) = .02 ; and GUAN : p = .02 ; f(2 ) = .02 ) , and was associated with a greater positive response rate by CGI-I ( p = .01 ) . No serious cardiovascular events occurred . Sedation , somnolence , lethargy , and fatigue were greater in both guanfacine groups . All treatments were well tolerated . CONCLUSION COMB showed consistent evidence of clinical benefits over monotherapies , possibly reflecting advantages of greater combined dopaminergic and α2A agonism . Adverse events were generally mild to moderate , and COMB treatment showed no differences in safety or tolerability . CLINICAL TRIAL REGISTRATION INFORMATION Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder ( Project1 ) ; http:// clinical trials.gov/ ; NCT00429273", " Fourteen boys ( mean age , 9.2 + /- 1.5 years ) with Attention Deficit Disorder ( ADD ) With Hyperactivity were treated with dextroamphetamine sulfate or a monoamine oxidase inhibitor ( MAOI ) ( six received clorgyline , eight received tranylcypromine sulfate ) for four weeks each in a double-blind , cross-over study that included a two-week placebo washout between active drug periods . The MAOIs had immediate , clinical ly significant benefit and were clinical ly indistinguishable from dextroamphetamine . Most children responded to both stimulant and MAOI . These findings of equivalent efficacy of MAOIs in ADD are in contrast to our previous studies with neurotransmitter system selective agents , which showed only weak effects , and suggest that multiple neurotransmitter alterations may be required for stimulant drug effects in ADD . The immediate response to MAOIs indicates a different mechanism from that mediating antidepressant effect . The MAOIs may be useful alternate treatments in selected cases of ADD", "OBJECTIVE In the treatment of attention-deficit hyperactivity disorder ( ADHD ) , the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitor antidepressants has been compared with that of both placebo and the stimulants ( methylpheni date and /or dextroamphetamine ) . However , the effectiveness of bupropion has been contrasted only with placebo . The primary aim of this study was to contrast the efficacy of bupropion with that of methylpheni date in the treatment of ADHD . METHOD A double-blind , crossover design was used in this study . After a 14-day medication washout period , 15 ADHD subjects ( 7 to 17 years old ) were r and omized to either methylpheni date or bupropion for 6 weeks , washed out for an additional 2 weeks , and then \" crossed over \" to the other drug . Methylpheni date was titrated to the maximum effective dose of 0.4 to 1.3 mg/kg per day ( mean 0.7 mg/kg per day ) and bupropion was titrated to an effective dose ranging from 1.4 to 5.7 mg/kg per day ( mean 3.3 mg/kg per day ) . RESULTS Both methylpheni date and bupropion produced significantly greater ( p Iowa-Conners Teacher 's Rating Scale according to both the subjects ' parents and teachers . The same pattern of improvement was also noted for improvement on the Clinical Global Impression Scale , Kagan 's Matching Familiar Figures Test , Continuous Performance Test , Children 's Depression Inventory , Children 's Manifest Anxiety Scale , and Rey Auditory-Verbal Learning Test . CONCLUSIONS In this double-blind , crossover trial , bupropion and methylpheni date were both effective and did not differ in their overall efficacy as treatments for ADHD", "Double-blind crossover comparison of methylpheni date hydrochloride , dextroamphetamine sulfate , and caffeine after placebo washout in 29 children with minimal brain dysfunction ( MBD ) showed on six ratings that methylpheni date and dextroamphetamine were significantly ( P less than .05 to P less than .001 ) better than placebo and caffeine , but not significantly ( P less than .05 ) different from each other . Placebo , caffeine , and ratings before drug did not differ significantly . Of 26 drug responders , 12 responded best to dextroamphetamine , ten to methylpheni date , and one to caffeine . The latter child showed no improvement at all with either prescription stimulant . Methylpheni date and dextroamphetamine were each efficacious for six children who did not respond to the other stimulant . All three drugs showed significant ( P less than .05 ) weight loss and cardiovascular side effects , the latter possibly spurious . Dextroamphetamine showed a significant ( P less than .05 ) decrease from placebo in \" tummyaches .", "Mixed amphetamine salts extended release ( MAS XR ; Adderall XR ® ) and atomoxetine ( Strattera ® ) were compared in children 6 to 12 years old with attention deficit/hyperactivity disorder ( ADHD ) combined or hyperactive/impulsive type in a r and omized , double-blind , multicenter , parallel-group , forced-dose-escalation laboratory school study . Primary efficacy measure was the SKAMP ( Swanson , Kotkin , Agler , M-Flynn , and Pelham ) behavioral rating scale . Changes in mean SKAMP deportment scores from baseline were significantly greater for MAS XR ( n = 102 ) than for atomoxetine ( n = 101 ) overall ( -0.56 and -0.13 , respectively ; p ( p events were similar for both treatment groups . The extended time course of action and greater therapeutic efficacy of MAS XR suggests that it is more effective than atomoxetine in children with ADHD", "In this double-blind , crossover study of 8 boys with minimal brain dysfunction , 20 mg of methylpheni date daily was significantly better than 160 mg of caffeine in controlling behavior , especially impulsivity and hyperactivity , and methylpheni date alone was superior to decaffeinated coffee and placebo . The tentative results of this study confirm the primary position of sympathomimetics in the pharmacotherapy of minimal brain dysfunction and , in addition , suggest the involvement of dopamine pathways in this disorder . The authors urge further study of this hypothesis", "OBJECTIVE To examine the safety and tolerability of clonidine used alone or with methylpheni date in children with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD In a 16-week multicenter , double-blind trial , 122 children with ADHD were r and omly assigned to clonidine ( n = 31 ) , methylpheni date ( n = 29 ) , clonidine and methylpheni date ( n = 32 ) , or placebo ( n = 30 ) . Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylpheni date ( both with divided dosing ) . Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs . RESULTS There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine ( 17.5 % versus 3.4 % ; p = .02 ) , but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes . There were no suggestions of interactions between clonidine and methylpheni date regarding cardiovascular outcomes . Moderate or severe adverse events were more common in subjects on clonidine ( 79.4 % versus 49.2 % ; p = .0006 ) but not associated with higher rates of early study withdrawal . Drowsiness was common on clonidine , but generally resolved by 6 to 8 weeks . CONCLUSIONS Clonidine , used alone or with methylpheni date , appears safe and well tolerated in childhood ADHD . Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness", "Chlorpromazine , dextroamphetamine and methylpheni date were significantly superior to placebo in producing overall improvement in the behaviour of hyperactive children . Chlorpromazine was effective for the majority of the children , but reduced only hyperactivity , having no demonstrable effect on distractibility , aggressivity or excitability . Both stimulants produced more goal -oriented behaviour and reduced distractibility . Methylpheni date was the most effective of the drugs in prpducing exceptional improvement . All three active drugs had to be discontinued in a few of the children because of side effects . Not all hyperactive children were benefited by the drugs . No background variables ( with the exception of mother-child relationship ) were found in the present studies to predict favourable response to the drugs . Methylpheni date became our drug of choice for this group of hyperactive children", "OBJECTIVE The aim of the present study was to further evaluate , under double blind and controlled conditions , the efficacy of amantadine for attention-deficit/hyperactivity disorder ( ADHD ) in children and adolescents as compared to methylpheni date . METHODS This was a 6-week r and omized clinical trial . Forty patients ( 28 boys and 12 girls ) with a DSM-IV-TR diagnosis of ADHD were the study population of this trial . All study subjects were r and omly assigned to receive the treatment using capsule of amantadine at a dose of 100 - 150 mg/day depending on weight ( 100 mg/day for 30 kg ) or methylpheni date at a dose of 20 - 30 mg/day for a 6-week double blind , r and omized clinical trial . The principal measure of outcome was the Teacher and Parent Attention deficit/hyperactivity disorder Rating Scale-IV . RESULTS No significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores ( df = 1 ; F = 0.02 ; p = 0.86 and df = 1 ; F = 0.01 ; p = 0.89 , respectively ) . Side effects of decreased appetite and restlessness were observed more frequently in the methylpheni date group . CONCLUSION The results of this study indicate that amantadine significantly improved symptoms of ADHD and was well tolerated and it may be beneficial in the treatment of children with ADHD . Nevertheless , the present results do not constitute proof of efficacy", "BACKGROUND Lisdexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine , a naturally occurring amino acid . Pharmacologically active d-amphetamine is released from lisdexamfetamine following oral ingestion . METHODS This phase 2 , r and omized , double-blind , placebo- and active-controlled crossover study compared the efficacy and safety of lisdexamfetamine ( LDX : 30 , 50 , or 70 mg ) with placebo , with mixed amphetamine salts extended-release ( MAS XR : 10 , 20 , or 30 mg ) included as a reference arm of the study , in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder ( ADHD ) in an analog classroom setting . The primary efficacy measure was the Swanson , Kotkin , Agler , M-Flynn , and Pelham ( SKAMP ) Rating Scale ; secondary efficacy measures included the Permanent Product Measure of Performance ( PERMP ) Derived Measures , and the Clinical Global Impression ( CGI ) Scale . RESULTS LDX treatment significantly improved scores on SKAMP-deportment , SKAMP-attention , PERMP-attempted , PERMP-correct , and CGI-improvement from baseline . Adverse events were similar for both active treatments . CONCLUSIONS In a laboratory classroom environment , LDX significantly improved ADHD symptoms versus placebo in school-age children with ADHD", "The authors compared the efficacy of caffeine , methylpheni date , and d-amphetamine in children with minimal brain dysfunction using a double-blind crossover design . The slight improvement with caffeine was not significantly better than placebo . Both prescription drugs result ed in significant improvement and were significantly superior to caffeine . The authors suggest that the discrepancy between these results and an earlier , more optimistic report mat stem from the use in this study of pure caffeine rather than whole coffee", "The present study compared the behavioral performance of 30 children with attention deficit disorder with hyperkinesis ( HK ) on electrophysiological , biochemical , behavioral , and psychometric measurements . HK children were partitioned into cells of 10 and were then treated with placebo , methylpheni date , and adrenocorticotropic hormone fractions ( ACTH4–9 analog ) , respectively , in a double-blind r and omized cell sequence according to body weight . The results revealed that HK children on methylpheni date manifested a significantly greater vasomotor reactivity , behavioral improvement , and learning receptivity than did HK children taking ACTH4–9 analog and /or placebo . Future research implication s with ACTH4–9 and HK children are discussed", "OBJECTIVE To determine the efficacy and safety of clonidine , used alone or in combination with methylpheni date , in treating attention-deficit/hyperactivity disorder ( ADHD ) . METHOD A 16-week , r and omized , double-blind , placebo-controlled clinical trial was conducted in 122 children , ages 7 to 12 , with any subtype of ADHD , r and omly assigned to clonidine , methylpheni date , clonidine in combination with methylpheni date , or placebo according to a 2 x 2 factorial design . In two successive 4-week titration periods , clonidine ( or matching placebo ) and added methylpheni date ( or matching placebo ) were adjusted to optimal doses and then continued for 8 weeks . The primary efficacy outcome was changed from baseline to week 16 on the Conners Teachers Abbreviated Symptom Question naire . Secondary outcomes included the Conners Abbreviated Symptom Question naire for Parents and the Children 's Global Assessment Scale . RESULTS On the Conners Teachers Abbreviated Symptom Question naire , clonidine was not found to improve ADHD symptoms , whereas subjects treated with methylpheni date showed significant improvement compared to those not treated with methylpheni date . Subjects treated with clonidine had greater improvements on the Conners Abbreviated Symptom Question naire for Parents and Children 's Global Assessment Scale , but also a higher rate of sedation compared with subjects not treated with clonidine . CONCLUSIONS Based on the Conners Teachers Abbreviated Symptom Question naire , methylpheni date offers the best combination of efficacy and tolerability for ADHD . Clonidine was well tolerated despite the frequency of sedation and did offer some benefit", "OBJECTIVE The purpose of this study was to assess the efficacy and safety of edivoxetine ( LY2216684 ) , a selective norepinephrine reuptake inhibitor , in pediatric patients with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD A fixed-dose , r and omized , double-blind , 8 week study was conducted in patients 6 - 17 years of age , who were r and omized by two strata : 1 ) Patients with prior stimulant use r and omized to placebo , edivoxetine 0.1 mg/kg/day , 0.2 mg/kg/day , or 0.3 mg/kg/day arms in a 1:1:1:1 ratio ; 2 ) Stimulant-naïve patients r and omized to placebo , edivoxetine 0.1mg/kg/day , 0.2 mg/kg/day , 0.3 mg/kg/day , or osmotic-release oral system methylpheni date ( OROS MPH ) ( 18 - 54 mg/day based on body weight ) arms in a 1:1:1:1:1 ratio . The primary efficacy measure was baseline-to-week 8 change of ADHD Rating Scale ( ADHD-RS ) total score for edivoxetine 0.2 mg/kg/day and 0.3 mg/kg/day . RESULTS A total of 340 patients were r and omized to placebo ( n=78 ) ; edivoxetine 0.1 mg/kg/day ( n=76 ) , 0.2 mg/kg/day ( n=75 ) , or 0.3 mg/kg/day ( n=75 ) ; or OROS MPH ( n=36 ) . In the stimulant-naïve stratum , the positive control , OROS MPH , was significantly superior to placebo in mean ADHD-RS total score change at end-point ( -19.46 , p=0.015 ) . The edivoxetine 0.2 mg/kg/day and 0.3 mg/kg/day arms had statistically significantly greater improvement than the placebo arm in mean ADHD-RS total score change at end-point ( placebo -10.35 ; edivoxetine 0.2 mg/kg/day -16.09 , p edivoxetine 0.3 mg/kg/day -16.39 , p Clinical Global Impressions-Improvement score ( placebo 3.05 ; edivoxetine 0.1 mg/kg/day 3.01 , p=0.860 ; edivoxetine 0.2 mg/kg/day 2.54 , p=0.013 ; edivoxetine 0.3 mg/kg/day 2.53 , p=0.013 ) . In the overall efficacy-analyses data set ( n=270 ) , the effect size estimates for edivoxetine doses 0.1 mg/kg/day , 0.2 mg/kg/day and 0.3 mg/kg/day at the week 8 time point were 0.17 , 0.51 , and 0.54 , respectively ( for the stimulant-naïve stratum , the effect size estimate for OROS MPH was 0.69 ) . Compared with placebo , edivoxetine treatment was associated with statistically significant increases in blood pressure and pulse ( p decrease in weight . CONCLUSIONS Edivoxetine at doses of 0.2 mg/kg/day and 0.3 mg/kg/day demonstrated efficacy in ADHD treatment , despite the presence of a sizeable placebo response . No unexpected adverse events were identified . Clinical Trial Registry identifier : NCT00922636", "In a nine-week double-blind crossover comparison of dextroamphetamine , levoamphetamine ( Cydril ) , and placebo with 11 hyperkinetic children , effects were assessed by an established teacher rating scale , a parent rating scale , and a new tool , weekly quantification of parent-selected target symptoms . Both active drugs were significantly more effective than placebo . Dextroamphetamine seemed consistently superior to levoamphetamine , though not to a significant degree ( on this size sample ) . Levoamphetamine seemed \" slower starting , \" requiring three weeks to show significant benefit on target symptoms , whereas dextroamphetamine showed nearly its maximum benefit the first week . Levoamphetamine seemed better for hyperactivity and aggressiveness than for inattentiveness , whereas dextroamphetamine seemed equally beneficial for all three . These data are consistent with the possibility that therapeutic effects of amphetamine on hyperkinetic children are mediated , at least in some , by dopaminergic systems", "OBJECTIVES The aim of this study was to examine the selegiline treatment compared to methylpheni date ( MPH ) in children and adolescents with attention deficit hyperactivity disorder ( ADHD ) . METHOD Forty subjects , aged 6 - 15 years , boys and girls , who were diagnosed as having ADHD , using the criteria of the Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition ( DSM-IV ) , were r and omly assigned to receive either selegiline or MPH for 60 days . Treatment outcomes were assessed using the Attention Deficit Hyperactivity Scale ( ADHS ) administered at baseline and on days 14 , 28 , 42 , and 60 following the commencement of treatment . Side effects were also rated . RESULTS There were no significant differences between sex , age , weight , and ethnicity of participants in the 2 groups . Both groups showed a significant improvement over the 60 days of treatment result ing from the teachers ' and parents ' ADHS scores across the treatment . CONCLUSION Following the trial , MPH did not effect greater mean improvement as a result of the parents ' or teachers ' ADHS scores than selegiline . Thus , selegiline appears to be effective and well tolerated for ADHD in children and adolescents", "The purpose of this study was to examine the efficacy and side-effects of pindolol , a beta-blocker , in children with attention-deficit hyperactivity disorder ( ADHD ) . Fifty-two ADHD children , 7 - 13 years old , participated in a prospect i ve double-blind placebo-controlled comparison of pindolol and methylpheni date ( MPH ) . Active treatment was pindolol and MPH : pindolol 20 mg b.i.d . or MPH 10 mg b.i.d . for 4 weeks . The outcome was assessed on the basis of the Abbreviated Conners Rating Scales ( ACRS ) completed by parents , teachers , and by a psychologist during psychological testing . Pindolol treatment was associated with a higher incidence of paraesthesias and with more intense nightmares and hallucinations than MPH or placebo treatment . These side-effects led to an interim change in design by ending pindolol treatment after 32 participants . Pindolol proved to be just as effective as MPH in decreasing hyperactivity and conduct problems at home , and hyperactivity problems at school . Pindolol , however , had less therapeutic effects than MPH during psychological testing , and failed to affect conduct problems in school . In sum , pindolol was modestly effective in the treatment of ADHD . Safety concerns on troubling side-effects clearly limit the use of it", "OBJECTIVE 1 ) To compare st and ard twice-daily methylpheni date ( MPH ) dosing with a single morning dose of MPH and of Adderall during a typical school-day time period , and 2 ) to conduct a dose-response study of the effects of a late-afternoon ( 3:30 PM ) dose of MPH and Adderall on evening behavior and side effects . DESIGN Within-subject , placebo-controlled , crossover design . SETTING Intensive summer treatment program with a comprehensive behavioral approach . STUDY PARTICIPANTS Twenty-one children with attention-deficit/hyperactivity disorder ( 19 boys and 2 girls ) , between the ages of 6 and 12 years . INTERVENTIONS Children received , in r and om order with daily crossovers , each of the following conditions : 1 ) placebo , 2 ) 0.3 mg/kg of MPH received 3 times , 3 ) 0.3 mg/kg of MPH received twice ( 7:30 AM and 11:30 AM ) with 0.15 mg/kg received at 3:30 PM , 4 ) 0.3 mg/kg of MPH received once in the morning only , 5 ) 0.3 mg/kg of Adderall received at 7:30 AM and at 3:30 PM , 6 ) 0.3 mg/kg of Adderall once in the morning with 0.15 mg/kg received at 3:30 PM , 7 ) 0.3 mg/kg of Adderall received in the morning only . OUTCOME MEASURES Daily rates of behaviors in social and academic setting s , and st and ardized ratings from counselors and teachers , were assessed for the hours between 8:00 AM and 3:30 PM ( a typical school-day ) . Relative sizes of the medication effects were compared hourly between first daily ingestion ( 7:30 AM ) and 4:45 PM to assess the time course of the 2 drugs . Effects of the 3:30 PM doses on functioning in the evenings at home were evaluated using parent ratings of behavioral and side effects . RESULTS A single morning dose of Adderall produced equivalent behavioral effects to those of MPH received twice-daily and behavioral effects of that single morning dose lasted throughout the school-day period . One morning dose of MPH was less effective than either 2 daily doses of MPH or 1 dose of Adderall , and seemed to wear off in the early to mid-afternoon . For some children a single morning dose of MPH maintained their behavior for an entire school day in the context of the summer treatment program . On parent ratings of evening behavior , 0.3 mg/kg of MPH at 3:30 PM was superior to 0.15 mg/kg at 3:30 PM , but there was no difference between the 2 doses of Adderall . Compared with placebo at 3:30 PM , only the 0.3 mg/kg dose of MPH caused significant improvement in parent ratings . In placebo versus Adderall comparisons , all doses , even the condition that consisted of Adderall in the morning and placebo at 3:30 PM , produced a significant change in evening behavior . CONCLUSIONS The results show that , at least in the context of an intensive behavioral intervention , a single morning dose of Adderall had behavioral effects throughout an entire school day period that were equivalent to st and ard twice-daily MPH dosing . These results indicate that Adderall may be used as a long-acting stimulant for children for whom midday dosing is a problem . Further study including dose-response comparisons , effects in regular school setting s , and direct comparisons with comparable doses of MPH and d-amphetamine will help to clarify the time course and relative advantages of Adderall", "OBJECTIVE To compare the safety and efficacy of bupropion with methylpheni date in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS In a 6-week r and omized double-blind study , 44 patients with a DSM-IV-TR diagnosis of ADHD were r and omly assigned to receive bupropion 100 - 150 mg/day ( 100 mg/day for 30 kg and 150 mg/day for > 30 kg ) or methylpheni date 20 - 30 mg/day . Symptoms were assessed using Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV ( ADHD-RS-IV ) at baseline and weeks 3 and 6 . RESULTS Forty patients had at least one post-baseline measurement , and 38 patients completed the trial . No significant difference was found between the two groups on the Parent and Teacher ADHD-RS-IV scores ( [ F(1 , 38 ) = 0.266 , p = 0.609 ] and [ F(1 , 38 ) = 0.001 , p = 0.972 ] , respectively ) . By week 6 , 18 patients ( 90 % ) in each group achieved response on the Parent scale ( Fisher 's exact test p-value = 1.0 ) . With the Teacher ADHD-RS-IV used , eight ( 40 % ) patients in the bupropion group and 12 ( 60 % ) patients in the methylpheni date group achieved response by week 6 ( χ(2 ) ( 1 ) = 1.600 , p = 0.206 ) . Headache was observed more frequently in the methylpheni date group . Frequency of other side effects was not significantly different between the two groups . CONCLUSIONS Bupropion has a comparable safety and efficacy profile with methylpheni date in children and adolescents with ADHD", "BACKGROUND Attention deficit hyperactivity disorder ( ADHD ) is one of the most common childhood psychiatric disorder with a prevalence of 8 - 12 % . Even though psychostimulants remain the treatment of choice , its cost and availability in developing countries limits the usage of the drug . In view of free availability and low cost , a R and omized controlled study was carried out using two second line drugs ( clonidine and carbamazepine ) in a tertiary care hospital , Pondicherry , South India . OBJECTIVE To compare the efficacy of clonidine and carbamazepine in children with ADHD . METHOD With approval of ethics committee , a prospect i ve , Double-blind , R and omized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD ( age group 4 - 12 years ) , over a period of 2 years ( 2005 - 07 ) in a tertiary care hospital , Pondicherry , South India . RESULTS Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine . Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions . CONCLUSION Clonidine can be a safer and cheaper alternative in treatment of children with ADHD , with a predominant effect on their hyperactivity and impulsivity symptoms", "Double-blind crossover r and omized Latin square comparison of placebo , dextroamphetamine , and levoamphetamine in 31 consecutively diagnosed children with minimal brain dysfunction ( MBD ) replicated a smaller nonr and om study . Both isomers showed significantly more benefit than placebo but were not significantly different from each other . Dextroamphetamine showed a nonsignificant trend of superiority over levoamphetamine . Of 25 subjects who responded well to drugs , three responded only to levoamphetamine , five only to dextroamphetamine , and 17 to both . This study seems to confirm the efficacy of levoamphetamine in MBD . An unsocialized aggressive subgroup ( 308.4 ) showed a nonsignificant trend for levoamphetamine superiority , in contrast to the hyperkinetic ( 308.0 ) and overanxious ( 308.2 ) subgroups . Those who responded best to levoamphetamine tended ( not significantly ) to be from poorer functioning families . Parents ' ratings , but not teachers ' or psychiatrists ' ratings , showed significant placebo effect", "Daily academic classroom performance was recorded in a day hospital school using a commonly employed reading and math series as part of an 11-week double-blind , placebo controlled , crossover comparison of dextroamphetamine ( d-AMPH ) and methylpheni date ( MPH ) in 33 hyperactive boys . Students attempted more math and reading tasks while on either active drug . The percent correct and the number of attempted problems of the reading series improved with both drugs while the percent correct for the math series occurred with d-AMPH only . No dose-response relationship was found for either stimulant . Moderate , transient adverse effects were common for both drugs", "An eight-week double-blind comparison between pemoline ( Cylert ) , methylpheni date ( Ritalin ) hydrochloride , and placebo was carried out on 60 hyperactive children . Measurements of home , school , achievement , cognitive function , and global clinical status were made at baseline , midtreatment , end of treatment , and posttreatment . Both drugs produced improvement in all areas except the achievement measures . One major difference between drugs was the apparently longer action of pemoline , since its effects at home and school tended to persist when the drug was withdrawn , whereas the patients receiving methylpheni date tended to regress to their baseline levels", "OBJECTIVE While Adderall has been available for the treatment of attention-deficit/hyperactivity disorder ( ADHD ) for several years , there are few controlled studies comparing it to methylpheni date . METHOD Fifty-eight children with ADHD ( mean age 8.1 + /- 1.4 years ) were r and omly assigned to receive placebo , methylpheni date , or Adderall in a double-blind , parallel-group design for 3 weeks . Dosage was adjusted at the end of weeks 1 and 2 via an algorithm based on teacher and parent ratings . Final doses were 12.5 + /- 4.1 mg/day for Adderall and 25.2 + /- 13.1 mg/day for methylpheni date . Teacher and parent ratings , as well as the psychiatrist 's Clinical Global Impression ( CGI ) , were the final outcome measures at the end of week 3 . RESULTS Both medications were superior to placebo at reducing inattentive and oppositional symptoms in the classroom and on the CGI . Adderall produced significantly more improvements on teacher ratings and the CGI than methylpheni date , although the algorithm may have limited dosing in the methylpheni date group . Seventy percent of children in the Adderall group were given medication once a day , compared with 15 % of the subjects receiving methylpheni date . CONCLUSIONS Adderall compared favorably to methylpheni date , and the behavioral effects of Adderall appear to persist longer than those of methylpheni date after individual doses" ]	41186e0e-06ff-11f0-808a-c43d1ab1c353
STUDY DESIGN A systematic review . OBJECTIVE To determine predictors of outcome of multidisciplinary rehabilitation-or back school treatment for patients with chronic low back pain . SUMMARY OF BACKGROUND DATA Numerous review s have been performed to gain insight into which patients benefit from which treatment . However , no review has systematic ally focused on predictors from multiple domains ( i.e. , sociodemographic , physical , and psychological ) , or on treatment outcome measured as activity limitation or participation restriction . METHODS Studies were found by search ing medical and psychological data bases , and screening references . Two review ers independently assessed the method ological quality using st and ard criteria . Studies were only included if they met a predefined level of internal validity . A qualitative analysis was performed . RESULTS Heterogeneity among studies in patient characteristics , predictors , treatment , and outcomes limited evidence . All review ed studies were descriptive or exploratory in nature . Consistent evidence was found for the predictive value of pain intensity ( more pain-- > worse outcome ) , several work-related parameters ( e.g. , high satisfaction-- > better outcome ) , and coping style ( less active coping-- > better outcome ) . Other sociodemographic and physical variables consistently lacked predictive value . No consistent evidence was found for other psychological variables . CONCLUSIONS It is impossible to define a generic set of predictors of outcome of multidisciplinary rehabilitation and back schools for patients with chronic low back pain because the review ed studies were descriptive or exploratory in nature , and most predictors were only studied once . Nevertheless , for several predictors , consistent evidence was found . Large confirmatory studies are needed to test the value of these predictors	[ "Study Design . In this prospect i ve , observational , cohort study of 192 individuals with chronic low back pain , the group of individuals was divided based on compensation involvement , and their presentation pain and disability , treatment recommendations , and compliance were compared . For 85 of these individuals who completed a spine rehabilitation program , their pain and disability at 3 and 12 months were compared . Objectives . To test the theory that individuals with compensation involvement presented with greater pain and disability and would report less change of pain and disability after rehabilitation efforts . Background . Previous studies have produced conflicting results concerning this issue . Methods . Individuals were recruited as consecutive patients referred for consultation at a spine rehabilitation center . Pain , depression , and disability were assessed using self‐report question naires at evaluation and at 3 and 12 months . Rehabilitation services consisted of aggressive , quota‐based exercises aim ed at correcting impairments in flexibility , strength , endurance , and lifting capacity , identified through quantification of back function . Multifactoral analysis of variance models were used to control for baseline differences between compensation and noncompensation patients during analysis of target variables . Results . The compensation group included 96 patients ; these patients reported more pain , depression , and disability than the 96 patients without compensation involvement . These differences persisted when baseline differences were controlled for with multifactoral analysis of variance models . Treatment recommendations and compliance were not affected by compensation . For patients completing the spine rehabilitation program , length of treatment , flexibility , strength , lifting ability , and lower extremity work performance before and after treatment and patient satisfaction ratings were similar for the compensation and non‐compensation groups . At 3 and 12 months , improvements in depression and disability were noted for both groups , but were statistically and clinical ly less substantial for the compensation group . At the 12 month follow‐up visit , pain scores improved for the noncompensation group , but not for the compensation group . Conclusions . In chronic low back pain , compensation involvement may have an adverse effect on self‐reported pain , depression , and disability before and after rehabilitation interventions", "Study Design . A prospect i ve cohort study including patients with nonspecific spinal pain was performed . Objectives . To investigate whether the use of expert judgment in routine practice can provide a basis for reliable decision making concerning the need for intervention in patients with spinal pain and their ability to benefit from treatment . Summary of Background Data . A wide range of instruments and techniques are used to assess and treat patients with spinal pain . Many instruments are used without being clinimetrically tested . Methods . A question naire concerning the patients ’ need of treatment and their potential to assimilate it was sent to experts in the health care arena : physicians , physical therapists , social insurance officers . The experts included were those connected with patients participating in a larger outcome study . Two cohorts of patients ( sample 1 , n = 217 ; sample 2 , n = 257 ) were followed for 6 and 12 months , during which time the patients ’ health and work status were mapped . Results . No acceptable agreement was found between any of the experts ’ ratings of patients ’ needs and potential for rehabilitation . Logistic regression showed that the experts ’ judgments were based almost solely on the age of the patient . The prediction analyses showed that the most consistent predictor of the patients ’ status at the 6-month follow-up assessment was the patients ’ own belief in the existence of effective treatments and their perceived ability for learning to cope with the condition . Conclusions . Expert judgment as exercised in routine practice can not be used as basis for reliable decision making concerning the need of the patient with spinal pain for intervention and the patient ’s ability to benefit from treatment", "Study Design . A prospect i ve clinical trial was conducted that involved six groups of patients with chronic low back pain selected from a large cohort ( N = 816 ) . Objectives . To correlate pretreatment baseline variables with outcome parameters after treatment in a functional restoration program or in control programs , to identify possible factors predictive of the need for functional restoration . Summary of Background Data . Since the functional restoration program was first described , research has focused on identifying patients who will or will not benefit from such a program . The value of previous studies is limited , however , because predictive factors from a control group were not \" subtracted . \" Methods . Eight hundred sixteen patients with chronic low back disability were included . All had a structured medical examination , including various physical tests before participation in either a functional restoration program ( n = 621 ) or shorter \" control \" outpatient programs ( n = 144 ) . A smaller group of the cohort ( n = 51 ) had no treatment and served as a pure control group . Six groups were selected from the cohort : Three underwent an identical functional restoration program and three underwent different outpatient control programs . Several baseline demographic , physical , and socioeconomic variables were correlated to 1‐year outcome parameters . Results . Age , days of sick leave , connection to the work force , and back pain intensity , were significantly correlated to success 1 year after entry into the study in all groups , no matter what kind of treatment was administered . Back muscle endurance , sports activity , activity of daily living scores , and vibrations were of importance in some outcome parameters for success after functional restoration . Smoking was positively correlated to disability pension . Days of sick leave and , in functional restoration , ability to work were the only factors that were correlative with statistics for people who withdrew . Conclusions . Different factors can be identified as predictive of outcome in a functional restoration program , but most of these factors were also shown to predict success for shorter control outpatient programs or of no treatment", "The investigation of predictors for therapy outcome in patients with chronic low back pain date back to the early 1970s . Numerous well controlled prospect i ve longitudinal studies have confirmed the predominant predictive power of several psychological factors , which are in addition to objective work related , medical and sociodemographic variables . Studies published in the review period have reported markedly improved method ological st and ards . Further progress is seen with the enhanced search for predictors of working situation in chronic low back pain patients . Finally , there is a shift toward the investigation of predictors for efficacy of primary care in acute and subchronic low back pain patients", "STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and \" praying/hoping , \" \" catastrophizing , \" and \" pain behavior \" coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some \" central \" effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition", "Study Design Two-hundred-forty-three patients with chronic low back pain were studied in a prospect i ve comparative survey to determine whether the “ central ization phenomenon ” was associated with outcome after an interdisciplinary work-hardning program . Objective The hypothesis was that patients who demonstrated central ization during initial mechanical assessment would have better outcomes than non central izers . Summary of Background Data Overall subjects had decreased pain intensity ratings ( mean 10 % ) , increased lifting ability ( 6–8 kg ) , and a 59.2 % return-to-work rate at a mean of 9.7 months follow-up . Methods . Patients were classified as either central izers or non central izer , based on results of their initial assessment , changes in pain ratings , one-time maximal weights lifted , Oswestry scores , and returen-to-work status were compared between groups . Results The central izers reported significant decreases in their maximum pain ratings ( central izers , 16 % non central izers , 6 % ) and had higher return-to-work rate ( central izers , 68 % ; non central izers , 52 % ) than the non central izers . Conclusion . Centrelization can help identify subgroups within the population with chronic low back pain and could be a useful goal setting and case management toll in the rehabilitation of low back pain", "Objective The objective was to evaluate whether the Multidimensional Pain Inventory ( MPI ) is effective for predicting response to interdisciplinary treatment in a heterogeneous group of patients with chronic pain . Changes in patients ' profiles to a predominantly adaptive coping status after treatment also were assessed . Design A prospect i ve study was conducted of patients with an array of pain conditions . A st and ard evaluation battery , including measures of self-reported pain and disability , psychosocial functioning , helpfulness of the program , and medication use , was used for all patients before and after treatment . The MPI status of patients was evaluated and differential response to treatment was assessed . Methods Sixty-five consecutive patients with chronic pain were evaluated before and immediately after participation in an interdisciplinary pain treatment program . This heterogeneous pain-condition cohort was also differentiated on the basis of the MPI to evaluate potential differential response to treatment . Results Results revealed significant improvement among these patients with chronic pain when a comprehensive interdisciplinary pain-management program was administered . This improvement was seen across the variety of outcomes evaluated , including narcotic medication use . Most important , the MPI subgroup classification did not significantly predict the degree of positive treatment outcome ; all subgroups improved . Conclusions Although there were major differences in psychosocial functioning before treatment , the MPI was not found to significantly predict response to interdisciplinary treatment in a heterogeneous group of patients with chronic pain . Thus , a comprehensive interdisciplinary treatment program may achieve its full effectiveness across a wide array of pain/disability-related outcome variables , regardless of initial MPI profile categorization", "& NA ; Association of health locus of control beliefs ( HLC ) and psychological distress ( GHQ‐12 ) with short‐term outcome of low‐back pain ( LBP ) rehabilitation was studied in patients with chronic or recurrent LBP ( n = 459 ; aged 35–54 years ; 63 % men ) . These patients were r and omly assigned to 3 study groups , namely the inpatient , the outpatient and the control group . The results showed a significant decrease in disability due to LBP in the 2 treated groups ; in addition , the accomplishment and frequency of back exercises was significantly better in the treated groups . HLC beliefs were associated with a successful outcome ; those patients with stronger internal beliefs had gained more from the treatment , had learned their exercises better and had done the exercises more frequently during the follow‐up period . Symptoms of psychological distress were significantly associated with poorer accomplishment of back exercises", "Continuous prognostic factors are often categorized by defining optimized cutoff points . One component of criticism of this approach is the problem of multiple testing that leads to an overestimation of the true prognostic impact of the variable . The present study focuses on another crucial point by investigating the dependence of optimized cutoff points on the observed distribution of the continuous variable . The continuous variable investigated was the vertical tumor thickness according to Breslow , which is known to be the most important prognostic factor in primary melanoma . Based on the data of 5093 patients , stratified r and om sample s were drawn out of six artificially created distributions of tumor thickness . For each of these sample s , Cox models were calculated to explore optimized cutoff points for tumor thickness together with other prognostic variables . The optimized cutoff points for tumour thickness varied considerably with the underlying distribution . Even in sample s from the same distribution , the range of cutoff points was amazingly broad and , for some of the distributions , covered the whole region of possible values . The results of the present study demonstrate that optimized cutoff points are extremely data dependent and vary notably even if prerequisites are constant . Therefore , if the classification of a continuous prognostic factor is necessary , it should not be based on the results of one single study , but on consensus discussion s including the findings of several investigations", "& NA ; Research ers have typically used factor‐analytic composite measures of coping , instead of individual scales , to predict rehabilitation outcome . There are , however , both advantages and disadvantages to using individual or composite scores . This study extended the findings of Jensen et al. ( 1992 ) , by prospect ively comparing the individual and composite scores of the Coping Strategies Question naire ( CSQ ) in the prediction of 4 types of adjustment to low back pain . Two‐hundred patients completed the CSQ , the Oswestry Index , the SCL‐90R , and 4 lifting tasks at admission and discharge from a multidisciplinary pain clinic . Return to work was determined at 9‐month follow‐up . The CSQ scales were factor‐analyzed to devise composite indices , and the 3 result ant factors were compared to the individual scales in the prediction of pain and other outcomes . The results indicated that the relative predictive utility of the composite or individual scales depended on which outcome measure was used to define adjustment", "In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies", "& NA ; A better knowledge of differential treatment outcomes for subgroups of chronic spinal pain patients may , for instance , help clinicians in treatment planning or pain research ers in treatment outcome research . The purpose of this prospect i ve study was to evaluate the predictive validity of a subgroup classification based on the Swedish version of the ( West Haven Yale ) Multidimensional Pain Inventory , the MPI‐S. Patients referred to a vocational rehabilitation program were classified into one of three groups , labeled ‘ adaptive copers ’ , ‘ dysfunctional ’ patients , and ‘ interpersonally distressed ’ patients , and followed over an 18‐month follow‐up period . The outcome variables were absence from work ( defined as sick listing plus early retirement ) , general health status , and utilization of health care re sources . To our knowledge , the predictive validity of the MPI subgroups has not been evaluated regarding sick listing and early retirement after rehabilitation . As hypothesized , the results showed that the ‘ dysfunctional ’ patient group had significantly more registered absences from work and reported higher utilization of health care , over the follow‐up period compared to the ‘ adaptive copers ’ . Furthermore , as hypothesized , the ‘ interpersonally distressed ’ and ‘ dysfunctional ’ patient groups report a poorer general health status than the ‘ adaptive copers ’ over the whole follow‐up period . However , contrary to our hypothesis , the proportion of improved patients did not differ significantly between the subgroups . Altogether , the predictive validity of the MPI‐S subgroup classification was mainly confirmed . The clinical implication s of this study suggest that the matching of treatment to patient needs may enhance treatment outcome , reduce pain and suffering among chronic spinal pain patients and facilitate a better health economic allocation of treatment re sources", "The purpose of this study was to investigate the psychometric properties of a Dutch translation of the Multidimensional Pain Inventory , MPI-DLV . Data was available on 733 chronic pain patients . There were three issues of special interest . The first one related to the comparability between the MPI-DLV and the American and German MPI versions with regard to the psychometric aspects . The second dealt with the construct validity of the MPI-DLV scale ' general activity ' . It was predicted that patients with high scores on this scale would be in better physical condition , as measured on a working-to-tolerance bicycle ergometer test . In relation to the third issue , attention was given to the factor-invariance between fibromyalgia patients and back pain patients . From the results obtained it was concluded that ( 1 ) the factorial structure of the three MPI parts is replicated and the reliability estimates and validity indicators are similar to those from the American and German versions ; ( 2 ) patients with high scores on the ' general activity ' scale are in better physical condition and ( 3 ) MPI-DLVs of fibromyalgia and back pain patients do have similar factorial structures . Evidence was also obtained that the MPI-DLV is sensitive to treatment changes . Applications of the MPI-DLV are discussed", "Meta- analysis comprises the analysis of the data of similar studies gathered in a systematic review . If the results of the studies differ ( strongly ) , this is called heterogeneity . Possible causes of heterogeneity are : a wrong choice of type of measure of treatment effect , differences of method ological quality between studies , or real differences between studies . Heterogeneity between studies can be assessed by thorough examination of the differences between study characteristics in combination with a visual inspection of the degree of overlap of the confidence intervals of the estimates of effect of the different studies . By applying the r and om effects model for pooling , ( non- systematic ) heterogeneity between studies can be addressed . In case of heterogeneity between studies , sources of heterogeneity should be explored by means of subgroup analysis according to strict , present criteria . Subgroup analysis should address subgroups of patients within studies" ]	41186e54-06ff-11f0-808a-c43d1ab1c353
Background Fall prevention among older adults is a worldwide public health advocacy because of negative consequences of fall . Recent studies have shown that proton pump inhibitors ( PPIs ) increase the risk of fall . PPIs are among the widely prescribed medications oftentimes without clear indications . Concerns for safety of long-term use of PPIs have been raised by numerous studies . Methods A systematic review was conducted in MEDLINE and EMBASE data bases from inception through March 2018 to identify studies that assessed the association between the use of PPIs and the risk of fall . Effect estimates from the individual study were extracted and combined using r and om-effect , generic inverse variance method of DerSimonian and Laird . Results Eight observational studies with a total of 367,068 patients were enrolled . There was a significant association between the use of PPIs and the risk of fall with the pooled OR of 1.27 ( 95 % CI , 1.07 - 1.50 ) . Meta-regression showed significant positive correlations between risk of fall in patients using PPIs and year of study ( slopes = + 0.25 , p the risk of fall in patients using H2 receptor antagonists ( H2RAs ) were limited in 3 studies . The pooled OR of fall in patients using H2RAs was 0.95 ( 95 % CI , 0.75 - 1.20 ) . Conclusions We demonstrate a significant association between the use of PPIs and increased risk of fall . There is a significant positive correlation between the risk of fall in patients using PPIs and year of study . In addition , there is potentially higher risk of fall among PPIs users over time	[ "We studied the effect of proton pump inhibitors , histamine H2 receptor antagonists , and other types of antacid drugs on fracture risk . All cases were subjects with any fracture sustained during the year 2000 ( n = 124,655 ) . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of proton pump inhibitors , histamine H2 antagonists , and other antacid drugs . Adjustments were made for several confounders , including diagnosis of an ulcer , nonsteroidal anti-inflammatory drug use , use of histamine H1 antagonists , stomach resection , previous fracture , and use of corticosteroids . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose ) . Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [ odds ratio ( OR ) = 1.18 , 95 % confidence interval ( CI ) 1.12–1.43 for overall fracture risk ; OR = 1.45 , 95 % CI 1.28–1.65 for hip fractures ; and OR = 1.60 , 95 % CI 1.25–2.04 for spine fractures ) . Histamine H2 antagonists were associated with a decreased fracture risk if they had been used within the last year ( OR = 0.88 , 95 % CI 0.82–0.95 for any fracture , OR = 0.69 , 95 % CI 0.57–0.84 for hip fractures ) . Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures . Proton pump inhibitors appeared to be associated with a limited increase in fracture risk , in contrast to histamine H2 antagonists , which seemed to be associated with a small decrease in fracture risk . In all cases , the changes in risk estimates were small and the clinical significance was limited", "Background Medication use is a potentially modifiable risk factor for falling ; psychotropic and cardiovascular drugs have been indicated as main drug groups that increase fall risk . However , evidence is mainly based on studies that recorded falls retrospectively and /or did not determine medication use at the time of the fall . Therefore , we investigated the associations indicated in the literature between medication use and falls , using prospect ively recorded falls and medication use determined at the time of the fall . Methods Data from the B-PROOF ( B-vitamins for the prevention of osteoporotic fractures ) study were used , concerning community-dwelling elderly aged ≥65 years . We included 2,407 participants with pharmacy dispensing records . During the 2- to 3-year follow-up , participants recorded falls using a fall calendar . Cox proportional hazard models were applied , adjusting for potential confounders including age , sex , health status variables and concomitant medication use . Results During follow-up , 1,147 participants experienced at least one fall . Users of anti-arrhythmic medication had an increased fall risk ( hazard ratio [ HR ] 1.61 ; 95 % confidence interval [ CI ] 1.12–2.32 ) compared with non-users . Similarly , non-selective beta-blocker use was associated with an increased fall risk ( HR 1.41 [ 95 % CI 1.12–1.78 ] ) , while statin use was associated with a lower risk ( HR 0.81 [ 95 % CI 0.71–0.94 ] ) . Benzodiazepine use ( HR 1.32 [ 95 % CI 1.02–1.71 ] ) , and antidepressant use ( HR 1.40 [ 95 % CI 1.07–1.82 ] ) were associated with an increased fall risk . Use of other cardiovascular and psychotropic medication was not associated with fall risk . Conclusion Our results strengthen the evidence for an increased fall risk in community-dwelling elderly during the use of anti-arrhythmics , non-selective beta-blockers , benzodiazepines , and antidepressant medication . Clinicians should prescribe these drugs cautiously and if possible choose safer alternatives for older patients", "Background : Some recent reports suggest an increased risk of fractures with use of proton pump inhibitors ( PPIs ) and histamine type 2 receptor antagonists ( H2RAs ) , although results are inconsistent and a causal relationship has yet to be proven . As these acid-suppressive drugs may have uncommon adverse effects on the central nervous system ( CNS ) , such as dizziness , we investigated whether their use is associated with falls as a possible mechanism for increasing fracture risk . Methods : A cohort study with nested case-control analysis and two validation strategies was performed using data from UK patients ( aged 40–89 years ) included in The Health Improvement Network data base ( 2000–2008 ) . Due to the large number of falls , a r and om sample of 20,000 cases was used for the analysis . Results : The overall incidence of falls per 1000 person-years was 13.0 ( 95 % confidence interval [ CI ] = 12.9–13.1 ) . After adjustment for potential confounders , there was no relationship between falls and current use of single PPIs ( odds ratio [ OR ] = 0.95 ; 95 % CI = 0.89–1.02 ) or H2RAs ( OR = 1.01 ; 95 % CI = 0.90–1.14 ) ; there was no relationship with dose or duration of treatment . Falls were associated with CNS disorders and treatment with various pharmacological agents including antiparkinson drugs ( OR = 2.7 ; 95 % CI = 2.2–3.3 ) and antiepileptics ( OR = 2.1 ; 95 % CI = 1.8–2.3 ) . Conclusions : There was no association between falls and use of PPIs or H2RAs . Any potential increase in the risk of fractures proposed to be associated with the use of acid-suppressive drugs is not via an increased risk of falls ", "In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement", "Summary A large Canadian cohort was studied over 10 years to see if proton pump inhibitor ( PPI ) use increased the risk of sustaining a fragility fracture . We found an increased risk of fracture in individuals who used PPIs . The risk remained after controlling for other known fracture risk factors . Introduction Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture . We prospect ively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors . Methods We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study . The cohort was formed in 1995–1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use . Cox regression analyses were used to assess the association between PPI use and incident fracture risk . Results PPI use , coded as a time-dependent variable , was associated with a shorter time to first nontraumatic fracture , hazard ratio ( HR ) = 1.75 ( 95 % confidence interval ( CI ) 1.41–2.17 , p femoral neck bone density , the association remained significant , HR = 1.40 ( 95 % CI 1.11–1.77 , p = 0.004 ) . Similar results were obtained after controlling for bisphosphonate use , using PPI “ ever ” use , or when the outcome was restricted to hip fracture . Conclusions In this large prospect i ve population -based cohort study , we found an association between PPI use and increased risk of fragility fracture . Although the increased risk found was modest , this finding is important , given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures", "OBJECTIVES To determine the prevalence and economic effect of inappropriate proton pump inhibitor ( PPI ) use in an ambulatory care setting . STUDY DESIGN Retrospective medical record review of r and om sample with subgroup analysis . METHODS Patients were categorized according to appropriateness of pharmacotherapy based on documented upper gastrointestinal tract diagnoses , gastrointestinal or extraesophageal symptoms , or gastroprotection . Adverse events potentially associated with PPI use were identified . RESULTS Of 946 patients in an ambulatory care setting , 35.4 % were given PPI therapy for an appropriately documented upper gastrointestinal tract diagnosis , 10.1 % received PPIs empirically for symptomatic treatment based on extraesophageal symptoms , 18.4 % received PPIs for gastroprotection , and 36.1 % had no documented appropriate indication for PPI therapy . In a subgroup analysis , 48.6 % of patients across all 4 categories received PPIs without documentation of reevaluation of upper gastrointestinal tract symptoms , accounting for 1034 patient-years of PPI use . The total cost of inappropriate PPI use was $ 233,994 based on over-the-counter PPI costs and $ 1,566,252 based on average wholesale price costs . Potentially related adverse events in this cohort included Clostridium difficile – associated diarrhea ( 6 cases ) and community-acquired pneumonia ( 1 case ) , but no cases of hip fracture or vitamin B12 deficiency were identified . CONCLUSIONS Proton pump inhibitors are often overused in the ambulatory care setting without documented valid indications . Inappropriate use of PPIs is associated with substantial cost expenditure and with the potential for adverse events", "Proton pump inhibitors ( PPIs ) are widely used in the elderly . Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly , however the mechanism remains unknown . We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure , falls , and balance-related function in a post hoc analysis of a longitudinal population -based prospect i ve cohort of elderly postmenopausal women and replicated the findings in a second prospect i ve study of falling in elderly postmenopausal women . Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations ; adjusted odds ratio ( AOR ) 2.17 ; 95 % CI , 1.25 - 3.77 ; p = 0.006 and 1.95 ; 95 % CI , 1.20 - 3.16 ; p = 0.007 , respectively . In the replication study , long-term PPI use was associated with an increased risk of self-reported falling ; AOR , 1.51 ; 95 % CI , 1.00 - 2.27 ; p = 0.049 . No association of long-term PPI therapy with bone structure was observed ; however , question naire-assessed falls-associated metrics such as limiting outdoor activity ( p = 0.002 ) and indoor activity ( p = 0.001 ) due to fear of falling , dizziness ( p and numbness of feet ( p = 0.017 ) and objective clinical measurement such as Timed Up and Go ( p = 0.002 ) and Romberg eyes closed ( p = 0.025 ) tests were all significantly impaired in long-term PPI users . Long-term PPI users were also more likely to have low vitamin B12 levels than non-users ( 50 % versus 21 % , p = 0.003 ) . In conclusion , similar to previous studies , we identified an increased fracture risk in subjects on long-term PPI therapy . This increase in fracture risk in elderly women , already at high risk of fracture , appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy" ]	41186e90-06ff-11f0-808a-c43d1ab1c353
Background . Most adults choose walking as a leisure activity . However , many do not reach the international physical activity guidelines for adults , which recommend moderate intensity aerobic activity for at least 150 minutes/week in bouts of 10 minutes . Purpose . This systematic review provides an up date on the walking cadence required to reach moderate intensity in adults and older adults , identifies variables associated with reaching moderate intensity , and evaluates how walking cadence intensity should be measured , but the main purpose is to report the interventions that have been attempted to prescribe walking cadence to increase time spent at moderate intensity or other outcomes for adults and older adults . Methods . SportD ISCUS , Scopus , and PubMed data bases were search ed . We identified 3,917 articles and 31 were retained for this systematic review . Only articles written in English were included . Results . In general , 100 steps/minute is prescribed for adults to achieve moderate intensity , but older adults may require a higher cadence . Currently , few studies have explored using walking cadence prescription as an intervention to increase physical activity levels . Conclusion . Prescribing walking cadence as a way to increase physical activity levels has potential as a practical and useful strategy , but more evidence is required to assess its ability to increase physical activity levels at moderate intensity	[ "Background Pedometer-based programs have elicited increased walking behaviors associated with improvements in blood pressure in sedentary/low active postmenopausal women , a population at increased risk of cardiovascular disease . Such programs typically encourage increasing the volume of physical activity with little regard for its intensity . Recent advances in commercially available pedometer technology now permit tracking of both steps/day and time in moderate ( or greater ) intensity physical activity on a daily basis . It is not known whether the dual message to increase steps/day while also increasing time spent at higher intensity walking will elicit additional improvements in blood pressure relative to a message to only focus on increasing steps/day . The purpose of this paper is to present the rationale , study design , and protocol s employed in WalkMore , a 3-arm 3-month blinded and r and omized controlled trial ( RCT ) design ed to compare the effects of two community pedometer-based walking interventions ( reflecting these separate and combined messages ) relative to a control group on blood pressure in sedentary/low active post-menopausal women , a population at increased risk of cardiovascular disease . Methods / Design 120 sedentary/low active post-menopausal women ( 45 - 74 years of age ) will be r and omly assigned ( computer-generated ) to 1 of 3 groups : A ) 10,000 steps/day ( with no guidance on walking intensity/speed/cadence ; BASIC intervention , n = 50 ) ; B ) 10,000 steps/day and at least 30 minutes in moderate intensity ( i.e. , a cadence of at least 100 steps/min ; ENHANCED intervention , n = 50 ) ; or a Control group ( n = 20 ) . An important strength of the study is the strict control and quantification of the pedometer-based physical activity interventions . The primary outcome is systolic blood pressure . Secondary outcomes include diastolic blood pressure , anthropometric measurements , fasting blood glucose and insulin , flow mediated dilation , gait speed , and accelerometer-determined physical activity and sedentary behavior . Discussion This study can make important contributions to our underst and ing of the relative benefits that walking volume and /or intensity may have on blood pressure in a population at risk of cardiovascular disease . Trial registration Clinical Trials.gov Record NCT01519583 , January 18 ,", "PURPOSE ( a ) To establish pedometer steps/min intensity categories ( i.e. , light , moderate , hard , very hard ) for adults under controlled conditions , and ( b ) use these cut-points to ascertain the number of steps expected in 30 minutes of moderate intensity activity . METHODS 25 men and 25 women , ages 18 - 39 years , performed 6-min exercise bouts at 3 treadmill speeds ( 4.8 , 6.4 , and 9.7 km/hr ) . Yamax SW-200 pedometers indicated steps , and steady-state VO2 was recorded . METs were calculated by dividing steady-state VO2 by 3.5 ml x kg(-1 ) x min(-1 ) . Linear regression was used to quantify the relationships between steps/min and METs across all speeds . Ten participants ( 5 M , 5 F ) were r and omly selected from the original 50 and constituted a holdout sample for cross-validation purpose s ( i.e , comparing actual and predicted METs ; paired t-test ) . RESULTS The regression equation for males was : METs = -7.065 + ( 0.105 x steps/min ) r2 = 0.803 . For females it was : METs = -8.805 + ( 0.110 x steps/min ) r2 = 0.830 . Cross-validation was confirmed . CONCLUSIONS Pedometer cut-points corresponding to minimal moderate intensity walking were 96 steps/min in men and 107 steps/min in women , or roughly 100 steps/min for both . This translates to approximately 3,000 steps in 30 min of moderate-intensity ambulatory activity for both genders", "BACKGROUND Increasing moderate-to-vigorous-intensity physical activity ( MVPA ) is an important public health goal . Pedometers are evidence -based devices for increasing daily activity , but studies have not evaluated the comparative efficacy of step cadence goals for increasing MVPA . PURPOSE This study aim ed to evaluate the efficacy of three pedometer-based step goals for increasing MVPA . METHODS Latina women ( n = 180 ; 18 - 55 yr , mean body mass index = 31.1 , SD = 6.5 ) were recruited to 12 community centers , which were r and omly assigned to one of three conditions . Each group received an identical 12-wk theory-based physical activity ( PA ) intervention that differed only on the type of daily step goal : 1 ) a self-selected goal ( SELF ) ; 2 ) a goal of 10,000 steps per day ( FREQUENCY ) ; or 3 ) a goal of 3000 steps in 30 min ( CADENCE ) . Accelerometer-based PA was measured at baseline and after 12 wk . RESULTS Adjusted multilevel pattern-mixture models using generalized estimating equations revealed that participants in the CADENCE condition engaged in similar levels of postintervention MVPA to those in the SELF and FREQUENCY goal conditions . However , MVPA of participants in the CADENCE condition was more likely to occur in bouts lasting greater than 10 consecutive minutes compared with the MVPA of participants in the SELF ( P = 0.01 ) or FREQUENCY ( P = 0001 ) conditions . CONCLUSIONS PA interventions should consider including a step cadence goal to help individuals accumulate bout-based MVPA and meet national PA guidelines", "Self-efficacy has a well-established , beneficial effect on health behavior and health status in young and middle-aged adults , but little is known about these relationships in older population s. We examined this issue as part of a r and omized trial to determine the cost savings and changes in health-related quality of life associated with the provision and reimbursement of a preventive services package to 2,524 Medicare beneficiaries enrolled in Group Health Cooperative of Puget Sound . Baseline self-efficacy data were collected for all participants in five behavioral areas : exercise , dietary fat intake , weight control , alcohol intake , and smoking . Results reveal that efficacy and outcome expectations for these health behaviors are not independent . Correlational and factor analyses indicate two dimensions of efficacy expectations , one consisting of exercise , dietary fat , and weight control , and another consisting of smoking and alcohol consumption . Outcome expectations of the five behaviors form a single dimension . Older adults with high self-efficacy had lower health risk in all behaviors and better health . Regression analyses detected a positive association between socioeconomic status and health-related quality of life ( p self-efficacy measures entered the model , indicating that self-efficacy explains part of the association between socioeconomic status and health status . Interventions aim ed at improving self-efficacy also may improve health status", "Recent public health recommendations for step frequency over a given timeframe ( steps min(-1 ) ) associated with moderate-intensity physical activity ( MPA ) have been developed . The recommendation suggests 100 steps min(-1 ) . This estimate overlooks the impact of anthropometric differences between individuals , notably leg length , which is related to step frequency . Therefore this study examined the impact of leg length on steps min(-1 ) associated with MPA . Twenty adults age 20 - 40 years ( age 26.4+/-4.6 years , 9 males ) walked over-ground at five walking speeds ( 0.5 m s(-1 ) , 0.75 m s(-1 ) , 1.0 m s(-1 ) , 1.25 m s(-1 ) , and 1.5 m s(-1 ) ) , lasting 6 min each , while wearing a portable gas analyser . Participants ' step frequency ( steps min(-1 ) ) for each walking speed was determined using a h and -tally counter . R and om effects models were used to predict steps min(-1 ) from METs and participant anthropometric measures ( body mass index and leg length [ cm ] ) . Model estimates were used to predict steps min(-1 ) corresponding to heights ranging from 5 ft . to 6 ft . 6 in . ( 6 in increments ) . Overall , 100 steps min(-1 ) corresponded to expending 3 METs ( SEE 3.49 steps min(-1 ) , R(2)=0.68 ) . As leg length increased estimated steps min(-1 ) decreased by -1.15 steps min(-1 ) ( 95CI -2.19 to -0.10 steps min(-1 ) ) . Based on leg length for individuals 5 ft to 6 ft 6 in . , steps min(-1 ) ranged from 111 to 85 , respectively . Established steps min(-1 ) cutpoints associated with MPA are general public health guidelines and anthropometric differences in leg length should be accounted for when developing step frequency recommendations for physical activity or weight loss studies that include individuals of varying height", "Purpose . Determine the proportion of adults aware of Canada 's Physical Activity Guide to Healthy Active Living ( Guide ) and its specific recommendations ( objective 1 ) ; whether key demographic factors ( objective 2a ) and physical activity behavior ( objective 2b ) are associated with awareness and specific familiarity with the Guide ; and if changes in awareness and specific recommendations with the Guide occurred over a 1-year period ( objective 3a and 3b ) . Design . R and om selection with computer-assisted telephone interviewing . Setting . Edmonton , Alberta , Canada . Subjects . A total of 2803 adults 18 years or older completed interviews from 4831 telephone contacts ( response rate , 58.0 % ) , and after 1 year , 1423 individuals ( 55 % ) completed interviews . Measures . Demographic , physical activity , Guide awareness . Analysis . Chi-square , analysis of variance . Results . At baseline , 27.3 % were aware of the Guide , and 15.6 % were familiar with the Guide 's specific recommendations . Younger individuals ( p = .01 ) , women ( p those with a higher education ( p aware of the Guide , and women were also more specifically aware ( p = .01 ) . Physical activity levels were positively associated with the general ( p awareness of the Guide . Changes in general familiarity and specific recommendations over 1 year were observed . Conclusions . The majority of those surveyed were not familiar with the Guide . Men , individuals with a lower education , and older individuals may need to be specifically targeted . ( Am J Health Promot 2011;25[5]:294 - 297 .", "PURPOSE The study investigated ( a ) walking intensity ( stride rate and energy expenditure ) under three speed instructions ; ( b ) associations between stride rate , age , height , and walking intensity ; and ( c ) synchronization between stride rate and music tempo during overground walking in a population of healthy older adults . METHODS Twenty-nine participants completed 3 treadmill-walking trials and 3 overground-walking trials at 3 self-selected speeds . Treadmill VO2 was measured using indirect calorimetry . Stride rate and music tempo were recorded during overground-walking trials . RESULTS Mean stride rate exceeded minimum thresholds for moderate to vigorous physical activity ( MVPA ) under slow ( 111.41 ± 11.93 ) , medium ( 118.17 ± 11.43 ) , and fast ( 123.79 ± 11.61 ) instructions . A multilevel model showed that stride rate , age , and height have a significant effect ( p Healthy older adults achieve MVPA with stride rates that fall below published minima for MVPA . Stride rate , age , and height are significant predictors of energy expenditure in this population . Music can be a useful way to guide walking cadence", "OBJECTIVES The purpose was to determine if a 12-week weight loss intervention with a physical activity ( PA ) component would lead to changes in steps/day , step count accumulation patterns , and peak cadence . DESIGN R and omized clinical trial . METHODS Overall , 121 overweight/obese White and African-American adults ( ages 35 - 64yrs ) were r and omized to a diet education plus PA education and behavior change intervention group ( DE+PA ) or diet education and behavior change group ( DE ) . The DE+PA intervention was design ed to increase steps/day , and steps at moderate-to-vigorous intensity . The Actigraph GT3X+ accelerometer was used to measure steps accumulated in different cadence b and s ( 1 - 19 , 20 - 39 , 40 - 59 , 60 - 79 , 80 - 99 , 100 - 119 , 120 + steps/min ) , and peak 1-min , 30-min and 60-min cadence . Pre- to post-intervention changes in steps/day , step count within each cadence b and , and peak cadences were compared within groups using paired sample t-test and between groups after adjustment for baseline values of the same variable using ANCOVA . RESULTS Ninety participants had valid data ( 44 in the DE+PA group ) . Change in steps/day was not significantly different between the groups . However , participants in the DE+PA group accumulated significantly more steps at post-intervention in the 80 - 99 , 100 - 119 , and 120 + cadence b and s , all p The DE+PA group increased step counts accumulated within the 100 - 119 ( 463±1092 vs 56±546 step counts ; p=0.01 ) and 120 + ( 390±999 vs 34±321 step counts ; p=0.03 ) cadence b and s , as well as peak 60-min cadence when compared to the DE group . CONCLUSIONS Non-significant changes in steps/day following a PA intervention may mask changes in steps accumulated at moderate-to-vigorous intensity cadences", "OBJECTIVES To determine self-selected brisk walking pace in currently inactive adults and investigate the efficacy of rhythmic auditory stimuli to regulate moderate intensity walking . DESIGN A single- sample controlled laboratory design . METHODS Currently inactive adults ( N=25 ; 76 % female ; age=34±13yr ) completed a moderate intensity treadmill walking trial , during which cadence and steady-state O2 were measured . Participants then completed a 10-min self-paced \" brisk \" walk followed by a 10-min moderate-paced walk , prompted by a clip-on metronome matched to the treadmill cadence . Data were analyzed using RM t-test , Cohen 's d , Bl and -Altman plot , and one-way RM ANOVA . RESULTS Mean energy expenditure and cadence during the treadmill trial were 3.88±0.53METs and 114±8stepsmin(-1 ) . During self-paced brisk walking cadence was 124±8stepsmin(-1 ) . Cadence during metronome-paced walking was slower for all participants ( 114±8stepsmin(-1 ) ; p Bl and -Altman plots , 23 participants walked within ±3stepsmin(-1 ) of the metronome cadence , and the other 2 participants were within ±10stepsmin(-1 ) . There were no significant differences ( p>0.05 ) among the minute-by-minute cadences across the 10min of either condition . CONCLUSIONS Energy expenditure during 2.7 mph treadmill walking was higher than 3 METs . Inactive adults walk at a higher cadence during \" brisk \" walking , compared to walking at a metronome-guided moderate pace . While the natural walking pace of inactive adults was at an intensity known to produce health benefits , and was maintained for 10min , the use of rhythmic auditory feedback is an effective method for regulating walking at a prescribed intensity in inactive adults", "UNLABELLED Current physical activity guidelines recommend physical activity of at least moderate intensity to gain health benefits . Previous studies have recommended a moderate-intensity walking cadence of 100 steps per minute for adults , but the influence of height or stride length has not been investigated . PURPOSE the purpose of the current study was to determine the role of height and stride length in moderate-intensity walking cadence in adults . METHODS seventy-five adults completed three treadmill walking trials and three overground walking trials at slow , medium , and fast walking speeds while V˙O2 was measured using indirect calorimetry . Five stride length-related variables were also measured . RESULTS mixed model regression analysis demonstrated that height explained as much variability in walking intensity at a given cadence as did two different measures of leg length and two different stride length tests . CONCLUSIONS the previous general recommendations of 100 steps per minute were supported for use where a simple public health message is needed . Depending on height , moderate-intensity walking cadence can vary by more than 20 steps per minute , from 90 to 113 steps per minute for adults 198 to 152 cm tall , respectively . Height should therefore be taken into consideration for more precise evaluation or prescription of walking cadence in adults to provide health benefits" ]	41186ecc-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Paroxetine is the most potent inhibitor of the reuptake of serotonin of all selective serotonin reuptake inhibitors ( SSRIs ) and has been studied in many r and omised controlled trials ( RCTs ) . However , these comparative studies provided contrasting findings and systematic review s of RCTs have always considered the SSRIs as a group , and evidence applicable to this group of drugs might not be applicable to paroxetine alone . The present systematic review assessed the efficacy and tolerability profile of paroxetine in comparison with tricyclics ( TCAs ) , SSRIs and newer or non-conventional agents . OBJECTIVES 1 . To determine the efficacy of paroxetine in comparison with other anti-depressive agents in alleviating the acute symptoms of Major Depressive Disorder.2 . To review acceptability of treatment with paroxetine in comparison with other anti-depressive agents.3 . To investigate the adverse effects of paroxetine in comparison with other anti-depressive agents . SEARCH METHODS We search ed the Cochrane Depression , Anxiety and Neurosis Review Group 's Specialized Register ( CCDANCTR , to 30 September 2012 ) , which includes relevant r and omised controlled trials from the following bibliographic data bases : The Cochrane Library ( all years ) , EMBASE ( 1974 to date ) , MEDLINE ( 1950 to date ) and PsycINFO ( 1967 to date ) . Reference lists of relevant papers and previous systematic review s were h and search ed . Pharmaceutical companies marketing paroxetine and experts in this field were contacted for supplemental data . SELECTION CRITERIA All r and omised controlled trials allocating participants with major depression to paroxetine versus any other antidepressants ( ADs ) , both conventional ( such as TCAs , SSRIs ) and newer or non-conventional ( such as hypericum ) . For trials which had a cross-over design , only results from the first r and omisation period were considered . DATA COLLECTION AND ANALYSIS Two review authors independently checked eligibility and extracted data using a st and ard form . Data were then entered in RevMan 5.2 with a double-entry procedure . Information extracted included study and participant characteristics , intervention details , setting s and efficacy , acceptability and tolerability measures . MAIN RESULTS A total of 115 r and omised controlled trials ( 26,134 participants ) were included . In 54 studies paroxetine was compared with older ADs , in 21 studies with another SSRI , and in 40 studies with a newer or non-conventional antidepressant other than SSRIs . For the primary outcome ( patients who responded to treatment ) , paroxetine was more effective than reboxetine at increasing patients who responded early to treatment ( Odds Ratio ( OR ) : 0.66 , 95 % Confidence Interval ( CI ) 0.50 to 0.87 , number needed to treat to provide benefit ( NNTb ) = 16 , 95 % CI 10 to 50 , at one to four weeks , 3 RCTs , 1375 participants , moderate quality of evidence ) , and less effective than mirtazapine ( OR : 2.39 , 95 % CI 1.42 to 4.02 , NNTb = 8 , 95 % CI 5 to 14 , at one to four weeks , 3 RCTs , 726 participants , moderate quality of evidence ) . Paroxetine was less effective than citalopram in improving response to treatment ( OR : 1.54 , 95 % CI 1.04 to 2.28 , NNTb = 9 , 95 % CI 5 to 102 , at six to 12 weeks , 1 RCT , 406 participants , moderate quality of evidence ) . We found no clear evidence that paroxetine was more or less effective compared with other antidepressants at increasing response to treatment at acute ( six to 12 weeks ) , early ( one to four weeks ) , or longer term follow-up ( four to six months ) . Paroxetine was associated with a lower rate of adverse events than amitriptyline , imipramine and older ADs as a class , but was less well tolerated than agomelatine and hypericum . Included studies were generally at unclear or high risk of bias due to poor reporting of allocation concealment and blinding of outcome assessment , and incomplete reporting of outcomes . AUTHORS ' CONCLUSIONS Some possibly clinical ly meaningful differences between paroxetine and other ADs exist , but no definitive conclusions can be drawn from these findings . In terms of response , there was a moderate quality of evidence that citalopram was better than paroxetine in the acute phase ( six to 12 weeks ) , although only one study contributed data . In terms of early response to treatment ( one to four weeks ) there was moderate quality of evidence that mirtazapine was better than paroxetine and that paroxetine was better than reboxetine . However there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any time point . Even if some differences were identified , the findings from this review are better thought as hypothesis forming rather than hypothesis testing and it would be reassuring to see the conclusions replicated in future trials . Finally , most of included studies were at unclear or high risk of bias , and were sponsored by the drug industry . The potential for overestimation of treatment effect due to sponsorship bias should be borne in mind	[ "An open-label , non-r and omized , pilot study has been performed in in patients in need of treatment with an antipsychotic ( risperidone ) and an antidepressant ( mirtazapine ) with the objective to preliminarily assess a possible pharmacokinetic interaction and the tolerability of this combination . A 1 - 4-week single drug treatment phase ( risperidone 1 - 3 mg bid or mirtazapine 30 mg nocte ) was followed by a 2 - 4-week combined drug treatment phase at unchanged doses . Twelve patients were enrolled , nine of whom were treated with risperidone in the single drug phase . Results of plasma level measurements are available for six patients and indicate that adding mirtazapine to risperidone does not alter steady-state plasma concentrations of risperidone and its 9-hydroxy metabolite . Data from one patient suggest that adding risperidone to mirtazapine does not result in clinical ly relevant changes in plasma concentrations of either compound . The combination was well tolerated and no major or relevant adverse events were observed . Adding risperidone to mirtazapine probably does not necessitate a change of the dosage of either drug , but more extensive investigations are needed", "INTRODUCTION The temporal course of recovery of depressed patients ' cognitive impairment is not fully understood . METHODS We used the California Verbal Learning Test ( CVLT ) to test declarative memory in 24 depressed patients before and after 35 days of antidepressive treatment as well as after long-term follow-up ( > 12 months ) in order to relate improvement of depression to recovery of cognitive impairment . RESULTS Patients with complete remission after 35 days had generally been less impaired at baseline . The disturbance of declarative memory in treatment responders as well as in non-responders did not change from baseline to end of treatment ( day 35 ) . However , our results revealed normal values in the CVLT sum score as well as in measures of short- and long-delay free-recall measures in both groups after long-term full remission . DISCUSSION We conclude that clinical response to antidepressive treatment precedes improvement of declarative memory . A low degree of impairment of declarative memory is associated with early complete remission of depression", "CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data", "This study was aim ed at resolving the time course of clinical action of antidepressants ( ADs ) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients . The first goal was to identify , during the first 2 weeks of treatment , the onset of clinical actions of the selective serotonin reuptake inhibitor ( SSRI ) , paroxetine , and the selective noradrenergic reuptake inhibitor , desipramine ( DMI ) . The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients . The design was a r and omized , parallel group , placebo-controlled , double-blind study for 6 weeks of treatment following a 1-week washout period . The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity . The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days , averaged 13 days for paroxetine , and was 16–42 days for placebo . Furthermore , as hypothesized , the different types of ADs initially impacted different behavioral aspects of the disorder . After 1 week of treatment , DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo , and this difference persisted at the second week of treatment . Early improvement in depressed mood – motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not . Paroxetine initially reduced anxiety more in responders than in nonresponders , and by the second week , significantly improved depressed mood and distressed expression in responders to a greater extent . Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement . Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs , results that could eventually be applied directly to clinical practice", "The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties . Like clinical ly used antidepressant and anxiolytic drugs , substance P antagonists suppressed isolation-induced vocalizations in guinea pigs . In a placebo-controlled trial in patients with moderate to severe major depression , robust antidepressant effects of the substance P antagonist MK-869 were consistently observed . In pre clinical studies , substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs . These findings suggest that substance P may play an important role in psychiatric disorders", "& NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine 30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors", "Christiansen PE , Behnke K , Black CH , Öhrström JK , Bork‐Rasmussen H , Nilsson J. Paroxetine and amitriptyline in the treatment of depression in general practice . Acta Psychiatr Sc and 1996 : 93 : 158–163 . © Munksgaard 1996", "OBJECTIVE Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder ( MDD ) . METHODS In this r and omized , double-blind trial , patients age > or = 18 meeting DSM-IV criteria for MDD were r and omized to placebo ( N=99 ) , duloxetine 80 mg/day ( N=93 ) , duloxetine 120 mg/day ( N=103 ) , or paroxetine 20 mg/day ( N=97 ) . The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression ( HAMD(17 ) ) total score after 8 weeks of treatment ; a number of secondary efficacy measures also were assessed . Safety and tolerability were assessed via collection and analysis of treatment-emergent adverse events ( TEAEs ) , vital signs , and weight . The Arizona sexual experiences scale was used to assess sexual functioning . Patients who had a > or = 30 % reduction from baseline in the HAMD(17 ) total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase ; efficacy and safety/tolerability outcomes were assessed during continuation treatment . RESULTS More than 87 % of patients completed the acute phase in each treatment group . Duloxetine-treated patients ( both doses ) showed significantly greater improvement ( P HAMD(17 ) total score at week 8 compared with placebo . Paroxetine was not significantly different from placebo ( P=0.089 ) on mean change on the HAMD(17 ) . Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures ( six of nine ) compared with placebo while duloxetine 80 mg/day ( three of nine ) and paroxetine ( three of nine ) were significantly superior to placebo on fewer secondary measures . HAMD(17 ) mean change data from this study and an identical sister study were pooled as defined a priori for the purpose s of performing a non-inferiority test versus paroxetine . Both duloxetine doses met statistical criteria for non-inferiority to paroxetine . TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases . CONCLUSIONS The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated . Tolerability , as measured by TEAEs , and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD", "In a double-blind clinical study , electrocardiogram , blood pressure and systolic time intervals were measured in 40 depressive patients treated with either paroxetine ( 30 mg/day ) or amitriptyline ( 150 mg/day ) for 6 weeks . While amitriptyline significantly increased the heart rate , the QTc interval and the PEP/LVET ratio , paroxetine did not alter any of the cardiovascular parameters measured", "OBJECTIVE Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase ( 8 weeks ) and an extension phase ( 16 weeks ) . METHODS Patients with major depression and without dementia , at least 65 years old , were eligible ; they were r and omized to mirtazapine or paroxetine once daily , with doses increasing over 42 days . Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale , and tolerability was assessed from adverse events . RESULTS Of 255 patients r and omized , 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis . Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score . Other significant differences were in the proportion of patients classified as responders ( 50 % decrease from baseline Ham-D-17 scores ) at Day 14 and in remission ( Ham-D-17 score of 7 or less ) at Day 42 . The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group . The mirtazapine group also showed more reduction in Ham-D Factor I ( Anxiety/Somatization ) and Factor VI ( Sleep Disturbance ) scores . Efficacy of both drugs was maintained during the extension phase . Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events . CONCLUSION During the first weeks of treatment , antidepressant effects were more pronounced in the mirtazapine group , suggesting that mirtazapine has an earlier onset of action . Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients", "These data provide evidence for the antidepressant efficacy of paroxetine . Paroxetine- and imipramine-treated patients were significantly different from placebo-treated patients , but little different to each other , on all depressive outcome measures . However , paroxetine appeared to have a possibly greater and earlier beneficial effect on anxiety symptoms associated with depression , when compared with imipramine . Both active therapies were effective in treating patients with severe depression . Side effects for paroxetine were typical of other serotonin ( 5-HT ) uptake inhibitors but different from those of imipramine . In particular , anticholinergic and cardiovascular symptoms were reduced , and premature withdrawal less likely", "BACKGROUND Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors . In a 12-week r and omized , multicenter , double-blind trial , the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression . METHODS A total of 203 patients were r and omized to fixed doses ( 20 mg/day ) of paroxetine or fluoxetine for the first six weeks of therapy . From week 7 - 12 , dosing could be adjusted biweekly , as required ( paroxetine 20 - 50 mg/day , and fluoxetine 20 - 80 mg/day ) . The mean prescribed doses were paroxetine 25.5 mg/day ( range 20.0 - 40.2 mg/day ) , and fluoxetine 27.5 mg/day ( range 20.0 - 59.5 mg/day ) . Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia . RESULTS Both active treatments demonstrated comparable antidepressant efficacy ( HAM-D , CGI ) . Anxiolytic activity of the two drugs ( COVI , STAI , HAM-D ) was also comparable . However , paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy ( HAM-D Agitation item , p incidence of adverse effects was comparable in the two treatment groups . Constipation , dyspepsia , tremor , sweating and abnormal ejaculation were more common in paroxetine-treated subjects , whereas nausea and nervousness were more frequent in fluoxetine-treated patients . Weight loss was more common in the fluoxetine versus paroxetine group ( 11.88 % versus 2.94 % , respectively ) . ESRS scores for akathisia were low throughout the study and showed little change . LIMITATIONS Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others . DISCUSSION The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy . Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine", "To compare the safety and antidepressant efficacy of paroxetine , imipramine , and placebo , data from six centres using the same protocol were pooled . A double-blind parallel-group design was used , with therapy lasting six weeks . From week 2 onwards , both the 240 paroxetine-treated and the 237 imipramine-treated patients were significantly different from the 240 placebo-treated patients , but no different from each other . Side-effects with paroxetine were less likely to lead to drop-out than with imipramine . Paroxetine had a possible earlier antidepressant effect than imipramine , and a possible earlier beneficial effect on anxiety symptoms associated with depression ", "Selective serotonin reuptake inhibitors ( SSRIs ) are widely used as effective pharmacological agents to treat depressive disorders . In contrast to the SSRIs , which block the presynaptic serotonin ( 5-HT ) transporter and by this route increase the concentration of serotonin in the synaptic cleft , the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission . Both SSRIs and tianeptine are clinical ly effective ; however , their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission . To better underst and the differences between these two opposite pharmacological modes of action , we compared the changes induced by tianeptine and paroxetine on psychopathology , the hypothalamic-pituitary-adrenocortical ( HPA ) system , and cognitive functions in a double-blind , r and omized , controlled trial including 44 depressed in patients over a period of 42 days . Depressive symptomatology significantly improved in all efficacy measures , with no significant differences between tianeptine and paroxetine . There was a trend toward better response to the SSRI among women . Assessment of the HPA system showed marked hyperactivity before the beginning of treatment , which then normalized in most of the patients , without significant differences between the two antidepressants . Cognitive assessment s showed no significant differences between the two drugs investigated . The results of the current study suggest that the initial effect , i.e. , enhancement or decrease of 5-HT release , is only indirectly responsible for antidepressant efficacy , and they support the notion that downstream adaptations within and between nerve cells are crucial . The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest", "The selective noradrenaline re-uptake inhibitor reboxetine may have advantages over the selective serotonin re-uptake inhibitors fluoxetine and citalopram , in effects on sexual function and satisfaction . The effects of reboxetine and paroxetine on sexual function were compared by examining data from the UK centres in an international double-blind flexible-dose parallel-group multi-centre r and omized controlled trial of acute treatment of patients with DSM-IV major depression . Patients were r and omly assigned to receive reboxetine ( 4 mg b.d . ) or paroxetine ( 20 mg mane ) using a double-dummy technique to preserve the blind . The dosage could be increased at day 28 ( to reboxetine 4 mg mane , 6 mg nocte ; or paroxetine 20 mg b.d . ) . Antidepressant efficacy was assessed by the 21-item Hamilton Rating Scale for Depression ( HAM-D ) and Clinical Global Impression Scale for Severity ( CGI-S ) at all study visits , and the Clinical Global Impression of Improvement ( CGI-I ) at each visit after r and omization . Sexual function and satisfaction was assessed by visual analogue scale ( VAS ) items of the Rush Sexual Inventory completed at baseline and days 28 and 56 . There were no significant differences between groups in demographic or clinical features at baseline . There was a gradual reduction in severity of depressive symptoms ( reboxetine , 14.3 ; paroxetine , 12.0 : observed case analysis ) , with no significant differences between groups . There were significant differences ( p 0.05 ) , with advantages for reboxetine , at Week 4 and Week 8 on the VAS item assessing ability to become sexually excited , and non-significant trends with advantages for reboxetine , in frequency of sexual thoughts at Week 4 ( p 0.05 ) and Week 8 ( p 0.08 ) ; and in desire to initiate sexual activity at Week 4 ( p 0.09 ) . Exclusion of patients who had ever experienced sexual dysfunction with any medication prior to participation in this study ( n 10 ) reduced the statistical significance of the findings , although there were still numerical advantages for reboxetine . Sexual function and satisfaction in depressed patients improves during double-blind acute treatment with reboxetine or paroxetine , but this improvement is greater and more rapid with reboxetine", "BACKGROUND About one-third of patients fail to respond to initial antidepressant therapy , which suggests a need for more effective drugs . AIMS To compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression . METHOD In- patients or out- patients satisfying DSM-III-R criteria for major depression in evolution for less than eight months , having a baseline HAM-D score > or = 18 and a HAM-D Item 3 score Doses were adjusted to 200 - 300 mg/day for venlafaxine and 30 - 40 mg/day for paroxetine . RESULTS For the observed-case analysis , the response rate was 51.9 % for venlafaxine and 32.7 % for paroxetine ( P = 0.044 ) , and a remission was achieved in 42.3 % of venlafaxine-treated and 20.0 % of paroxetine-treated patients ( P = 0.01 ) . The incidence of adverse effects was comparable between treatment groups . CONCLUSIONS Venlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population", " Fifty‐seven in patients with major depression ( DSM‐III‐R ) entered a 12‐week study comparing paroxetine and imipramine . Trends ( not reaching statistical significance ) in favour of paroxetine were seen on the Hamilton Depression Rating Scale ( HDRS ) and the Montgomery‐Åsberg Depression Rating Scale ( MADRS ) . The UKU Side Effect Rating Scale showed a significant difference in favour of paroxetine on reduced salivation . Global evaluation of side effect symptoms showed that significantly more paroxetine patients had no side effects , both in the investigators ’ and the patients ’ opinion . These results are in line with previous findings of paroxetine being an effective and well tolerated antidepressant", "In a 12‐week double‐blind study with 36 patients with major depressive episode ( DSM‐III ) , paroxetine ( Seroxat ® Aropax ® showed significantly quicker onset of efficacy on the Melancholia Scale , and better tolerance than imipramine . Plasma concentration analyses showed no clear concentration‐efficacy correlation in either treatment group . During long‐term treatment paroxetine seemed to be superior to imipramine in preventing relapse : both treatments were well tolerated . A significant correlation between baseline plasma tryptophan : large neutral amino acids ratio and final Hamilton Rating Scale for Depression ( HRSD ) score and a trend towards an inverse correlation between this ratio and percentage reduction in HRSD score were seen in the paroxetine group but not in the imipramine group . In line with previous studies , these results support the hypothesis that paroxetine is an effective and well tolerated antidepressant ", "BACKGROUND Milnacipran is a dual-action antidepressant which inhibits both serotonin and noradrenaline reuptake with no affinity for any neurotransmitter receptor studied . METHODS A 6-week double-blind multicentre study compared milnacipran ( 100 mg/day ) with paroxetine ( 20 mg/day ) in 300 out patients with major depression . Efficacy was evaluated using HAMD17 , MADRS and CGI for severity of illness and global improvement . Data were analysed on an intention to treat , last observation carried forward , basis . RESULTS Milnacipran and paroxetine were both effective and well tolerated with no significant difference in their effects . After treatment discontinuation , milnacipran was associated with significantly less emergent symptoms . Responders , at endpoint , to milnacipran had significantly greater levels of psychomotor retardation at baseline than non-responders . LIMITATIONS The study did not include a placebo group so that it is impossible to determine absolute levels of efficacy . CONCLUSIONS Both milnacipran and paroxetine were effective and well tolerated by out patients with major depression treated for 6 weeks . After treatment discontinuation milnacipran was associated with less emergent symptoms . Psychomotor retardation at baseline may be a predictive factor of a favourable response to milnacipran", "A comparative double-blind study of paroxetine and amitriptyline in the treatment of depressed hospital out patients was undertaken at 15 centres in Italy . Three hundred and nine patients of either sex were admitted to the study . The starting dose of paroxetine was 20 mg daily and of amitriptyline 75 mg daily in divided doses ; at week 3 these doses could be increased at the investigators ' discretion . Efficacy was measured on the Hamilton Depression Rating Scale and on Clinical Global Impression . Both treatment groups showed significant improvement at week 6 with no significant between-group differences . Significantly fewer patients receiving paroxetine reported adverse events compared with those on amitriptyline ( 44 % vs 62 % ; p paroxetine ) ", "OBJECTIVE To compare the efficacy and tolerability of paroxetine ( a selective serotonin reuptake inhibitor ) with that of amitriptyline ( a tricyclic antidepressant ) in the treatment of depression in 191 patients with rheumatoid arthritis ( RA ) . METHODS A r and omized , double blind , double dummy , parallel group study . A placebo washout period of 3 - 7 days was followed by an 8 week active treatment phase during which patients received either paroxetine ( 20 - 40 mg daily ) or amitriptyline ( 75 - 150 mg daily ) . The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint . RESULTS Paroxetine was as effective as amitriptyline for the treatment of depression , with similar improvements in RA associated pain and disability also seen in both groups . However , paroxetine was better tolerated than amitriptyline , with an overall frequency of adverse experiences of 56.4 % and 67.7 % in the 2 groups , respectively . The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group ( 18.1 % vs 43.8 % taking amitriptyline ) and paroxetine treated patients also experienced fewer severe ( 16.0 % vs 21.9 % ) , serious nonfatal ( 0 % vs 4.2 % ) , and drug related adverse experiences ( 12.8 % vs 29.2 % ) . CONCLUSION Tolerability is an important consideration in this patient population , which is largely composed of elderly patients who are taking additional medications for RA . Paroxetine shows a number of advantages in the management of depression comorbid with RA", "BACKGROUND This study aims to investigate the efficacy of fluoxetine and paroxetine on the levels of depression-anxiety , quality of life , disability , and metabolic control in type II diabetes mellitus ( DM ) patients . METHODS The patients were first applied the Hospital Anxiety-Depression Scale ( HADS ) . After a psychiatric interview with patients who had scores above the cut-off point , those who were diagnosed as having a major depressive disorder according to DSM-IV criteria were applied the Hamilton Depression Rating Scale ( HDRS ) and the Hamilton Anxiety Rating Scale ( HARS ) . Twenty three patients who scored 16 or above on the HDRS were included in the study and given the Short Form-36 ( SF-36 ) , and the Brief Disability Question naire ( BDQ ) and HbA1c levels were measured . Patients were r and omized on 20 mg/day fluoxetine or 20 mg/day paroxetine treatment . The patients were evaluated with the same scales at the 2(nd ) , 4(th ) , 6(th ) , and the 12(th ) weeks . RESULTS Both groups showed a statistically significant decrease in HDRS , HARS , and BDQ scores with comparison to the index assessment . At the end of treatment , though not statistically significant , a decrease was observed in HbA1c values of the fluoxetine-administered group . CONCLUSIONS Fluoxetine and paroxetine effectively reduce the severity of major depressive disorder in type II DM patients . There is need for further and longer-lasting monitoring studies with more patients in order to determine whether there is any difference in terms of their effects on glycemic control", "Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin ( Selective Serotonin Reuptake Inhibitors – SSRIs ) and noradrenaline ( Noradrenaline Reuptake Inhibitors – NaRIs ) into the presynaptic terminal . There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action . Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs , there are patients who respond to one class of compounds and not another . This suggests that treatment response could be predicted by genetic and /or clinical characteristics . Firstly , this study aims to investigate the influence of a polymorphism ( SLC6A4 ) in the 5HT transporter in altering response to SSRI medication . Secondly , the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs . Methods / design The GenPod trial is a multi-centre r and omised controlled trial . GPs referred patients aged between 18–74 years presenting with a new episode of depression , who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse . Patients were interviewed to ascertain their suitability for the study . Eligible participants ( with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory ( BDI ) score > 14 ) were r and omised to receive one of two antidepressant treatments , either the SSRI Citalopram or the NaRI Reboxetine , stratified according to severity . The final number r and omised to the trial was 601 . Follow-up assessment s took place at 2 , 6 and 12 weeks following r and omisation . Primary outcome was measured at 6 weeks by the BDI . Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments . Discussion The results of the trial will provide information about targeting antidepressant treatment for individual patients ; in turn this may increase prescribing efficacy , thereby speeding recovery and reducing the cost to the NHS . It will also help to underst and the different roles that noradrenaline and serotonin might play in the biology of depression . The trial is expected to report in the autumn of 2008.Trial Registration IS RCT N", "PURPOSE Clinical studies have suggested that venlafaxine induces a higher remission rate than paroxetine . However , very few studies have evaluated relapse episodes over treatment periods longer than a few weeks , and the cut-off score of 7 on the Hamilton Rating Scale for Depression ( HRSD ) often used to define remission is too high . This score is associated with the high rates of social function impairment . We report on a single centre , open-label , prospect i ve 24-week study to investigate the comparative efficacy of acute treatments with venlafaxine and paroxetine , using different definitions of response and remission rates . METHODS Out patients satisfying DSM-IV criteria for major depression with a baseline HRSD17 score of at least 16 were eligible . Following baseline evaluations , the patients were assigned to receive venlafaxine 75 - 225 mg/day with the mean dosage 141.35 + /- 26.98 ( SD ) mg/day ( n = 78 ) , or paroxetine 20 mg/day ( n = 92 ) for 24 weeks . Efficacy was assessed using the mean change in HRSD(17 ) score from baseline , the response rate and the remission rates based on different criteria for remission ( HRSD(17 ) score One hundred and seventy patients were evaluated for efficacy ; 78 treated with venlafaxine and 92 with paroxetine . Over the treatment period , venlafaxine was comparable with paroxetine on most outcome measures , whereas paroxetine produced significantly higher remission rates at weeks 4 , 8 , 16 , 20 and 24 weeks when the lower cutoff of 5 was used . CONCLUSIONS Venlafaxine treatment was similar to paroxetine according to the typical efficacy measures for treating out patients with major depression . However , based on the stricter remission criterion , paroxetine might be superior to venlafaxine", "BACKGROUND The efficacy , safety , and tolerance of nefazodone and paroxetine in the treatment of depressed out patients were compared in a r and omized , double-blind parallel group study at 20 centers in the United Kingdom and Republic of Irel and . METHOD The study population comprised 206 out patients meeting DSM-III-R criteria for a moderate-to-severe nonpsychotic major depressive episode . Patients considered to be at serious risk of suicide were excluded from participation in the study . After a drug-free baseline phase of 1 to 4 weeks , patients were r and omly assigned to treatment with either nefazodone or paroxetine . Outcome measures for efficacy included the Clinical Global Impressions scales , Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , Montgomery-Asberg Depression Rating Scale , and Patient Global Assessment scale . Tolerance and safety were assessed using spontaneously reported adverse events , vital signs , and laboratory investigations . RESULTS There were no significant differences between the groups in clinical outcome . Analysis of the efficacy measures revealed a consistent and continuous improvement in both groups . A similar proportion of patients in each group discontinued treatment owing to adverse events : 15 ( 14 % ) in the nefazodone group and 13 ( 13 % ) in the paroxetine group . CONCLUSION Nefazodone and paroxetine have similar efficacy and tolerability in the treatment of out patients with major depression", "Impaired cognitive functioning is often associated with major depressive disorder ( MDD ) . Moreover , a number of agents used to treat MDD are known to have negative effects on cognitive functioning . We report an assessment of the effects of the selective norepinephrine reuptake inhibitor reboxetine , the selective serotonin reuptake inhibitor paroxetine , and placebo on a variety of measures of cognitive functioning in patients with MDD.Cognitive functioning in 74 adult patients ( aged 18–65 years ) with a confirmed diagnosis of MDD ( DSM-IV ) was assessed as part of two identical , r and omized , double-blind , placebo- and active-treatment-controlled , fixed/flexible dose comparisons of 8 weeks of treatment with reboxetine ( 8–10 mg/day ) , paroxetine ( 20–40 mg/day ) and placebo . Cognitive function was assessed at baseline , day 14 and day 56 using a selection of tasks from the Cognitive Drug Research computerized assessment system , including Simple Reaction Time , Digit Vigilance , Choice Reaction Time , Numeric Working Memory , Word Recognition and Critical Flicker Frequency . The results in the 74 patients ( reboxetine n = 25 , paroxetine n = 23 , placebo n = 26 ) showed that reboxetine significantly improved the ability to sustain attention at day 56 compared with baseline ( P = 0.023 ) . In addition , patients who received reboxetine experienced significant improvements in their speed of cognitive functioning when tested at day 56 compared to baseline ( P = 0.024 ) . No significant changes or trends in this direction were seen among patients who received either placebo or paroxetine . The results of the present study provide objective data to support the possibility that reboxetine favourably affects cognitive processes in depressed patients", "BACKGROUND Duloxetine is a balanced and potent dual reuptake inhibitor of serotonin ( 5-HT ) and norepinephrine ( NE ) that has previously been shown to be effective in the acute treatment of major depressive disorder ( MDD ) . This placebo-controlled study assesses the safety and efficacy of duloxetine ( 80 or 120 mg/day ) and paroxetine ( 20 mg QD ) during an initial 8-week acute phase and subsequent 6-month continuation phase treatment of MDD . METHOD In this r and omized , double-blind , placebo-controlled trial , adult out patients ( age > or= 18 years ) meeting DSM-IV criteria for MDD received placebo ( n = 93 ) , duloxetine 80 mg/day ( 40 mg BID ; n = 95 ) , duloxetine 120 mg/day ( 60 mg BID ; n = 93 ) , or paroxetine ( 20 mg QD ; n = 86 ) for 8 weeks . Patients who had a > or= 30 % reduction from baseline in HAMD(17 ) total score during the acute phase were allowed to continue on the same ( blinded ) treatment for a 6-month continuation phase . Efficacy measures included the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) total score , HAMD(17 ) subscales , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Hamilton Anxiety Rating Scale ( HAMA ) , Visual Analog Scales ( VAS ) for pain , the Clinical Global Impression of Severity ( CGI-S ) and Patient Global Impression of Improvement ( PGI-I ) scales , the 28-item Somatic Symptom Inventory ( SSI ) , and the Sheehan Disability Scale ( SDS ) . Safety and tolerability were assessed using treatment-emergent adverse events , discontinuations due to adverse events , vital signs , ECGs , laboratory tests , and the Arizona Sexual Experiences Scale ( ASEX ) . RESULTS During the acute phase , patients receiving duloxetine 80 mg/day , duloxetine 120 mg/day , or paroxetine 20 mg QD had significantly greater reductions in HAMD(17 ) total score compared with placebo . Both duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups had significantly greater improvement , compared with placebo , in MADRS , HAMA , CGI-S , and PGI-I scales . Estimated probabilities of remission at week 8 for patients receiving duloxetine 80 mg/day ( 51 % ) , duloxetine 120 mg/day ( 58 % ) , and paroxetine ( 47 % ) were significantly greater compared with those receiving placebo ( 30 % ) . The rate of discontinuation due to adverse events among duloxetine-treated patients ( 80 and 120 mg/day ) did not differ significantly from the rate in the placebo group . Treatment-emergent adverse events reported significantly more frequently by duloxetine-treated patients than by patients receiving placebo were constipation ( 80 and 120 mg/day ) , increased sweating ( 120 mg/day ) , and somnolence ( 120 mg/day ) . The incidence of acute treatment-emergent sexual dysfunction in duloxetine- and paroxetine-treated patients was 46.5 % and 62.8 % , respectively . During the 6-month continuation phase , duloxetine ( 80 and 120 mg/day ) and paroxetine treatment groups demonstrated significant improvement in HAMD(17 ) total score . Treatment-emergent adverse events occurring most frequently in each active treatment group during the continuation phase were viral infection ( duloxetine 80 mg/day ) , diarrhea ( duloxetine 120 mg/day ) , and headache ( paroxetine 20 mg QD ) . CONCLUSION These data support previous findings that duloxetine is safe , efficacious , and well tolerated in the acute treatment of MDD . Furthermore , these data provide the first demonstration under double-blind , placebo-controlled conditions that the efficacy and tolerability of duloxetine are maintained during chronic treatment", "A total of 101 patients entered a double-blind , parallel-group study in general practice , comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients . All patients received placebo for 1 week followed by active therapy for a total of 6 weeks . Medication was r and omly allocated , two-thirds of the patients took paroxetine ( 20 mg daily ) and one-third received amitriptyline ( 50 mg daily ) ; this dose was increased to 30 mg and 100 mg , respectively , after 1 week . Of the patients who entered the placebo run-in , 90 took active treatment and were evaluable on an intention-to-treat basis ( 56 paroxetine , 32 amitriptyline ) . The mean age of the patients was 72 years . Significant reductions in Hamilton Depression Rating Scale ( HAMD ) from baseline to the end of treatment were seen for both groups ( p HAMD score was reduced by half , or more , for 76 % of patients taking paroxetine and 86 % taking amitriptyline . Significant improvement was observed in the investigators ' Clinical Global Impression ( CGI ) score for 57 % of patients taking paroxetine and 52 % on amitriptyline . Improvements after treatment were also observed in the Leeds Sleep Evaluation Question naire ( LSEQ ) scores . Significantly fewer patients taking paroxetine reported adverse events ( 34 % vs 63 % taking amitriptyline , p = 0.02 ) . Those taking paroxetine experienced significantly fewer anticholinergic side effects ( 7 % vs 25 % taking amitriptyline , p = 0.04 ) . Overall , this study confirmed the effectiveness of paroxetine as an antidepressant drug . The relatively low incidence of adverse events , compared with amitriptyline , particularly the anticholinergic side effects which may be associated with disturbances in cognitive function , makes paroxetine suitable for the treatment of elderly depressed patients in general practice", "ABSTRACT Objectives : To evaluate the efficacy and safety of trazodone prolonged release compared with paroxetine in the treatment of patients with major depression . Research design and methods : A total of 108 patients aged 20–68 years were enrolled in this multicentre , double-blind , double-dummy , r and omised , paroxetine-controlled study . Each patient received 3 days single-blind placebo treatment followed by 6 weeks double-blind treatment with either trazodone prolonged release 150–450 mg/day ( n = 55 ) or paroxetine 20–40 mg/day ( n = 53 ) . Outcome measures : Efficacy was evaluated by the rate of patients responding to each treatment and considered to be in remission , and by mean changes from baseline in the Hamilton Depression Rating scale scores ( HAM-D ) , Montgomery Asberg Depression Rating Scale scores ( MADRS ) , and Clinical Global Impression ( CGI ) – Severity and Global Improvement scores . Time to onset of efficacy and safety were assessed . Results : Trazodone and paroxetine were equally effective at reducing symptoms of depression and promoting remission . Onset of efficacy was slightly faster for patients treated with paroxetine . Overall , there were no significant differences between the groups at endpoint in efficacy measures , and in percentage of responders ( > 85 % ) or patients in remission ( > 65 % ) . Sleep disorders ( HAM-D subset ) were significantly less evident for patients in the trazodone group at the end of the study ( p . Adverse drug reactions were reported by 35 % of trazodone-treated patients ( mainly of the nervous system ) and 26 % of paroxetine-treated patients ( mainly gastrointestinal ) , although none was considered to be serious . Conclusions : This study showed that after a 6-week period trazodone and paroxetine are not different in reducing the symptoms of depression and , in many patients , in producing the remission of the illness . The known divergence in tolerability profile of the two medications , related to their differing pharmacological properties , was also confirmed . Trazodone may be of advantage in depressed patients with sleep difficulties", "Abstract Objective To investigate the efficacy of hypericum extract WS 5570 ( St John 's wort ) compared with paroxetine in patients with moderate to severe major depression . Design R and omised double blind , double dummy , reference controlled , multicentre non-inferiority trial . Setting 21 psychiatric primary care practice s in Germany . Participants 251 adult out patients with acute major depression with total score ≥ 22 on the 17 item Hamilton depression scale . Interventions 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks . In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks . Main outcome measures Change in score on Hamilton depression scale from baseline to day 42 ( primary outcome ) . Secondary measures were change in scores on Montgomery-Åsberg depression rating scale , clinical global impressions , and Beck depression inventory . Results The Hamilton depression total score decreased by mean 14.4 ( SD 8.8 ) points , corresponding to 56.6 % ( SD 34.3 % ) of the baseline value , in the hypericum group and by 11.4 ( SD 8.6 ) points ( 44.8 % ( SD 33.5 % ) of baseline value ) in the paroxetine group ( intention to treat analysis ; similar results were observed in the per protocol analysis ) . The intention to treat analysis ( lower one sided 97.5 % confidence limit 1.5 points for the difference hypericum minus paroxetine ) and the per protocol analysis ( lower confidence limit 0.7 points ) showed non-inferiority of hypericum and statistical superiority over paroxetine . The lower limits in both cases exceeded the pre-specified non-inferiority margin of −2.5 points and the superiority margin of 0 . The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine , respectively . Conclusions In the treatment of moderate to severe major depression , hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated", "A 6-week double-blind , parallel group study compared paroxetine and fluoxetine in 106 depressed geriatric in patients ( aged 65 to 85 years ) . Patients presenting acutely with major depressive episode DSM-III-R 296.2 ( HAMD > 18 on 21 item scale ) were r and omized to receive paroxetine ( 20 - 40 mg , n = 54 ) or fluoxetine ( 20 - 60 mg , n = 52 ) following a 3 - 7 day washout . Primary criteria was the reduction of Hamilton Depression Rating Scale Score ( HAMD ) . Furthermore Montgomery-Asberg Depression Rating Scale ( MADRS ) and the Clinical Global Impression Scale ( CGI ) were used . Cognitive functions were assessed with the Mini-Mental-State Examination ( MMSE ) and the S and oz Clinical Assessment Geriatric Scale ( SCAG ) . The results showed a comparable reduction in the depression rating scales between the two treatment groups after 6 weeks . However , there was a statistically significant difference ( p HAMD , MADRS , SCAG , MMSE and cognitive subscales of HAMD and SCAG at week 3 in favour of paroxetine , which even was seen after 6 weeks in the SCAG . There were no significant differences between the treatment groups and the number of adverse events reported or in overall tolerability", "Objective : This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice . Methods : In this double-blind , multicentre study conducted in the general practice , patients with depression ( Montgomery Asberg Depression Rating Scale [ MADRS ] score ≥ 20 ) who were regarded as requiring antidepressant therapy were r and omly assigned to receive paroxetine ( 20 mg , n=184 ) or amitriptyline ( 50–100 mg , n=191 ) once daily for 9 weeks . Results : More patients completed treatment with paroxetine than with amitriptyline ( 71.1 % vs 56.1 % , p=0.009 ) . Depression rating scores ( MADRS and Clinical Global Impression [ CGI ] ) were improved with both agents , but at week 9 , paroxetine achieved more favourable scores compared with amitriptyline on MADRS ( p=0.019 ) , CGI severity of depression ( p=0.044 ) , and CGI efficacy index ( p=0.038 ) . Conclusions : Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline ", "ABSTRACT Objective : This r and omised , double-blind , fixed-dose study evaluated the efficacy of escitalopram and paroxetine in the long-term treatment of severely depressed patients with major depressive disorder ( MDD ) . Research design and methods : Patients with a primary diagnosis of MDD and baseline Montgomery-Åsberg Depression Rating Scale ( MADRS ) ≥ 30 were r and omised to 24 weeks of double-blind treatment with fixed doses of either escitalopram ( 20 mg ) ( n = 232 ) or paroxetine ( 40 mg ) ( n = 227 ) . The primary analysis of efficacy was an analysis of covariance ( ANCOVA ) of change from baseline to endpoint ( Week 24 ) in MADRS total score ( last observation carried forward , LOCF ) . Main outcome measures ; results : At endpoint ( 24 weeks ) , the mean change from baseline in MADRS total score was –25.2 for patients treated with escitalopram ( n = 228 ) and –23.1 for patients with paroxetine ( n = 223 ) , result ing in a difference of 2.1 points ( p in the MADRS total score ( LOCF ) was significantly in favour of escitalopram from Week 8 onwards . The proportion of remitters ( MADRS ≤ 12 ) after 24 weeks was 75 % for escitalopram and 67 % for paroxetine ( p the primary efficacy scale were supported by significantly greater differences in favour of escitalopram on the Hamilton Anxiety , Hamilton Depression and Clinical Global Impression-Improvement and -Severity scales . For very severely depressed patients ( baseline MADRS ≥ 35 ) , there was a difference of 3.4 points at endpoint in the MADRS total score in favour of escitalopram ( p rate for patients treated with escitalopram ( 19 % ) was significantly lower than with paroxetine ( 32 % ) ( p events was significantly lower for escitalopram ( 8 % ) compared to paroxetine ( 16 % ) ( p incidence of individual adverse events during treatment . Conclusion : Escitalopram is significantly more effective than paroxetine in the long-term treatment of severely depressed patients", "BACKGROUND A large proportion of the elderly population complains of depressive symptoms . The ideal antidepressant for these patients , who often suffer from numerous concomitant diseases , should not worsen their cognitive functions and should be free of contraindications . METHOD To assess the effects of 2 selective serotonin reuptake inhibitors on cognitive functions in elderly depressed patients ( ICD-10 criteria ) , we conducted a double-blind , r and omized , parallel-group , multicenter study comparing paroxetine ( 20 - 40 mg daily ) and fluoxetine ( 20 - 60 mg daily ) treatment for 1 year . Cognitive performance was evaluated by means of the Buschke Selective Reminding Test , the Blessed Information and Memory Test , the Clifton Assessment Schedule , the Cancellation Task Test , and the Wechsler Paired Word Test ; the Hamilton Rating Scale for Depression ( HAM-D ) and the Clinical Anxiety Scale were administered to assess the course of depressive and anxiety symptoms , respectively . RESULTS 242 patients were enrolled ( mean + /- SD age = 75.4 + /- 6.6 years ) . During the study , no deterioration of cognition was observed ; on the contrary , most of the tested cognitive functions improved . Good antidepressant efficacy was maintained for over 1 year with both drugs , based on the percentage of responders to treatment ( patients achieving a HAM-D total score tolerability and safety profile . CONCLUSION The 2 antidepressants proved to be suitable for the long-term treatment of depression in the elderly and to be devoid of detrimental effects on the tested cognitive functions", "This study assessed whether fluoxetine , sertraline , and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes . Patients ( N = 284 ) with DSM-IV major depressive disorder were r and omly assigned in a double-blind fashion to fluoxetine , paroxetine , or sertraline for 10 to 16 weeks of treatment . Using the Hamilton Rating Scale for Depression ( HAM-D ) sleep disturbance factor score , patients were categorized into low ( high ( ≥4 ) baseline insomnia subgroups . Changes in depression and insomnia were assessed . Safety assessment s included treatment-emergent adverse events ( AEs ) , reasons for discontinuation , and AEs leading to discontinuation . In addition , AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation . Depression improvement , assessed with the HAM-D-17 total score , was similar among treatments in all patients ( p = 0.365 ) and the high ( p = 0.853 ) and low insomnia ( p = 0.415 ) subgroups . Insomnia improvement , assessed with the HAM-D sleep disturbance factor score , was similar among treatments in all patients ( p = 0.868 ) and in the high ( p = 0.852 ) and low insomnia ( p = 0.982 ) subgroups . Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening , any worsening , worsening at endpoint , or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup . Treatments were well tolerated in most patients . No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups . These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine , sertraline , and paroxetine in major depressive disorder patients . Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia", "The present study aim ed to compare the effects of two currently used selective serotonin reuptake inhibitors ( SSRIs ) in Japan taking the individual background in 5-HTT gene-linked polymorphic region ( 5HTTLPR ) genotype into account . Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression . Patients with the l allele had a greater percentage reduction on the total score ( P=0.059 ) and somatic anxiety items ( P=0.026 ) of the 21-item Hamilton Depression Rating Scale ( HAM-D ) score compared to s/s genotype carriers . Paroxetine was significantly more effective than fluvoxamine in the s/s carriers , as evaluated on the percentage reduction in total score ( P=0.012 ) and core ( P=0.049 ) HAM-D after 4 weeks of medication , but not in the l/s carriers . These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs , and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis", "Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness . We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS ( CDC stages 2B , 2C , 3B , or 3C ) in a 6 week open-label trial with sertraline , paroxetine , or fluoxetine , to assess their effectiveness and tolerability . We further assessed whether treatment of depression result ed in a reduction in both affective and somatic symptoms in this medically ill population . Twenty-four subjects ( 73 % ) completed the trial ( 7 on sertraline , 7 on paroxetine , 10 on fluoxetine ) , 20 ( 83 % ) of whom were clinical responders . Nine dropped out within 1 - 3 weeks of treatment because of adverse effects , mostly agitation , anxiety , and insomnia . Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms , many of the latter having been attributed to HIV rather than depression . These results suggest that , even in later stages of HIV illness , the contribution of depression to perceived somatic symptoms may be significant , and that these symptoms may improve with antidepressant treatment", "OBJECTIVE Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied . The extent and implication s of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated , to the authors ' knowledge . METHOD The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry , the Archives of General Psychiatry , the Journal of Clinical Psychopharmacology , and the Journal of Clinical Psychiatry between 2001 and 2003 . RESULTS Among 397 clinical trials identified , 239 ( 60 % ) reported receiving funding from a pharmaceutical company or other interested party , and 187 studies ( 47 % ) included at least one author with a reported financial conflict of interest . Among the 162 r and omized , double-blind , placebo-controlled studies examined , those that reported conflict of interest were 4.9 times more likely to report positive results ; this association was significant only among the subset of pharmaceutical industry-funded studies . CONCLUSIONS Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo", "Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors . The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine . However , most data were collected in sample s of out patients . To overcome this restriction , a six-week double-blind control-group study , comparing 30 mg paroxetine with 150 mg amitriptyline per day , was performed in a sample of in patients suffering from major depression . Generally speaking , the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline , either with respect to the total score on the Hamilton Depression Scale ( HAMD ) and the Clinical Global Impressions or with respect to the subscores of the HAMD . One exception was the retardation subscore , in which amitriptyline showed a greater degree of reduction . Both drugs had a characteristic side-effect profile . Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea", "BACKGROUND We assessed the therapeutic effects of venlafaxine XR and paroxetine on mood and anxiety symptoms derived from the tripartite model of mood . We hypothesized that the two antidepressants would have largely similar effects on symptoms of negative affect because both agents influence serotonergic systems . However , based on evidence indicating linkages between catecholaminergic activity and the emotional dimension of positive affect , we hypothesized that the catecholaminergic effects of venlafaxine XR would yield particularly pronounced effects on symptoms of positive affect . METHODS Twenty depressed out patients were r and omly assigned to treatment with either venlafaxine XR ( 225 mg/day ) or paroxetine ( 30 mg/day ) during a 12-week treatment trial . Weekly mood ratings were collected using the Mood and Anxiety Symptom Question naire [ Watson , D. , Clark , L.A. , Weber , K. , Assenheimer , J.S. , Strauss , M.E. , McCormick , R.A. , 1995 . Testing a tripartite model : II . Exploring the symptom structure of anxiety and depression in student , adult , and patient sample s. J. Abnorm . Psychol . 104 ( 1 ) , 15 - 25 ] [ Watson , D. , Weber , K. , Assenheimer , J.S. , Clark , L.A. , Strauss , M.E. , McCormick , R.A. , 1995 . Testing a tripartite model : I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales . J. Abnorm . Psychol . 104 ( 1 ) , 3 - 14 ] . RESULTS Consistent with predictions , analyses revealed that there were no significant differences between venlafaxine XR and paroxetine on measures of negative affect . However , contrary to predictions , the two medications produced similar changes on measures of positive affect . LIMITATIONS Replication and extension using a larger sample size are m and ated . CONCLUSIONS These preliminary results suggest that two antidepressants that appear to have dissimilar mechanisms of action may nevertheless have similar effects on the positive and negative affective components of depression . Alternatively , paroxetine may have a clinical ly relevant noradrenergic effect at the dose tested", "Paroxetine ( 30 mg ) , a selective serotonin ( 5-HT ) reuptake inhibitor , was compared in a double-blind trial to amitriptyline ( 150 mg ) in a sample of 40 in patients aged 18 - 65 years who fulfilled Research Diagnostic Criteria for major depression . Patients were studied after a placebo drug washout period of 10 days and after an active 4-week treatment period . Sleep EEG recordings were performed before and at the end of the study as well as during acute treatment ( first 2 days ) and following withdrawal of active medication . Paroxetine shows an antidepressant effect similar to amitriptyline with a different side-effect profile typical of 5-HT reuptake inhibition . Paroxetine and amitriptyline decreased the amount of REM sleep , a well-known effect of classical antidepressants . Paroxetine also shared with other 5-HT reuptake inhibitors an alerting effect on sleep that was not shown to be detrimental on subjective sleep quality", "This multinational , r and omized , double-blind , flexible-dose study evaluated the short- and long-term antidepressant tolerability and efficacy of escitalopram and paroxetine . Tolerability was assessed by monitoring adverse events throughout the study , and discontinuation events during brief treatment interruption and tapered withdrawal . Discontinuation-emergent effects were evaluated in two separate double-blind periods . First , to mimic the consequences of non-compliance , patients were r and omized to one of two treatment interruption periods ( placebo-substitution for 3–5 days ) . Second , patients were r and omized to a 1–2-week tapered withdrawal period r and omly scheduled between weeks 28 and 31 . The pre-specified primary efficacy endpoint was the mean change from baseline in total Montgomery – Åsberg Depression Rating Scale ( MADRS ) score at week 8 , using the principle of last observation carried forward . A total of 323 patients entered 8 weeks of double-blind treatment and received at least one flexible dose of escitalopram ( 10–20 mg/day ) or paroxetine ( 20–40 mg/day ) . Patients who demonstrated evidence of a significant clinical improvement ( Clinical Global Impression – Improvement of 1 or 2 ) at week 8 entered a 19-week , double-blind maintenance period during which they were treated with the same dose they received at week 8 , followed by a 1–2-week tapered withdrawal period . A total of 89 patients ( 28 % ) withdrew during the study ; significantly ( P paroxetine group ( 34 % ) than from the escitalopram group ( 21 % ) , and significantly ( P The mean MADRS total score improved for both treatment groups from baseline to week 8 , with no statistical difference between groups . In severely depressed patients ( baseline MADRS total score ≥30 ) , escitalopram was superior ( P of sexual dysfunction at baseline : the mean Arizona Sexual Experience Scale ( ASEX ) score was approximately 20 points in both treatment groups . Mean total ASEX scores increased slightly above baseline values during the acute period and declined slightly below baseline values towards the end of the maintenance period . During taper and cessation of treatment , patients in the paroxetine group demonstrated significantly more discontinuation symptoms relative to escitalopram based on the Discontinuation Emergent Signs and Symptoms scores", "The efficacy of paroxetine and fluoxetine and their effects on cognitive and behavioural function were compared in a 6 week , double-blind , r and omized study of 106 elderly depressed patients ( aged 61 to 85 years ) . Antidepressant efficacy was assessed using the Hamilton depression rating scale ( HAMD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) scale . The S and oz Clinical Assessment Geriatric scale ( SCAG ) , the Mini-Mental State Examination ( MMSE ) , and HAMD cognitive factor scores were used to assess cognitive and behavioural function . Paroxetine demonstrated comparable efficacy to fluoxetine in the treatment of elderly depressed patients , but at the end of treatment , there was a significantly higher proportion of responders to paroxetine than to fluoxetine . Both treatments produced improvements in all measures of cognitive and behavioural function , but paroxetine was significantly superior to fluoxetine from Week 3 , indicating a possible early effect . There was no difference between the two agents in either the tolerability or safety of treatment", "We report results from a multicenter , placebo-controlled , r and omized , double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in out patients with major depression . Across five U.S. sites , 128 out patients ( mean age : 41.3 + /- 12.6 ; 63 men and 65 women ) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994 . All 128 patients completed a 1-week placebo washout period , and were then r and omized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day ( n = 55 ) , fluoxetine up to 80 mg/day ( n = 54 ) , or placebo ( n = 19 ) . Subjects were evaluated weekly for the first 4 weeks , then at weeks 6 , 9 , and 12 with the 21-item HAMD and the Covi Anxiety Scale . There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity , as well as in the degree of depression and anxiety improvement . There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients . In summary , our results , although limited by the lack of a significant difference from placebo in treatment outcome , suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed out patients , as well as similar safety and tolerability profiles", "A total of 60 patients aged 65 years and over who were suffering from unipolar depression were entered into a double-blind 6-week comparative study of paroxetine and mianserin . Assessment s of efficacy of treatment included the Hamilton Depression Rating Scale . Clinical Global Impression , and the Leeds Sleep Evaluation Question naire . The results showed that the two drug had equal and acceptable clinical efficacy . There was a similar overall incidence of spontaneously reported adverse events , but with clearly different profiles and a suggestion that mianserin was associated with more anticholinergic effects . In terms of sleep , the study provided evidence of a more beneficial effect from paroxetine", "Depressive illness among the elderly is an important public health concern . However , treatment of the elderly may be complicated by age-related changes in physiology , general medical status , and susceptibility to side effects . There is therefore a need for improved treatment modalities for depressed elderly patients . Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake . It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants . The authors present the combined data from two similarly design ed comparisons of paroxetine and doxepin in out patients over 60 years of age with major depression . The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression ( HAM-D ) total score , the Montgomery and Asberg Depression Rating Scale ( MADRS ) , and the Hopkins Symptom Checklist ( SCL ) depression factor score . Paroxetine was significantly superior to doxepin on the Clinical Global Impressions ( CGI ) scale for severity of illness , the HAM-D retardation factor , and the HAM-D depressed mood item . Doxepin produced significantly more anticholinergic effects , sedation , and confusion . Paroxetine was associated with more reports of nausea and headache . These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly", "Paroxetine and venlafaxine are potent serotonin transporter ( SERT ) antagonists and weaker norepinephrine transporter ( NET ) antagonists . However , the relative magnitude of effect at each of these sites during treatment is unknown . Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition . Outpatient subjects ( N=86 ) meeting criteria for major depression were enrolled in a multicenter , 8 week , r and omized , double-blind , parallel group , antidepressant treatment study . Subjects were treated by forced-titration of paroxetine CR ( 12.5–75 mg/day ) or venlafaxine XR ( 75–375 mg/day ) over 8 weeks . Blood sample s were collected weekly to estimate transporter inhibition . Both medications produced dose-dependent inhibition of the SERT and NET . Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90 % ( SD 7 ) and 85 % ( SD 10 ) , respectively . Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36 % ( SD 19 ) and 60 % ( SD 13 ) , respectively . The adjusted mean change from baseline ( mean 28.6 ) at week 8 LOCF in MADRS total score was −16.7 ( SE 8.59 ) and −17.3 ( SE 8.99 ) for the paroxetine and venlafaxine-treated patients , respectively . The magnitudes of the antidepressant effects were not significantly different from each other ( 95%CI −3.42 , 4.54 , p=0.784 ) . The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo . NET antagonism has been posited to contribute to the antidepressant effects of these compounds . The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present", "Even though r and omised controlled trials are the design of choice for evaluating the efficacy of health care interventions , they are not immune to bias that may affect research process and validity of results . In the present paper we discussed how trial quality may be appraised considering both whether a clinical trial is reported in a comprehensive and complete way ( consistently with what had been declared in the study protocol ) , and whether the characteristics of the trial itself are associated with risk of bias", "A 6-week , double-blind , parallel group study compared the efficacy and tolerability of paroxetine and fluoxetine in 106 depressed geriatric out patients ( age , ≥65 years ) . Patients with an acute major depressive episode were r and omized to receive either paroxetine ( 20 to 40 mg ; N = 54 ) or fluoxetine ( 20 to 60 mg ; N = 52 ) after a 3− to 7-day washout . Efficacy evaluations at weeks 1 , 3 , and 6 used the 21-item Hamilton Rating Scale for Depression ( HAM-D ) . Cognitive function was assessed by use of the Mini-Mental State Examination ( MMSE ) and the S and oz Clinical Assessment Geriatric Scale ( SCAG ) . Tolerability was assessed by response to a nonleading question concerning adverse events . There were no significant differences between treatments at week 6 on the HAMD total , change from baseline . However , there was a statistically significant difference ( p the MMSE and SCAG showed that , during treatment , patients in the paroxetine group were characterized by greater improvement in cognitive function than were those in the fluoxetine group . This result was statistically significant at week 3 for both scales ( p ) . Adverse events occurred most frequently within the gastrointestinal and nervous systems for both drugs , with no significant differences between treatments", "BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a \" positive \" study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions", "The aim of the present paper was to compare the efficacy and safety of duloxetine with paroxetine in the acute treatment of major depressive disorder ( MDD ) . In a r and omized , double-blind trial of 8 weeks active treatment , patients with non-psychotic MDD were r and omized to duloxetine 60 mg ( n = 238 ) or paroxetine 20 mg ( n = 240 ) once daily . Efficacy was primarily measured on change in the 17-item Hamilton Rating Scale for Depression ( HAMD(17 ) ) using a non-inferiority test with a margin of 2.2 . Secondary efficacy measures included the HAMD(17 ) subscales , Hamilton Rating Scale for Anxiety , Clinical Global Impressions-Severity , Patient Global Impressions-Improvement , Somatic Symptoms Inventory and Visual Analog Scales ( VAS ) for pain . Safety measures included treatment-emergent adverse events ( TEAE ) , vital signs , weight , laboratory analyses and electrocardiograms . Non-inferiority of duloxetine to paroxetine was demonstrated because the upper bound of the confidence interval for mean difference in HAMD(17 ) change ( 0.71 ) was less than the non-inferiority margin . Secondary efficacy end-points did not differ significantly between treatments with the exception of VAS back pain , where the pooled mean was lower in the duloxetine group ( 17.1 ) compared with the paroxetine group ( 20.3 , P = 0.048 ) . No significant differences were observed in the number of early discontinuations and overall TEAE . However , significantly greater proportions of patients in the duloxetine group experienced nausea and palpitations . No clinical ly relevant changes in laboratory values , vital signs , weight or electrocardiograms were observed with either treatment . The present study verifies the utility of duloxetine as an efficacious and safe treatment for both emotional and physical symptoms of MDD in this predominantly Asian patient sample", "The phenylpiperidine derivative paroxetine is a selective serotonin reuptake inhibitor . In a double-blind 6-week trial , paroxetine was compared with amitriptyline in hospitalized patients suffering from major depression ( DSM-III ) . One hundred fifty-three patients were enrolled in the study in seven centers in Austria and Germany . Results showed similar efficacy of both drugs after 6 weeks . The differences between groups in Mont-gomery-Asberg Depression Rating Scale and Clinical Global Impression ratings did not reach statistical significance at any time . Side effects were distributed similarly but with a significantly higher incidence of anticholinergic effects in patients treated with amitriptyline ( p agitation and insomnia were registered more often in the paroxetine group . This study supports the antidepressive efficacy of paroxetine in a sample of severely depressed in patients", "We investigated platelet [14C]serotonin ( 5-HT ) uptake and lysergic acid diethylamide [ N-methyl-3H ] ([3H]LSD)- and phenyl-6′-paroxetine ( [3H]paroxetine ) binding in 30 patients with major depression at baseline and after 6 months of treatment with either paroxetine or sertraline . The study was of a double-blind design . Baseline data was compared with an age- and gender-matched group of healthy volunteers . Baseline Vmax was significantly lower in patients than in controls . Bmax for [3H]paroxetine binding were similar in patients and controls , but patients who suffered their first depression had significantly lower Bmax for [3H]paroxetine binding than patients who had suffered multiple depressions . Twenty-three patients ( 76 % ) ( 13 in the paroxetine group and 10 in the sertraline group ) responded to treatment as judged by a 50 % or more reduction in Montgomery-Asberg Depression Rating Scale ( MADRS ) scores after 6 months of treatment . There were no significant differences between the paroxetine and sertraline treated groups . Both paroxetine and sertraline caused a significant reduction in Vmax and a significant increase in Km . There was a strong correlation between Km and plasma drug concentration in patients who experienced their first depression but not in patients who had suffered multiple episodes . Bmax for [3H]paroxetine binding increased after paroxetine treatment while the opposite occurred after sertraline treatment . There was a significant interaction between the impact of drug and earlier depressions . All patients included in the study had been drug free for at least 2 months . Earlier antidepressant treatment may have long withst and ing effects on the serotonin uptake machinery but it can not be excluded that the sensitivity of the uptake mechanism may become more resistant to change in patients with recurrent depressive episodes", "BACKGROUND Depression is the second most common neuropsychiatric disorder in older Americans , with significant clinical and public health costs . Despite advances in treatment , late-life depression remains a clinical challenge . Although the selective serotonin reuptake inhibitors ( SSRIs ) are the most common pharmacologic intervention for late-life depression , few placebo-controlled trials have assessed the efficacy of SSRIs for this condition . METHOD In this 12-week , multicenter , placebo-controlled , flexible-dose , double-blind , r and omized trial , 319 elderly patients ( mean age = 70 years ) were treated with controlled-release paroxetine ( paroxetine CR ) up to 50 mg/day ( N = 104 ) , immediate-release paroxetine ( paroxetine IR ) up to 40 mg/day ( N = 106 ) , or placebo ( N = 109 ) . Patients met DSM-IV criteria for major depressive disorder and had a total score of 18 or more on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) . The primary efficacy measure was change from baseline to endpoint in HAM-D total score . RESULTS The primary efficacy analysis showed an adjusted difference between change from baseline in HAM-D score for paroxetine CR and placebo of -2.6 ( 95 % confidence interval [ CI ] = -4.47 to -0.73 , p = .007 ) at the week 12 last-observation-carried-forward ( LOCF ) endpoint . The adjusted difference between paroxetine IR and placebo was -2.8 ( 95 % CI = -4.65 to -0.99 , p = .003 ) at week 12 . Paroxetine CR and IR were more effective than placebo , with mean + /- SD endpoint HAM-D total scores of 10.0 + /- 7.41 and 10.0 + /- 7.10 , respectively , for the active treatments compared with 12.6 + /- 7.34 for placebo . Response , defined as a score of 1 or 2 on the Clinical Global Impressions-global improvement scale , was achieved by 72 % of paroxetine CR patients ( LOCF ; p Remission , defined as a HAM-D total score paroxetine CR patients ( LOCF ; p = .009 vs. placebo ) , 44 % of paroxetine IR patients ( p = .01 vs. placebo ) , and 26 % of placebo patients . In a post hoc analysis , mean HAM-D improvement for paroxetine CR and paroxetine IR was greater than for placebo in both chronically depressed patients ( duration > 2 years ) and those with short-term ( or = 2 years ) depression . Dropout rates due to adverse events were 12.5 % for paroxetine CR , 16.0 % for paroxetine IR , and 8.3 % for placebo . CONCLUSION Paroxetine CR and paroxetine IR are effective and well tolerated treatments for major depressive disorder in elderly patients , including those with chronic depression", "A r and omized , double‐blind , parallel‐group , 6‐week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine . After a 1‐week placebo wash‐out , patients suffering from DSM‐III major depression and with a score of 18 or more on the 21‐item Hamilton Rating Scale for Depression ( HRSD ) received either paroxetine or fluoxetine . The patients were assessed for efficacy using the HRSD , Montgomery‐Åsberg Depression Rating Scale and Clinical Global Impression ; for tolerability , adverse events were elicited by the use of a non‐leading question and a side effects checklist . The groups of patients were comparable on entry to the study . One hundred patients were recruited into the study , of whom 78 were evaluable for the efficacy analysis . Paroxetine and fluoxetine showed comparable efficacy at the end of the 6‐week treatment period , but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed . This could suggest an earlier onset of action with paroxetine . Also , associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3 . Patients on paroxetine reported fewer adverse events than those on fluoxetine . The most commonly reported adverse events were nausea and vomiting in both groups", "OBJECTIVE The study examined whether paroxetine inhibits the human norepinephrine transporter in addition to the human serotonin ( 5-HT ) transporter in patients with major depressive disorder . METHOD In an open-label , parallel-group , forced-titration study , 52 out patients with DSM-IV major depressive disorder and a baseline Montgomery Asberg Depression Rating Scale score > or = 20 were r and omly assigned to treatment with paroxetine ( to 60 mg/day ) or desipramine ( to 30 mg/day ) in a 3-to-1 ratio , respectively . Norepinephrine and 5-HT transporter function were assayed by using human transporter transfected cells in the presence of serum collected at baseline and the end of each treatment week . Data from 36 patients were analyzed . RESULTS Paroxetine decreased norepinephrine uptake to 73 % of control ( 27 % inhibition ) at an average serum concentration of 100 ng/ml and 57 % of control ( 43 % inhibition ) at 200 ng/ml . Uptake of 5-HT was decreased to less than 15 % ( greater than 85 % inhibition ) of control at these paroxetine concentrations . Desipramine decreased norepinephrine uptake to near maximal 15 % of control ( 85 % inhibition ) at 100 ng/ml . Uptake of 5-HT was decreased to 82 % of control ( 18 % inhibition ) at 100 ng/ml and 49 % of control ( 51 % inhibition ) at 500 ng/ml . CONCLUSIONS Paroxetine , currently classified as a selective 5-HT reuptake inhibitor , can act as a 5-HT/norepinephrine uptake inhibitor in vivo . The clinical significance of this action on norepinephrine uptake is currently unknown , but this action may contribute to the broad therapeutic efficacy of paroxetine in the treatment of depression , panic disorder , social anxiety disorder , posttraumatic stress disorder , and generalized anxiety disorder", "Brain-derived neurotrophic factor ( BDNF ) is an important member of the neurotrophin family of growth factors , abundant in the brain and periphery . Research ers have reported that serum BDNF levels in drug-free depressed patients are lower than those of healthy controls , and have proposed that these low levels might reflect a failure of neuronal plasticity in depression . In the present study , we investigated the effects of paroxetine , an SSRI , and milnacipran , an SNRI , on serum BDNF levels in depressed patients . Serum levels of BDNF were measured by ELISA before , 4 weeks , and 8 weeks after the start of treatment with antidepressants . Forty-two patients were r and omly administered paroxetine ( 21 cases ) or milnacipran ( 21 cases ) . A negative correlation was found between serum BDNF levels and baseline Ham-D scores . The response and remission rates for each drug were not significantly different . Serum BDNF levels in responders were significantly increased 2.6- and 1.8-fold 8 weeks after treatment with paroxetine or milnacipran , respectively . These results suggest that both drugs improve the depressive state by increasing BDNF levels", "reuptake inhibitors ( SSRIs ) during continuation therapy . This investigation reports the differential effect of 6 months of treatment with sertraline versus paroxetine for symptoms of depression , quality of life , and personality outcomes . Out patients with unipolar major depression ( DSM-III-R ) were r and omly assigned to receive 24 weeks of double-blind treatment with flexible doses of paroxetine ( 20 - 40 mg ) or sertraline ( 50 - 150 mg ) . Assessment s included the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Clinical Global Impression Scale , the Battelle Quality of Life Question naire , and the Structured Clinical Interview for DSM-III-R Personality Disorders screen question naire . One hundred seventy-six patients ( mean age , 43 years ; 64 % female ; baseline MADRS , 30.3 ) were treated with sertraline and 177 patients ( mean age , 42 years ; 71 % female ; MADRS , 30.7 ) with paroxetine . Antidepressant efficacy during continuation therapy was sustained , with only 2 % of patients receiving sertraline and 9 % of patients receiving paroxetine suffering a relapse . Continuation therapy result ed in a substantial conversion of responders during short-term treatment to full remission : remitter rates increased from 52 % to 80 % for sertraline and from 57 % to 74 % for paroxetine . The improvements in quality of life were related to a reduced depression score . SSRI treatment had significant beneficial effects on both categorical and dimensional measures of personality . A logistic regression analysis identified early response ( 25 % reduction in MADRS scores at week 2 ) as the most important predictor of treatment response , whereas high severity , chronicity , and poor baseline quality of life had no effect . Both treatments were well-tolerated , with sertraline having a somewhat lower side effect profile . Sertraline and paroxetine demonstrated comparable efficacy during short-term and continuation therapy . Treatment was associated with significant improvement in quality of life and with reductions in axis II personality psychopathology", "Substance P ( SP ) belongs to the neurokinin ( NK ) family of neuropeptides and exerts its biological effects via interaction with the NK1 receptor . The SP-NK1 receptor system is one of the best-characterized neurotransmitter pathways in both the central and peripheral nervous systems . It has been postulated that this pathway may have important roles in a variety of central ly regulated pathophysiologic conditions , including depression . In animal models , central injection of SP was associated with a series of anxiety-like behaviors , and this response could be abolished by pretreatment with SP ( NK1 ) receptor antagonists ( SPAs ) . On the basis of these and other encouraging pre clinical results , several clinical trials have examined the potential of SPAs in the treatment of depression . In phase 2 trials , therapy with the SPAs aprepitant ( MK-0869 ) and compound A result ed in improvements in depression and anxiety symptoms that were quantitatively comparable with those seen with selective serotonin reuptake inhibitors ( SSRIs ) and significantly greater than those seen with placebo . These positive results have established a proof of concept that the inhibition of the SP-NK1 receptor pathway may be a potentially useful novel treatment option for management of patients with depression . The apparent lack of benefit with SPAs versus placebo in subsequent dose-finding studies with aprepitant and compound A is not surprising , considering the fact that the outcomes with an active control ( SSRI ) in these trials were also similar to those observed with placebo . Future trials with SPAs will focus on the identification of appropriate patients and drug regimens and will also define the role of these agents in the treatment of depression", "A double-blind multicenter r and omized parallel group study comparing paroxetine and maprotiline was carried out in a total of 544 out patients . Included were patients with varying degrees of severity of depressive symptoms who fulfilled modified RDC criteria for either Minor or Major Depression and showed a HAMD-17 score of > or = 13 . No concomitant benzodiazepine treatment was allowed . Duration of treatment was 6 weeks , after an initial wash-out period . Doses were fixed during the first 3 weeks of treatment , patients receiving either 20 mg paroxetine or 100 mg maprotiline daily . An option for dose escalation was provided for insufficient responders after 3 weeks . The weekly assessment s comprised rating of the HAMD-17 , MADRS , BRMS , RDS , HAMA , CAS , and CGI scales and registration of adverse events by non-leading questions . An intention-to-treat and a completer analysis were performed . Response was defined as a HAMD-17 reduction of > or = 50 % or a HAMD-17 score of antidepressant and anxiety-reducing properties for paroxetine and maprotiline . No persistent significant differences between treatment groups were observed on any assessment instrument . There was no difference in the frequency of observed side-effects , but side-effect profiles were markedly different , as maprotiline patients had more anticholinergic and paroxetine patients more SSRI-typical side-effects", "INTRODUCTION : Long-term exposure to antidepressants is required to prevent relapses and recurrences in patients with recurrent major depression . Furthermore , a good pharmacological compliance is the key to successful long-term treatment . Since the early phases of a treatment influence long-term compliance and compliance is adversely affected by poorly tolerated treatments , efficacy and tolerability of paroxetine and amitryptiline over 12 weeks were compared as an introduction to the issue of long-term compliance to these two agents . METHOD : A 12-week , r and omized , double-blind , doubledummy , parallel-group trial which involved 129 patients with recurrent major depression . RESULTS : Both paroxetine and amitriptyline were effective in controlling the symptoms of depression , as shown by the reduction in HAMD total score and CGI severity-of-illness score at endpoint compared to baseline . There was no statistically or clinical ly significant difference between the two treatments in terms of efficacy . However , marked numerical differences were noted in tolerability : the percentage of patients who reported treatment-emergent adverse experiences was greater in the amitriptyline group ( 40.0 % vs 28.1 % ) . This difference was mainly due to anticholinergic adverse events , which were six times more frequent with amitriptyline than with paroxetine . CONCLUSION : When compared with amitriptyline , paroxetine should allow patients with recurrent major depression to receive an equally effective treatment with a relatively lower incidence of adverse experiences", "Unidimensional subscales for assessment of major depression may be more sensitive to antidepressant drug effects than the Hamilton Depression Rating Scale ( HAM-D ) . To further examine this possibility , we analyzed pooled data from eight comparable , well-controlled clinical trials of venlafaxine and compared such subscales and the 17-item HAM-D ( HAM-D(17 ) ) based on effect size and number of patients required for 80 % power . Symptoms of depression were assessed using the HAM-D among intent-to-treat patients ( 2045 ) r and omly assigned to receive venlafaxine ( immediate release , n = 474 ; extended release , n = 377 ) , one of several selective serotonin reuptake inhibitors ( SSRIs ) ( n = 748 ) , or placebo ( n = 446 ) for up to 8 weeks . With SSRIs or venlafaxine vs. placebo , subscales yielded effect sizes ( 0.328 - 0.528 ) 16 to 76 % larger than the HAM-D(17 ) did ( 0.237 and 0.396 , respectively ) , and required 31 to 64 % fewer patients for 80 % power . With venlafaxine vs. SSRIs , the subscales showed no advantage over the HAM-D(17 ) ; all devices yielded comparable , positive effect sizes ( 0.183 - 0.195 ) . Final subscale scores significantly predicted ( all P antidepressant drug effects than the HAM-D(17 ) is , but only in active agent/placebo comparisons . Our data further suggest the subscales can predict the presence of remission . Given these findings , prudent use of these subscales may be appropriate , cost-effective , and informative", "BACKGROUND The aim was to compare the efficacy and tolerability of mirtazapine with those of paroxetine . METHOD 275 out patients with a diagnosis of major depressive episode ( DSM-IV ) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to 6 weeks of treatment with mirtazapine ( 15 - 45 mg/day ) or paroxetine ( 20 - 40 mg/day ) . Efficacy was assessed by the HAM-D-17 , Hamilton Rating Scale for Anxiety ( HAM-A ) , and Clinical Global Impressions scales ( Severity and Improvement ) , and analyses were performed on the intent-to-treat sample ( 127 mirtazapine-treated patients and 123 paroxetine-treated patients ) . RESULTS Mean daily doses were 32.7 mg of mirtazapine and 22.9 mg of paroxetine . Thirty patients in the mirtazapine group and 33 in the paroxetine group dropped out . Both drugs were equally effective in reducing symptoms of depression . At week 1 , the mean HAM-D-17 total score was significantly lower in mirtazapine- than paroxetine-treated patients ( 16.5 vs. 18.8 , p = .0032 ) . Similarly , significantly more mirtazapine-treated patients were HAM-D-17 responders ( > or = 50 % decrease from baseline ) at weeks 1 ( 23.2 % vs. 8.9 % , p = .002 ) and 4 ( 58.3 % vs. 44.5 % , p = .04 ) . Both treatments were equally effective in reducing anxiety . However , the reduction in mean HAM-A total score was significantly greater with mirtazapine than with paroxetine at week 1 ( -5.1 vs. -3.5 , p = .0435 ) . Tolerability of both treatments was good , with more nausea , vomiting , tremor , and sweating in the paroxetine group and more weight increase and influenza-like symptoms in the mirtazapine group . CONCLUSION Mirtazapine and paroxetine were equally effective after 6 weeks of therapy and were both well tolerated . A potentially faster onset of overall therapeutic efficacy of mirtazapine was suggested by significant differences between treatments after 1 week of therapy that were due to slightly larger improvements of several core symptoms of depression as well as distinct prevention of treatment-emergent worsening of anxiety and physical components of depression", "In this study , we tested the influence of the serotonin type 2A , 3A and 3B receptor genes ( HTR2A , HTR3A , HTR3B ) in addition to a polymorphism in the promoter region of the serotonin transporter ( SERTPR ) , and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine . A total of 100 Japanese patients affected by major recurrent depression were enrolled in a r and omized 6-week study . The clinical response was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) , and adverse drug reactions were assessed at each visit . Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers ( p = 0.015–0.042 ) , more significantly to fluvoxamine . The –1438G/G genotype of HTR2A was associated with a good response to SSRIs ( p = 0.010–0.039 ) , especially to fluvoxamine , and significantly with severe nausea in paroxetine-treated patients ( p = 0.013 ) . The 178C/C genotype of the HTR3A was associated with an antidepressant response ( p = 0.022–0.042 ) , and more significantly in paroxetine-treated patients ( p = 0.002–0.042 ) . These effects were independent of one another . We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs . We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy , and the HTR2A polymorphism is also associated with adverse drug reactions . Furthermore , the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI", " The combined serotonin – norepinephrine reuptake inhibitor , venlafaxine XR , has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale ( HAM-D ) . This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR , the selective serotonin reuptake inhibitors ( SSRIs ) fluoxetine or paroxetine , or placebo . Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed . Three treatment groups were compared : venlafaxine XR ( n=560 ) , fluoxetine/paroxetine ( n=298 ) and placebo ( n=496 ) . Mean treatment duration was 8 weeks . Responders were defined as those patients whose HAM-D-21 score decreased by ≥50 % from baseline . Remission was defined as a HAM-D-17 score ≤7 . Sustained remission was defined as maintenance of remission through week 8 or the end of treatment ( if before week 8) and for ≥2 weeks . Between-group rate comparisons in outcome measures were carried out using Fisher 's exact and log-rank tests . Venlafaxine XR produced significantly higher rates of sustained remission in depressed patients compared to fluoxetine/paroxetine or placebo over this 8-week treatment period . As early as week 2 , a significantly greater proportion of patients treated with venlafaxine achieved improved depression scores ( remission and response ) . A significantly greater rate of remission and sustained remission occurred with venlafaxine compared to placebo . Remission was achieved earlier with venlafaxine and lasted throughout the remainder of the study . These results demonstrate that venlafaxine XR is more effective than fluoxetine/paroxetine for sustaining remission of depressive symptoms ", "OBJECTIVES To compare the efficacy of paroxetine and imipramine prospect ively in patients with coexisting depression and dementia . METHODS An 8-week , double-blind , parallel group trial comparing paroxetine 20 - 40 mg/day with imipramine 50 - 100 mg/day in 198 patients aged 60 years or over with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score > or = 20 and a Folstein mini-mental state evaluation score of 17 - 23 points after a 3- to 7-day placebo run-in period . RESULTS Both paroxetine and imipramine reduced the MADRS and the Clinical Global Impression ( CGI ) severity-of-illness and global improvement scores at weeks 2 , 4 , 8 and at endpoint , with no significant differences between treatment groups at any timepoint ( MADRS , p > or = 0.368 ; cgi , p > or = 0.286 ) . There was a statistically significant difference in favour of paroxetine at both the week 4 and week 8 timepoints ( analysis of variance , p Cornell scale for depression in dementia : at endpoint there was no significant difference between treatments ( p = 0.103 ) . Treatment-emergent adverse experiences were reported by 51.5 % ( 51/99 ) of patients treated with paroxetine and 50.5 % ( 50/99 ) of patients treated with imipramine . Anticholinergic adverse experiences ( paroxetine 6.1 % ; imipramine 13.1 % ) and serious non-fatal adverse experiences ( paroxetine 4.0 % ; imipramine 8.1 % ) were reported by more patients in the imipramine group than in the paroxetine group . CONCLUSIONS Paroxetine and imipramine were both effective in the treatment of depression in elderly subjects with co-existing dementia , and no significant differences were detected between the groups . There were trends suggesting that paroxetine was better tolerated than imipramine in terms of anticholinergic adverse experiences and serious non-fatal adverse experiences", "BACKGROUND Sexual dysfunction commonly occurs during antidepressant treatment . However , the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature . The objectives of this study were ( 1 ) to estimate the prevalence of sexual dysfunction among patients taking newer antidepressants ( bupropion immediate release [ IR ] , bupropion sustained release [ SR ] , citalopram , fluoxetine , mirtazapine , nefazodone , paroxetine , sertraline , venlafaxine , and venlafaxine extended release [ XR ] ) and ( 2 ) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction . METHOD This cross-sectional , observational study was conducted in 1101 U.S. primary care clinics . Adult out patients ( 4534 women and 1763 men ) receiving antidepressant monotherapy were enrolled . The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Question naire . RESULTS In the overall population , bupropion IR ( 22 % ) and SR ( 25 % ) and nefazodone ( 28 % ) were associated with the lowest risk for sexual dysfunction , whereas selective serotonin reuptake inhibitor ( SSRI ) antidepressants , mirtazapine , and venlafaxine XR were associated with higher rates ( 36%-43 % ) . In a prospect ively defined sub population unlikely to have predisposing factors for sexual dysfunction , the prevalence of sexual dysfunction ranged from 7 % to 30 % , with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR . Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction . CONCLUSION Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a vali date d rating scale . Overall , SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone . Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians , greater recognition and education are imperative when prescribing antidepressant treatment ", "In view of the fact that controlled prospect i ve studies on the benefits of dose escalation of the selective serotonin re‐uptake inhibitor ( SSRI ) paroxetine are lacking , we conducted a double‐blind , r and omized , parallel‐group multicentre study design ed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria ( RDC ) with inadequate treatment response . The study sample consisted of 544 out‐ patients with different degrees of severity of depression . Patients received either 20 mg paroxetine ( n=271 ) or 100 mg maprotiline ( n=273 ) for the first 3 weeks in a double‐blind manner . Response after 3 weeks was defined using explicit operationalized criteria . Patients with inadequate treatment response ( paroxetine group , n=86 ; maprotiline group , n=88 ) were again r and omized to either continuation of the previous dosage ( paroxetine , n=36 ; maprotiline , n=48 ) or increased doses , i.e. 40 mg paroxetine ( n=50 ) or 150 mg maprotiline ( n=40 ) , respectively . Intention‐to‐treat and completer analyses were performed . Defining response as a reduction in Hamilton Depression Rating Scale ( 17‐item version ) ( HAMD‐17 ) score of at least 50 % from baseline , no significant benefits of dose escalation were found for either paroxetine or maprotiline . Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation . After dose escalation , new adverse events that had not been present during treatment with lower doses rarely occurred . Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients", "BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression", "With regard to the course of basal human hypothalamus-pituitary-adrenal ( HPA ) system activity , there is a lack of data for comparing different classes of antidepressants . Ninety-four patients were included in a study comparing st and ardized treatment with paroxetine ( PAROX ) and amitriptyline ( AMI ) after a drug-free period of at least 6 days . Saliva for measurement of cortisol concentrations was obtained daily at 0800 , 1600 , and 2200 during the 6 days of drug-free washout and 35 days of active treatment . The course of HPA system activity and psychopathology , as assessed by the Hamilton Depression Scale , was compared by means of repeated-measurement analyses of variance ( ANOVA-rm ) . Only AMI responders — not PAROX responders or nonresponders to either antidepressant — had a significant decline in saliva cortisol concentrations . In hypercortisolemically depressed patients , treatment with AMI may be preferable to PAROX in order to lower HPA system activity", "OBJECTIVE To study , whether and how the results from open and double-blind r and omized trials on antidepressants differ . METHODS Seventy-one patients were included in a study comparing open , non-r and omized , st and ardized treatment with paroxetine ( PAROX ) and amitriptyline ( AMI ) after a minimum of six drug-free days ( OPEN ) . A second group of 56 patients received the same treatment under blind-r and omized conditions ( BLIND-R AND OM ) . The course of psychopathology as assessed by the Hamilton Depression Rating Scale was compared using repeated measurements ANOVA-(rm ) . RESULTS While the rate of adverse events was higher in the BLIND-R AND OM compared to the OPEN condition , completer-analyses revealed no differences in psychopathological outcome . CONCLUSIONS With similar clinical outcome BLIND-R AND OM trials of antidepressants may expose depressed patients to an increased risk of adverse events , when compared to OPEN conditions . However , the clinical outcome in study completers did not differ between the BLIND-R AND OM and the OPEN condition . Thus , the psychiatrist 's choice may have impact on adverse events rather than on clinical outcome of antidepressant treatment", "Objective : The primary objective was to evaluate sexual function ( SF ) separately in men and women with major depressive disorder ( MDD ) before and during treatment with bupropion sustained release ( SR ) or paroxetine . The secondary objectives involved a comparative evaluation of the Sex Effects Scale ( Sex FX ) and the Investigator-Rated Sexual Desire and Functioning Scale ( IRSD-F ) , as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time . Method : There were 141 patients ( 68 women and 73 men ) who met DSM-IV criteria for a current major depressive episode . They were r and omly assigned to receive bupropion SR ( 150 to 300 mg daily ) or paroxetine ( 20 to 40 mg daily ) under double-blind trial conditions . Patients were assessed at baseline and at 2 , 4 , 6 , and 8 weeks with the 17-item Hamilton Depression Rating Scale ( HDRS17 ) , Sex FX , and IRSD-F. Results : Prior to treatment , women reported significantly lower SF on both the Sex FX and IRSD-F scales , compared with men . During treatment , there were no significant drug differences on measures of SF over time for women ; however , men who were treated with paroxetine reported a worsening of SF , whereas bupropion SR did not significantly alter SF . Both bupropion SR and paroxetine produced clinical ly and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission . There was a statistically significant correlation between the 2 measures of SF at all visits . There was also a significant inverse relation between depression and SF in women , but not in men , irrespective of drug . Conclusion : According to the Sex FX scale , a significant difference in antidepressant-related sexual dysfunction was detected in men , but not women , during treatment with bupropion SR or paroxetine", "The effects of treatment with serotonin ( 5-HT ) reuptake inhibitors on platelet 5-HT2 receptors , 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors ( SSRI ) , paroxetine , and fluoxetine , for the treatment of major depression . Hamilton Depression Rating Scale ( HAM-D ) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline , after 4 and 8 weeks of treatment , and were compared to 21 healthy controls . Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites , labelled with [3H]paroxetine , or 5-HT2 receptors , labelled with [3H]LSD . However , a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline . A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls . Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively . These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation . Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy , particularly in suicidal depressed patients", "This multi-centre , double-blind study , carried out in France , was design ed to compare the efficacy and tolerability of paroxetine and clomipramine in elderly patients , aged 60 or above , with reactive depression according to Feighner 's criteria . Patients were r and omly allocated to treatment with either paroxetine ( 20 mg o.d . ) , 41 patients , or clomipramine ( increasing from 20 mg o.d . to 20 mg tds ) , 42 patients , for 5 weeks . Placebo tablets were used to maintain blinding . The degree of depression was determined using the Montgomery-Asberg and the Zung self-rating scales , and also assessed on a visual analogue scale . After 5 weeks of treatment both treatment groups showed a similar degree of improvement on all rating scales . There were no significant differences between the groups . Adverse events occurred in 26 and 28 patients in the paroxetine and clomipramine groups , respectively . In the paroxetine group , many of the events were typical of the gastrointestinal side-effects associated with 5-HT uptake inhibitor therapy . Patients receiving clomipramine experienced events of the type commonly reported with tricyclic antidepressants . There were no significant differences between the groups for either total number of events or for number of patients with specific events . Clinical and laboratory monitoring showed that both drugs were well tolerated", "Objective : This study was performed to compare the clinical efficacy , side effects , and safety of paroxetine and maprotiline , the latter being the most frequently prescribed antidepressant in Switzerl and . Method : Seventy-one patients ( in and out patients ) with major depression were r and omly allocated to treatment with paroxetine ( 20 to 40 mg daily ) or with maprotiline ( 50 to 150 mg daily ) . Efficacy was measured by means of the Hamilton Psychiatric Rating Scale for Depression , the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impression , and the Hopkins Symptom Checklist . Results : The 2 components showed a similar efficacy . The adverse effect profile was comparable in the 2 treatment groups , although the findings showed a nonsignificant trend pointing in the direction of lower side effects with paroxetine . Conclusion : In the moderate dose regimens tested , the 2 components seemed to be of similar efficacy , with comparable profiles of side effects and safety", "Paroxetine is a novel phenylpiperidine antide-pressant agent that acts as a potent and selective inhibitor of serotonin reuptake . We report results of a 6-week , r and omized , double-blind , multicenter study comparing paroxetine and fluoxetine in the treatment of major depression . One hundred seventy-eight in patients , who met DSM-III-R criteria for a major depressive episode and had a Montgomery Asberg Depression Rating Scale ( MADRS ) score of 24 or more , were included in the study . Their ages ranged from 18 to 65 years . Subjects were r and omized to receive either paroxetine or fluoxetine for 6 weeks . A 20-mg fixed dose , given once daily in the morning , was used for both drugs . After baseline , regular assessment s were made at the end of weeks 1,2,3,4 , and 6 . Efficacy measures included the MADRS , the Clinical Global Impression severity of illness scale , the Hamilton Rating Scale for Anxiety , the Hospital Anxiety and Depression scale , and the Visual Analogue Scale for anxiety . Safety and tolerability were assessed by adverse event reports , clinical examinations , vital signs , and laboratory data . A marked antidepressant response and good tolerability were seen with both drugs . These results further support the usefulness of paroxetine in the treatment of depressive illness", "BACKGROUND 60%-90 % of patients with a primary diagnosis of depression also experience symptoms of anxiety , and such patients have a poorer prognosis than those with uncomplicated depression . The serotonin selective reuptake inhibitors have demonstrated efficacy in the treatment of both depression and certain anxiety states . Furthermore , in a meta analysis of the paroxetine clinical trial data base of 2963 patients in whom depression predominated , there was a concomitant reduction in the Hamilton Rating Scale for Depression anxiety factor . The purpose of the present study was to prospect ively compare the efficacy of paroxetine and clomipramine in patients specifically selected for coexisting depression and anxiety . METHOD This was a 12-week , double-blind , parallel-group trial comparing paroxetine 20 - 40 mg/day with clomipramine 75 - 150 mg/day in 1002 patients with a Montgomery-Asberg Depression Rating Scale ( MADRS ) score > or = 20 and a Clinical Anxiety Score ( CAS ) > or = 11 after a 3 - 7 day placebo run-in period . RESULTS Both paroxetine and clomipramine reduced the MADRS and CAS ratings at 2 , 6 , and 12 weeks and at endpoint , with no significant differences between treatment groups at any time point . CGI severity of illness and global improvement ratings were also similar throughout the trial ; however , there was a statistically significant difference in the CGI efficacy index at 6 weeks and at endpoint , favoring paroxetine ( p = .015 and p = .015 , respectively ) . Paroxetine result ed in fewer treatment-emergent adverse experiences and related withdrawals than clomipramine ( p = .025 and p = .008 , respectively ) . The number of serious adverse experiences was not significantly different in the paroxetine group compared with the clomipramine group ( 14 [ 2.8 % ] vs. 27 [ 5.4 % ] ) , but did approach statistical significance ( p = .056 ) . Anticholinergic-emergent adverse experiences were reported twice as frequently by patients in the clomipramine group as in the paroxetine group ( 36.1 % vs. 18.6 % ) . CONCLUSION There was no evidence of any significant difference in efficacy between paroxetine and clomipramine in patients with coexisting depression and anxiety . However , paroxetine was better tolerated as shown by total treatment-emergent adverse experiences , anticholinergic adverse experiences , and withdrawals due to adverse experiences", "Agomelatine ( S 20098 ) has a unique and new pharmacological profile . It is a melatoninergic agonist and selective antagonist of 5-HT2C receptors , and has been shown to be active in several animal models of depression . The aim of this study was to determine the active dose of agomelatine in the treatment of major depressive disorder ( DSM-IV criteria ) . The methodology used was a conventional double-blind design comparing three different doses of agomelatine ( 1 , 5 and 25 mg once a day ) with placebo over an 8-week treatment period . Paroxetine was used as the study validator . Seven hundred and eleven patients with a baseline mean score of 27.4 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) were included . On the pivotal analysis , the mean final HAM-D total score ( Full Analysis Set LOCF ) demonstrated agomelatine 25 mg to be statistically more effective than placebo . This was confirmed by other analyses and criteria ( responders , remission , sub population of severely depressed patients , Montgomery – Åsberg Depression Rating Scale , Clinical Global Impression-Severity of Illness ) . Agomelatine 25 mg alleviated the anxiety associated with depression , as measured on Hamilton Anxiety Scale . Paroxetine was found to be effective on pivotal analysis and most of the secondary criteria used to vali date the study methodology and population . Agomelatine , whatever the dose , showed good acceptability with a side-effects profile close to that of placebo . In conclusion , this study demonstrates that agomelatine is efficient in the treatment of major depressive disorder and that 25 mg is the target dose", "Abstract Objective : This study was performed to compare the efficacy and safety of tianeptine and paroxetine in the treatment of major depression . Anxiolytic drug use was systematic ally reported to provide an indirect evaluation of the anxiolytic activity of both treatments . Zopiclone use was assessed to provide an indirect evaluation of the possible hypnotic activity of both treatments . Design and Setting : This was a 3-month controlled , r and omised , double-blind clinical trial which involved 82 centres in France . Patients x : 277 out patients who met DSM-IV criteria for major depression . Interventions : Patients were treated with either tianeptine ( 12.5 mg three times daily ) or paroxetine ( 20 mg once daily plus two placebo capsules ) . The drug dosages could be doubled after 3 weeks if required by the patient ’s medical state . Main Outcome Measures and Results : There was a significant decrease in the Montgomery-Åsberg Depression Rating Scale score in both groups ( from 28.9 at baseline to 11 at endpoint in the tianeptine group , and from 29.6 to 11.6 in the paroxetine group ) after 3 months of treatment . No significant difference was evident between the groups . Secondary criteria confirmed the antidepressant efficacy of both medications , with no difference between tianeptine and paroxetine ( Hamilton Depression Rating Scale global score at endpoint , Clinical Global Impression final scores , number of responders , delay-to-response , rate of dosage doubling at day 21 ) . The anxiolytic and hypnotic consumption rates decreased in both groups , with no significant difference between the groups . There was no significant difference in clinical safety parameters . Conclusion : Tianeptine appears to be as effective and as safe as paroxetine for the ambulatory treatment of major depression", "BACKGROUND Fluvoxamine and paroxetine , both serotonin selective reuptake inhibitors ( SSRIs ) , were compared at two centers in a 7-week double-blind study in out patients with major depression , diagnosed by DSM-III-R criteria . METHOD Sixty patients were r and omly assigned to receive dosage titrated upward to between 50 - 150 mg/day of fluvoxamine ( N = 30 ) or 20 - 50 mg/day of paroxetine ( N = 30 ) . The mean + /- SD daily dose administered at the last assessment was 102 + /- 44 mg/day for fluvoxamine and 36 + /- 13 mg/day for paroxetine . Sixteen ( 53 % ) fluvoxamine-treated patients and 10 ( 33 % ) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug . Sample size was calculated to provide at least 85 % power at 5 % level of significance to detect at least a 1.00-point difference in mean severity of adverse events , assuming a st and ard deviation of 1.0 . RESULTS Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 + /- 7.3 ( p Hamilton Rating Scale for Depression ( HAM-D ) . Adverse events were mostly mild to moderate in severity . The most common events were headache ( N = 17 , 57 % ) , nausea ( N = 14 , 47 % ) , sweating ( N = 10 , 33 % ) , somnolence ( N = 9 , 30 % ) , diarrhea ( N = 9 , 30 % ) , dry mouth ( N = 8 , 27 % ) , dizziness ( N = 8 , 27 % ) , and , among males , impotence ( N = 3 , 21 % ) and ejaculatory abnormality ( N = 3 , 21 % ) in the paroxetine group , and headache ( N = 12 , 40 % ) , somnolence ( N = 12 , 40 % ) , nausea ( N = 11 , 37 % ) , dry mouth ( N = 11 , 37 % ) , insomnia ( N = 9 , 30 % ) , asthenia ( N = 7 , 23 % ) , and dyspepsia ( N = 7 , 23 % ) in the fluvoxamine group . The only statistically significant difference between treatment groups was for sweating ( 33 % paroxetine vs. 10 % fluvoxamine , p = .028 ) . CONCLUSION Observed differences in some side effects , although not statistically significant , indicate that when a patient has difficulty tolerating one SSRI , the clinician may choose to change to a different agent within the same class", "In a double‐blind clinical study , antidepressant plasma levels , parameters of platelet serotonin ( 5‐HT ) transport ( Km , Vmax and basal platelet 5‐HT content ) and therapeutic response were measured in depressive patients treated with either paroxetine ( 30 mg/day ) or amitriptyline ( 150 mg/day ) for 6 weeks . No correlation could be found between paroxetine plasma levels and therapeutic outcome after 2 , 4 and 6 weeks of treatment . In contrast to the amitriptyline group , a marked increase in Km from baseline to week 2 was determined in paroxetine‐treated patients , with Km increase being correlated with paroxetine plasma levels at week 2 . However , no significant relationship could be found between 5‐HT transport parameters and any of the outcome measures in either treatment group", "A total of 151 out patients with endogenous or mixed endogenous and reactive depression were included in a 6‐week double‐blind study , with extension for up to 1 year , in psychiatric practice . The results showed trends in efficacy variables and a statistically significant difference in a benefit‐risk ratio in favour of paroxetine ( Seroxat ® , Paxil ® ) compared with imipramine . Efficacy was largely maintained in both groups during long‐term treatment . The frequency and severity of side effects in paroxetine patients declined markedly from short‐term to long‐term treatment , whereas changes in imipramine patients were less pronounced . Significantly more imipramine patients gained weight during long‐term treatment . In conclusion , paroxetine is an effective and well tolerated antidepressant , well suited for out patients in psychiatric practice", "Two hundred hospitalized patients with DSM-III diagnosis of moderate to severe major depressive episode were r and omized to receive mirtazapine or trazodone for 6 weeks in a double-blind trial . The dosages were 24–72 mg/day for mirtazapine and 150–450 mg/day for trazodone . The improvement on all depression rating scales used was generally greater for mirtazapine , wish statistically significant differences over trazodone in the Hamilton Psychiatric Rating Scale for Depression total score and two subscores ( the Bech melancholia factor and retardation factor ) , the Brief Psychiatric Rating Scale total score , the General Psychiatric Impression Global Assessment Scale , the Beck score and responder rates . Mirtazapine was well tolerated , while the trazodone-treated patients experienced somnolence more frequently , particularly during the first 2 weeks of treatment . Furthermore , postural symptoms were a clinical problem in > ' 6 % of the trazodone-treated patients . In this trial , mirtazapine showed significant clinical advantages over trazodone in terms of overall efficacy and tolerability", "Paroxetine is a selective serotonin uptake inhibitor , which is being investigated as an antidepressant . In this double‐blind , six‐week study 120 out patients with DSM‐I11 major depression were r and omly assigned to treatment with paroxetine , imipramine , or placebo . Results showed a statistically significant superiority of paroxetineover placebo on almost all outcome measures . Paroxetine was significantly superior to imipramine on the HAMD total score and was generally better tolerated than imipramine . The results support paroxetine 's effectiveness in the treatment of major depression and suggest that further studies with this compound are warranted", "Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor ( SSRI ) . Ninety-one hospitalised patients with a major depression ( DSM-III ) aged 65 and over from six Austrian and one German center were entered into the study , which compared the efficacy and tolerability of paroxetine versus amitriptyline . After 6 weeks both groups showed similarly good therapeutic results . In the paroxetine group , 64.3 % of the patients had a 50 % or more reduction of the HAMD total score compared to 58.1 % in the amitriptyline group . Side effects were distributed similarly in both groups . Patients in the paroxetine group showed a higher incidence of anxiety and agitation ; anticholinergic side effects were registered more often in the amitriptyline group", "BACKGROUND Depression is a serious and widespread emotional disorder among the elderly . This study compared the efficacy and safety of bupropion sustained release ( SR ) with the selective serotonin reuptake inhibitor paroxetine in the treatment of major depression in elderly out patients . METHOD Elderly ( > or = 60 years ) out patients with major depressive disorder ( DSM-IV criteria ) were evaluated in this 6-week multicenter , r and omized , double-blind study comparing bupropion SR , 100 - 300 mg/day , and paroxetine , 10 - 40 mg/day . Efficacy was assessed by changes in scores on the Hamilton Rating Scales for Depression ( HAM-D ) and Anxiety ( HAM-A ) and the Clinical Global Impressions-Severity of Illness and -Improvement scales . Safety was assessed by monitoring adverse events , vital signs , and body weight . RESULTS A total of 100 patients ranging in age from 60 to 88 years were r and omly assigned to treatment with bupropion SR ( N = 48 ) or paroxetine ( N = 52 ) . Measurements of efficacy were similar between the 2 treatment groups , with both groups showing improved scores on all depression rating scales . Headache , insomnia , dry mouth , agitation , dizziness , and nausea occurred in > 10 % of patients in both groups ; somnolence , diarrhea , constipation , and anorexia occurred in > 10 % of patients in the paroxetine group . No statistically significant differences between groups in vital signs or weight were found . CONCLUSION Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly . Because of its favorable side effect profile , bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly", "BACKGROUND Some studies have suggested that selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients . The objective of this study was to compare the 6-week outcome of treatment with nortriptyline and paroxetine in older patients with a major depressive episode . METHOD A double-blind r and omized comparison of nortriptyline and paroxetine was conducted in 80 elderly ( mean + /- SD age = 75.0 + /- 7.4 years ) psychiatric in patients and out patients who presented with a major depressive episode . Dropout and response rates were compared in patients who began or completed treatment . Rates of response of in patients and patients with melancholic depression were also compared . RESULTS Over 6 weeks , there were no significant differences in dropout rates due to side effects ( nortriptyline , 14 % vs. paroxetine , 19 % ) or for any reason ( 27 % vs. 33 % ) . Similarly , there were no significant differences between the rates of favorable response to nortriptyline or paroxetine ( intent-to-treat analysis , 57 % vs. 44 % ; completer analysis , 78 % vs. 66 % ) . Analyses restricted to in patients or to patients with melancholic depression yielded similar results . CONCLUSION Nortriptyline and paroxetine appear to have similar efficacy and tolerability in the acute ( 6-week ) treatment of older depressed patients , including hospitalized patients and those with melancholic features", "ABSTRACT — Paroxetine is a new antidepressant drug . It is a potent and selective 5‐HT re‐uptake inhibitor with only weak anticholinergic properties and less effect on the cardiovascular system than the classical tricyclics . In this double‐blind multicenter study the antidepressant effect of paroxetine was compared with mianserin in 70 patients with unipolar or bipolar depression . Each drug was administered for 6 weeks after a 1 week run‐in period at a daily dosage of 30 mg for paroxetine or 60 mg for mianserin . The 21‐item Hamilton Depression Rating Scale ( HAM‐D ) and the physician 's global assessment were used to assess efficacy . Both treatment groups showed statistically significant improvement of the HAM‐D at Weeks 1 ( base‐line values : paroxetine mean 28.5 ; mianserin mean 30.8 ) through to Week 6 ( paroxetine mean 11.5 ; mianserin mean 17.8 ) ( P The endpoint differences between treatments however were not statistically different ( P= 0.11 ) . The Cleary and Guy factor analysis showed a significant difference ( P for cognitive disturbance and at Weeks 4 and 6 for retardation in favour of paroxetine compared with mianserin . Both drugs were well tolerated with nausea and headache in four patients and somnolence in six patients being reported as the most common side‐effect for paroxetine and mianserin respectively", "The objective of this study was to compare the safety and efficacy of paroxetine with imipramine and placebo in depressed out patients . Following a 4- to 14-day placebo washout , patients were r and omized into treatment groups and received study compound for up to 42 days . At Day 42 , paroxetine was significantly more effective than placebo ( p less than .05 ) in several observer- and patient-rated scales : the Retardation and Anxiety/Somatization factors of the Hamilton Rating Scale for Depression ( HAM-D ) , the Montgomery-Asberg Depression Rating Scale ( MADRS ) , the Raskin Depression Scale , the Covi Anxiety Scale , the Clinical Global Impressions ( CGI ) Improvement Scale , the Symptom Checklist-56 ( SCL-56 ) Total , and the Patient 's Global Evaluation ( PGE ) . There were no significant differences between paroxetine and imipramine . Significantly more imipramine ( 75 % ) than paroxetine ( 35 % ) or placebo ( 23 % ) patients reported anticholinergic side effects , including blurred vision ( 5 % , 0 % , and 0 % , respectively ) , constipation ( 35 % , 8 % , and 15 % , respectively ) , and dry mouth ( 63 % , 25 % , and 15 % , respectively ) . The data from this study indicated that paroxetine is a safe , well-tolerated , effective treatment for major depressive disorder", "OBJECTIVE In this study the authors evaluated the efficacy and the tolerability of sertraline and paroxetine in the treatment of delusional depression . METHOD Under double-blind conditions , 46 hospitalized patients who met the DSM-III-R criteria for major depression with psychotic features were treated with sertraline or paroxetine for 6 weeks . RESULTS The response rates were 75 % and 46 % for sertraline and paroxetine , respectively . The dropout rate was substantial ( 41 % ) in the paroxetine group and was attributable to side effects . CONCLUSIONS Selective serotonin reuptake inhibitors administered alone are useful in the treatment of delusional depression", "BACKGROUND Sleep effects of antidepressants are important clinical ly and for elucidating mechanism of action : selective serotonin reuptake inhibitors disturb sleep and 5-HT(2 ) receptor-blocking compounds may enhance sleep quality . AIMS To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression . METHOD Forty patients with depression were r and omised to take paroxetine 20 - 40 mg/day or nefazodone 400 - 600 mg/day for 8 weeks . Objective and subjective quality of sleep and depression measures were assessed throughout . RESULTS Nefazodone significantly increased objective sleep efficiency and total sleep time , and improved subjective sleep on days 3 and 10 . Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8 . Paroxetine but not nefazodone produced marked suppression of rapid eye movement ( REM ) sleep . CONCLUSIONS Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression . These effects are seen within the first 2 weeks of treatment and diminish thereafter", "This article describes a 6-week study evaluating body sway during double-blind therapy with nortriptyline versus paroxetine in geriatric patients . Body sway was measured with patients ' eyes open , then closed , using a stable force platform at 4 timepoints : before starting antidepressant medication , and after 1 , 2 , and 6 weeks of treatment . Measures such as the length ( L ) of path of the center of pressure ( COP ) and the area included within the COP path were selected for quantitative assessment of stability . A repeated measures analysis of variance ( ANOVA ) model with planned comparisons was used to examine the pair-wise difference at baseline and Weeks 1 , 2 , and 6 of treatment . No significant difference was found in body sway parameters over the 6 weeks of study for patients treated with either nortriptyline or paroxetine", "The primary objective of this multicentre , r and omized , double-blind study carried out in France was to compare the efficacy and safety of a 6-week treatment with paroxetine ( 20 mg/day ) or mianserine ( 30 mg/day ) in geriatric hospitalized or ambulatory patients ( > or = 60 years ) treated for a major depressive disorder ( according to DSM III-R ) . A secondary objective was to discriminate those items predicting the response to an agent according to its serotoninergic or noradrenergic pharmacologic profile . The tool used for this latter purpose was the Aubin-Jouvent-Rating-Scale ( AJRS ) which was design ed to assess the deficit of serotonin : this is a scale with 10 items , some of them regrouped into a \" general \" factor ( irritability , sudden mood change , impatience , aggressivity ) or a \" depression \" factor ( pain , anxiety , suicidal ideas ) with additional items related to sleep disorders , abnormalities in eating behavior and inability to tolerate isolation . In the perspective of this assessment , paroxetine was chosen due to its potential to inhibit serotonin re-uptake , as compared to mianserin which blocks presynaptic alpha-adrenergic receptors with negligible action on serotonin . This was a multicenter study carried out in France in 50 hospital or private practice psychiatrists . The assessment criteria included the MADRS , the AJRS , the COVI 's anxiety scale , the Folstein 's Mini-mental state ( MMS ) as well as a global assessment by the investigator at the end of the study . Safety was measured with a nondirective question naire , routine laboratory tests as well as a global assessment by the investigator . The primary efficacy criteria was the change in the MADRS global score . Statistical analysis included chi-square or Fisher 's test as well as Student 's and Wilcoxon tests for comparability at baseline , and analysis of variance for the changes in scores as during the study . A total of 116 patients was r and omised ( paroxetine : 54 ; mianserine : 62 ) , of whom 96 completed the study ( paroxetine : 43 ; mianserine : 53 ) . With the exception of MADRS moderately higher in the paroxetine group , both groups were comparable at baseline . After 6 weeks of treatment , a marked improvement was recorded in both groups for all criteria except MMS ; there was a consistent tendency favouring paroxetine which reached statistical significance for the COVI ' scale ( p = 0.001 ) . For a given criterion , the difference paroxetine versus mianserine appeared related to the score at baseline ; it was also more marked in those patients with a AJRS baseline score > or = 20 with a difference for MADRS reduction of marginal significance in favor of paroxetine ( p = 0.061 ) . As regards safety , at least one adverse event was reported in 31.5 % of the patients receiving paroxetine versus 41.9 % in those receiving mianserin ( NS ) ; premature withdrawal related to an adverse event was reported in 11.1 % of the patients in the paroxetine group versus 12.9 % in the mianserin group . No abnormality of clinical significance was reported in either group concerning laboratory tests . In conclusion , this study confirmed the therapeutic value and good safety of paroxetine as an antidepressant in geriatric population s , especially when exist a concomitant anxiety or symptoms likely to reflect a deficit of serotonine ( irritability , emotional lability , restlessness , aggressivity ) and to predict a good response to an agent such as this one", "ABSTRACT – Paroxetine is a new antidepressant drug with potent serotonin ( 5HT ) uptake inhibitory properties . In this double‐blind comparative study , the antidepressant effect of paroxetine and amitriptyline has been compared in 44 patients with depressive illnesses of an endogenous nature . Each drug was given for 6 weeks . The 17‐item Hamilton Depression Scale was used to measure the antidepressant effect . Reported events were assessed applying a 22‐item check list . Non‐parametric statistical analyses were applied in the evaluation of treatment outcome for the 30 patients who completed the study . The results showed no significant differences in overall antidepressant efficacy between paroxetine and amitriptyline and that paroxetine displayed significantly fewer instances of dry mouth and orthostatic dizziness than amitriptyline . No obvious relationship was demonstrated between the plasma levels of the drugs and their clinical effects", " Patients and methods Male and female patients diagnosed as having a major episode of depression according to DSM-111 criteria , and who had aminimum score of 18 on the 21-item Hamilton Depression Rating Scale ( HAMD ) , were eligible for entry into the study . Pregnant or lactating women , patients with severe co-existing diseases , known alcohol abusers , and those known to be intolerant of tricyclic antidepressants were excluded", "Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature , but currently none of them is generally accepted . For the treatment of these conditions , only few recommendations based on empirical data are available . We conducted a r and omized double-blind multicentre study in depressed out patients comparing paroxetine and maprotiline in both patients with minor ( n = 245 ) and major depression ( n = 298 ) . For the diagnosis , Research Diagnostic Criteria were used in a modified version . Two response criteria were applied : a reduction of 50 % or more in total HAMD-17 scores from baseline ( criterion 1 ) , and a reduction of the HAMD-17 total score to 9 points or less ( criterion 2 ) . A completer and an endpoint analysis was performed . For patients with minor depression , remarkably high response rates were found for paroxetine ( criterion 1 : 90.9 % completer , 82.1 % endpoint ; criterion 2 : 89.1 % completer , 82.4 % endpoint ) while the respective rates for maprotiline tended to be lower ( criterion 1 : 80.4 % completer , 71.4 % endpoint ; criterion 2 : 84.9 % completer ; 76.1 % endpoint ) . Response rates in patients with major depression were for paroxetine : criterion 1 : 74.3 % completer , 62.8 % endpoint ; criterion 2 : 76.4 % completer , 65.2 % endpoint ; and for maprotiline : criterion 1:82.4 % completer , 68.5 % endpoint ; criterion 2 : 80.6 % completer ; 66.0 % endpoint , which resembles rates reported from previous antidepressant trials . Both drugs were generally well tolerated . Though no placebo control was carried out , our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine , but also with maprotiline at a favourable risk/benefit ratio", "We aim ed to compare the antidepressant and anxiolytic effects , tolerability and effects on quality of life of mirtazapine and citalopram in a r and omized , double-blind , multicentre , 8-week study . Patients with a Major Depressive Episode ( DSM-IV ) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were r and omized to 8 weeks treatment with either mirtazapine ( n = 137 , 15 - 60 mg/day ) or citalopram ( n = 133 , 20 - 60 mg/day ) . Efficacy was evaluated by the MADRS , Hamilton Anxiety Scale ( HAM-A ) , Clinical Global Impression scales ( CGI ) , the Leeds Sleep Evaluation Question naire ( LSEQ ) and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method . Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit . The magnitude of reduction from baseline in group mean MADRS scores was large in both groups , reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group . Both treatments also result ed in a substantial improvement in anxiety symptoms , sleep disturbances and quality of life , and high percentage of responders . However , at day 14 , statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS , HAM-A and CGI-Severity of illness and Quality of life scores . A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinical ly relevant superiority between two proven antidepressants . Mirtazapine treatment was also related to faster improvement of sleep , quality of sleep and improved alertness following awakening , as shown by statistically significant differences on the self-rating LSEQ at various time points . There were no differences between two treatment groups on self-rating QLSEQ . Both drugs were well tolerated , with a low number of patients in either group prematurely terminating the study due to adverse events ( mirtazapine : 3.6 % , citalopram , 3.0 % ) . Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group . There were no clinical ly relevant changes in laboratory parameters and vital sign variables with either treatment , except for clinical ly relevant increase in body weight , occurring more frequently in mirtazapine patients . In this study , mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety , and well tolerated . However , mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS , HAM-A and CGI Severity of illness and Quality of life scales . This finding , consistently present at all major efficacy variables , suggests potentially faster onset of efficacy of mirtazapine over citalopram", "Patients and dosage Forty patients who fulfilled the DSM-III criteria of major depressive illness , the severity of which corresponded to at least 18 points on the 21-item Hamilton Depression Rating Scale ( HAMD ) , were entered into the study . The majority suffered from drug-refractory depression : 26 ( 6 5 % ) patients had been treated with antidepressant medication earlier in the current phase , without a satisfactory improvement in any of these patients . After a minimum washout period of three days , the patients were r and omized into two groups of 20 patients each . One group received paroxetine , 30 mg daily as a single dose and the second amitriptyline , 1SOmg daily . Both drugs were given for a period of six weeks", "BACKGROUND Clinical studies of endogenous concentrations of dehydroepi and rosterone ( DHEA ) and its sulfated conjugate DHEA-S in depression are limited . This study was design ed to evaluate the influence of successful pharmacological treatment of late-life depression on concentrations of DHEA , DHEA-S and cortisol . METHODS We determined endogenous concentrations of DHEA , DHEA-S and cortisol in elderly control subjects ( n = 16 ) and in elderly depressed patients who remitted ( n = 44 ) or failed to remit ( n = 16 ) with pharmacological treatment . Depressed patients were treated for 12 weeks with either nortriptyline or paroxetine . RESULTS In remitters , DHEA and DHEA-S concentrations were lower at week 12 than at week 0 ( p = .002 and p = .0001 , respectively ) . In the nonremitters and control subjects , neither DHEA nor DHEA-S concentrations changed . Decreases in hormone concentrations were associated with improvement in mood and functioning in depressed patients . Although cortisol concentrations decreased in remitters and nonremitters , the change was not significant . CONCLUSIONS Our data suggest that the decrease in DHEA and DHEA-S in remitters is related to remission of depression rather than to a direct drug effect on steroids , as nonremitters had no change in hormone concentrations", "Paroxetine is a novel antidepressant that selectively inhibits neuronal reuptake of serotonin . Results are reported from a 6-week , double-blind trial of paroxetine , imipramine , and placebo in 120 out patients with DSM-III major depression . Paroxetine was significantly superior to placebo on almost all measures . This included the main outcome variable , the Hamilton Rating Scale for Depression ( HAM-D ) , and its factor scores , anxiety-somatization , cognitive disturbance , psychomotor retardation , and sleep disturbance . There were no significant differences between paroxetine and imipramine on the same scales . Imipramine-treated patients were significantly more likely than those taking placebo to report one or more adverse effects , which were predominantly anticholinergic in nature . There was no significant difference in the number of paroxetine and placebo patients who reported one or more adverse effects . The results of this and similar studies indicate that paroxetine is an effective treatment in major depression and has a favorable side effect profile", "CONTEXT Major depressive disorder causes significant morbidity and mortality . Current therapies fail to fully treat both emotional and physical symptoms of major depressive disorder . OBJECTIVE To evaluate duloxetine , a dual reuptake inhibitor of serotonin and norepinephrine , on improvement of emotional and painful physical symptoms . DESIGN R and omized , double-blind , evaluation of duloxetine at 40 mg/d ( 20 mg twice daily ) and 80 mg/d ( 40 mg twice daily ) versus placebo and paroxetine 20 mg/d in depressed out patients . MAIN OUTCOME MEASURES The primary efficacy measure was the 17-item Hamilton Depression Rating Scale . Visual Analog Scales for pain , Clinical Global Impression of Severity , Patient 's Global Impression of Improvement , and Quality of Life in Depression Scale were also used . Safety was evaluated by assessing discontinuation rates , adverse event rates , vital signs , and laboratory tests . RESULTS Duloxetine 80 mg/d was superior to placebo on mean 17-item Hamilton Depression Rating Scale total change by 3.62 points ( 95 % CI 1.38 , 5.86 ; P = 0.002 ) . Duloxetine at 40 mg/d was also significantly superior to placebo by 2.43 points ( 95 % CI 0.19 , 4.66 ; P = 0.034 ) , while paroxetine was not ( 1.51 points ; 95 % CI -0.55 , 3.56 ; P = 0.150 ) . Duloxetine 80 mg/d was superior to placebo for most other measures , including overall pain severity , and was superior to paroxetine on 17-item Hamilton Depression Rating Scale improvement ( by 2.39 points ; 95 % CI 0.14 , 4.65 ; P = 0.037 ) and estimated probability of remission ( 57 % for duloxetine 80 mg/d , 34 % for paroxetine ; P = 0.022 ) . The only adverse event reported significantly more frequently for duloxetine 80 mg/d than for paroxetine was insomnia ( 19.8 % for duloxetine 80 mg/d , 8.0 % for paroxetine ; P = 0.031 ) . Hypertension incidence was not affected by any treatment . CONCLUSION Duloxetine therapy was efficacious for emotional and physical symptoms of depression , with a selective serotonin reuptake inhibitor-like profile of side effects", "This double-blind study compared initial combination therapy against monotherapy using two antidepressant drugs with complementary mechanisms of action on the serotonin ( 5-HT ) and norepinephrine ( NE ) systems . Sixty one adult patients with a DSM-IV diagnosis of unipolar depression were r and omized to receive mirtazapine ( 30 mg/day ) , paroxetine ( 20 mg/day ) , or the combination of both drugs for 6 weeks . Response at week 4 was defined as a 30 % reduction in the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and at week 6 as a 50 % reduction in the MADRS . Remission was defined as a reduction in the MADRS score to 10 points or less . After 4 weeks , non-responders in the monotherapy groups had their medication dose increased by 50 % . After 6 weeks , non-responders on monotherapy had the second trial drug added to their current regimen . Non-responders on combination therapy had the dosage of both drugs increased by 50 % . There was a significantly greater decrease in MADRS scores in the combination group compared to the monotherapy groups at days 28 , 35 and 42 , with a 10 point difference separating the combination from the monotherapies at day 42 . Remission rates at week 6 were 19 % on mirtazapine , 26 % on paroxetine , and 43 % on the combination . Fifteen patients in the mirtazapine arm and 10 in the paroxetine arm who did not respond had the other drug added to their current regimen , and 5 on the combination had an increase in dose of both drugs secondary to non-response . Of these 30 patients , approximately 50 % went on to achieve remission in the subsequent 2 weeks . These results indicate that the combined use of two antidepressants was well tolerated and produced a greater improvement than monotherapy", "Results from a single-center , 6-week , double-blind , r and omized prospect i ve study of paroxetine , a selective serotonin reuptake inhibitor ; imipramine ; and placebo are reported . One hundred twenty out patients with a moderate-to-severe DSM-III diagnosis of major depression were r and omly assigned to one of the three treatments following a 4- to 10-day single-blind placebo washout period . Significant differences favoring paroxetine over placebo were present at endpoint on most major efficacy measures . Paroxetine was also well tolerated ; 5 ( 15 % ) paroxetine and 5 ( 14 % ) placebo patients dropped out of the study due to adverse effects . Imipramine , however , was comparatively poorly tolerated . Forty-five percent of imipramine-treated patients ( N = 17 ) dropped out of the study due to adverse effects . None of the efficacy measures showed a significant difference between imipramine and placebo . This finding was probably due to the high number of imipramine patients who discontinued before they could improve . These results support the efficacy of paroxetine in the treatment of major depression and underline its favorable side effect profile compared with tricyclic antidepressants", "BACKGROUND The effects of extended selective serotonin reuptake inhibitor ( SSRI ) treatment on weight are not well characterized . Also unknown is whether different agents have differential effects . To examine these questions , we assessed weight changes in patients r and omly assigned to long-term treatment with fluoxetine , sertraline , or paroxetine . METHOD Patients ( N = 284 ) with major depressive disorder ( DSM-IV ) were r and omly assigned to double-blind treatment with fluoxetine ( N = 92 ) , sertraline , ( N = 96 ) , or paroxetine ( N = 96 ) for a total of 26 to 32 weeks . The mean percent change in weight was compared for each group , as was the number of patients who had > or = 7 % weight increase from baseline . RESULTS Patients ( fluoxetine , N = 44 ; sertraline , N = 48 ; paroxetine , N = 47 ) who completed the trial were included in these analyses . Paroxetine-treated patients experienced a significant weight increase , fluoxetine-treated patients had a modest but nonsignificant weight decrease , and patients treated with sertraline had a modest but nonsignificant weight increase . The number of patients whose weight increased > 7 % from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients . CONCLUSION Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used", "OBJECTIVE Although adverse events are a key factor in compliance , their evolution during treatment with antidepressants is poorly documented . Therefore , the time course of adverse events during 6 months of antidepressant treatment was investigated . METHOD 85 psychiatric out patients with a DSM-IV diagnosis of major depressive disorder ( with the exclusion of other DSM-IV Axis I disorders ) were enrolled between September 2002 and March 2003 in a multicenter , r and omized , double-blind trial with selective serotonin reup-take inhibitors ( fluoxetine [ N = 42 ] and paroxetine [ N = 43 ] ) . At each visit , the presence and severity of treatment-emergent adverse events were assessed systematic ally using the UKU Side Effect Rating Scale ( UKU ) . General linear mixed modeling was used to investigate the predictors of the time course of adverse events . RESULTS Overall , the number of at least moderately severe adverse events decreased with time . More severely depressed patients reported overall more ( at least moderately severe ) adverse events than less severely depressed patients ( p = .0002 ) , but the decrease in reported adverse events was comparable over time . Men ( N = 30 ) and women ( N = 55 ) reported initially the same number of at least moderately severe adverse events , but the habituation was more rapid in men ( p habituation was more rapid ( p = .014 ) . The habituation of adverse events was also more rapid in recurrent than in first-episode patients but only in men ( p = .0025 ) . CONCLUSION The time course of adverse events varies with the severity of depression , sex , completer or dropout status , and recurrent versus first-episode depression", "The efficacy of amisulpride in depressive disorders has been demonstrated in dysthymia and in double depression . Limited data are available in major depression . A r and omized , double-blind , parallel group , multicentre study was set up to compare the efficacy and tolerability of amisulpride ( 50 mg o.d . ) and paroxetine ( 20 mg o.d . ) for 8 weeks in 272 patients with major depression ( DSM-IV and baseline Hamilton Depression Rating Scale ( HAMD ) score ≥18 ) . The study was design ed as a non-inferiority trial based on the proportion of responders ( ≥50 % decrease in HAMD total score ) at end-point , with a maximal allowable difference of 15 % ; secondary end-points included HAMD total and cluster scores , Montgomery and Asberg Depression Rating Scale score and responders rates and Clinical Global Impression improvement . The tolerability evaluation was based on incidence of adverse events and routine laboratory tests . The results did not disclose statistically significant differences between treatments , although the hypothesis of an efficacy difference between the two treatments within the set limit at day 56 could not be accepted . The issue of non-inferiority trials is discussed", "The effects of an abrupt interruption of agomelatine , a new melatonergic/serotonergic antidepressant , were explored in a double-blind , placebo-controlled study . Paroxetine was used as active control . After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day , sustained remitted depressed patients were r and omized for 2 weeks , under double-blind conditions , to placebo or to their initial antidepressant treatment . Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms ( DESS ) checklist . One hundred and ninety-two sustained remitted patients were r and omized to the 2-week discontinuation period . Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine . Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms , during the first week , compared to those who continued with paroxetine ( respective mean number of emergent symptoms : 7.3±7.1 and 3.5±4.1 , P to paroxetine , abrupt cessation of agomelatine is not associated with discontinuation symptoms ", "Objective : The development of the Antidepressant Compliance Question naire ( ADCQ ) , assessing patients ’ attitudes and beliefs on depression and antidepressants", "A six-week , double-blind , r and omised study was used to compare the efficacy , tolerability , safety and effect on cognitive function of paroxetine with that of lofepramine in the treatment of 138 patients with major depression in general practice . Efficacy was assessed using the Montgomery and Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) scale . Effect on cognitive function was assessed using the paired associate learning test and the serial \" E ' cancellation test . The results showed that the antidepressant efficacy of paroxetine was comparable to that of lofepramine in the treatment of depressed patients . Similar improvements in mean total MADRS scores were observed in both treatment groups , but a significantly greater improvement was seen in the CGI with paroxetine at weeks 2 and 4 . The effect of treatment on cognitive function did not differ significantly across the two treatment groups , nor did the number of adverse events reported nor the overall tolerability", "There is some empirical evidence that selective serotonin reuptake inhibitors reduce suicidal ideas faster than other antidepressants . These findings are well in line with the theory of a serotonergic hypofunction in suicidal patients . To test this hypothesis the data of a 6-week double-blind control-group study comparing paroxetine versus amitriptyline were analyzed with respect to suicidality . The global antidepressive efficacy was comparable under dosages of 30 mg paroxetine or 150 mg amitriptyline per day . A differentiated analysis failed to confirm the hypothesis of a faster reduction of suicidal cognitions by paroxetine", "Abstract : Depressed patients may exhibit reduced heart rate variability ( HRV ) , and antidepressants which block norepinephrine uptake may also lower HRV . This study compared paroxetine ( PAR ) and venlafaxine XR ( VEN-XR ) on HRV . Out patients were r and omly assigned to double-blind treatment with PAR up to 40 mg or VEN-XR up to 225 mg daily . HRV measures of parasympathetic control consisted of change in R-R interval during forced 10-second breaths and respiratory sinus arrhythmia ( RSA ) during paced breathing . Ex vivo estimates of serotonin and norepinephrine transporter occupancy were obtained before and after treatment , as were measures of depression , anxiety , and resilience . Plasma drug concentrations were measured at end point . Forty-nine patients entered treatment ; 44 of whom were evaluable ( n = 22 per group ) . Significant within-group reductions were noted in R-R interval variation and in RSA after VEN-XR only . Between-group analyses showed significant group-by-time interaction , with greater reduction in R-R interval variation and in RSA for VEN-XR compared with PAR . Improvement in resiliency correlated significantly with norepinephrine transporter occupancy for VEN-XR . Further comparisons of selective serotonin reuptake inhibitor and serotonin and norepinephrine reuptake inhibitor drugs on HRV are warranted", "Objective To assess the potential economic impact of new and more expensive antidepressants on the overall cost of treatment using cost-effectiveness analysis . Method For this analysis , a computerized decision tree of clinical practice was developed to model the 12-month treatment of moderate to severe depression in Canada . To complete the model , data were obtained from physician panels , the Ontario Ministry of Health , and clinical comparative trials of paroxetine , a selective serotonin reuptake inhibitor , and Imipramine , a tricyclic antidepressant . Results The overall cost of treatment when paroxetine 30 mg per day was used first-line was found to be lower than when generic imipramine was used as the initial therapy ( $ 1697 versus $ 1793 ) . The higher drug cost of paroxetine ( $ 1.69 per day ) versus imipramine ( $ 0.05 per day ) was offset by a higher rate of treatment failures with the tricyclic necessitating an alternate therapy , additional physician visits and /or hospitalization . Sensitivity analysis of key variables determined that drug price and relapse rates after discontinuation were relatively insensitive predictors of the overall cost of care . More important was the continuation rate while on different therapies . Conclusion Paroxetine demonstrated a cost-benefit relative to Imipramine when the continuation rate was ≥ 47 % . Clinical trials of paroxetine have reported continuation rates of 41 % to 65 % , suggesting that paroxetine is a cost-effective alternative to Imipramine in the 1-year management of patients with moderate to severe depression", "21 depressed patients of the Basle University Psychiatric Outpatient Clinic were treated in a double-blind study with paroxetine and amitriptyline . 11 of these patients did not continue the trial until the end of the 7th week . There was a significant difference in the number of dropouts between the two groups : 80 % of the amitriptyline group did not continue until the end , while in the paroxetine group we found only 30 % dropouts . The patients of both groups showed a gradual decrease of the median total scores on the Hamilton and the Montgomery and Asberg Depression Rating Scales . Although the number of patients who stayed in the trial for at least 4 weeks ( 8 with paroxetine , 6 with amitriptyline ) is quite small , we see from the results of the clinical global impression that the members of the paroxetine group improved most of all in the somatic symptoms , while considering their moods we found no differences between the groups . Patients of both groups complained about side effects , most of all about dry mouth and tiredness . From the high rate of dropouts under amitriptyline we found that the side effects under this drug were more severe and therefore led to the dropouts", "Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as \" mortality , \" \" other objective , \" \" or subjective , \" and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes" ]	41186f12-06ff-11f0-808a-c43d1ab1c353
Background / Objectives : Vitamin D may modify the risk of type 2 diabetes mellitus . The aim of this review was to examine the association between vitamin D status and incident type 2 diabetes , and the effect of vitamin D supplementation on glycemic outcomes . Methods : We performed a systematic review of English- language studies using MEDLINE through February 2011 . Longitudinal cohort studies reporting associations between vitamin D status and incident type 2 diabetes , and r and omized controlled trials ( RCTs ) of vitamin D supplementation , were included . Study characteristics and results were extracted , and study quality was assessed . Results : A total of 8 observational cohort studies and 11 RCTs were included . In meta-analyses of observational studies , vitamin D intake > 500 international units (IU)/day decreased the risk of type 2 diabetes by 13 % compared with vitamin D intake vitamin D status ( > 25 ng/ml ) had a 43 % lower risk of developing type 2 diabetes ( 95 % confidence interval 24 , 57 % ) compared with those in the lowest group ( participants with normal glucose tolerance at baseline and in three small underpowered ( n=32–62 ) trials of patients with established type 2 diabetes , there was no effect of vitamin D supplementation on glycemic outcomes . In two trials among patients with baseline glucose intolerance , vitamin D supplementation improved insulin resistance . Conclusions : Vitamin D may play a role in type 2 diabetes ; however , to better define the role of vitamin D in the development and progression of type 2 diabetes , high- quality observational studies and RCTs that measure blood 25-hydroxyvitamin D concentration and clinical ly relevant glycemic outcomes are needed	[ "Low serum 25-hydroxyvitamin D ( 25(OH)D ) has been shown to correlate with increased risk of type 2 diabetes . Small , observational studies suggest an action for vitamin D in improving insulin sensitivity and /or insulin secretion . The objective of the present study was to investigate the effect of improved vitamin D status on insulin resistance ( IR ) , utilising r and omised , controlled , double-blind intervention administering 100 microg ( 4000 IU ) vitamin D(3 ) ( n 42 ) or placebo ( n 39 ) daily for 6 months to South Asian women , aged 23 - 68 years , living in Auckl and , New Zeal and . Subjects were insulin resistant - homeostasis model assessment 1 (HOMA1)>1.93 and had serum 25(OH)D concentration vitamin D supplementation > 25 microg ( 1000 IU)/d . The HOMA2 computer model was used to calculate outcomes . Median ( 25th , 75th percentiles ) serum 25(OH)D(3 ) increased significantly from 21 ( 11 , 40 ) to 75 ( 55 , 84 ) nmol/l with supplementation . Significant improvements were seen in insulin sensitivity and IR ( P = 0.003 and 0.02 , respectively ) , and fasting insulin decreased ( P = 0.02 ) with supplementation compared with placebo . There was no change in C-peptide with supplementation . IR was most improved when endpoint serum 25(OH)D reached > or = 80 nmol/l . Secondary outcome variables ( lipid profile and high sensitivity C-reactive protein ) were not affected by supplementation . In conclusion , improving vitamin D status in insulin resistant women result ed in improved IR and sensitivity , but no change in insulin secretion . Optimal vitamin D concentrations for reducing IR were shown to be 80 - 119 nmol/l , providing further evidence for an increase in the recommended adequate levels . Registered Trial No. ACTRN12607000642482", "OBJECTIVE —Accumulating epidemiological evidence suggests that hypovitaminosis D may be associated with type 2 diabetes and related metabolic risks . However , prospect i ve data using the biomarker serum 25-hydroxyvitamin D [ 25(OH)D ] are limited and therefore examined in the present study . RESEARCH DESIGN AND METHODS —A total of 524 r and omly selected nondiabetic men and women , aged 40–69 years at baseline , with measurements for serum 25(OH)D and IGF-1 in the population -based Ely Study , had glycemic status ( oral glucose tolerance ) , lipids , insulin , anthropometry , and blood pressure measured and metabolic syndrome risk ( metabolic syndrome z score ) derived at baseline and at 10 years of follow-up . RESULTS —Age-adjusted baseline mean serum 25(OH)D was greater in men ( 64.5 nmol/l [ 95 % CI 61.2–67.9 ] ) than women ( 57.2 nmol/l [ 54.4,60.0 ] ) and varied with season ( highest late summer ) . Baseline 25(OH)D was associated inversely with 10-year risk of hyperglycemia ( fasting glucose : β = −0.0023 , P = 0.019 ; 2-h glucose : β = −0.0097 , P = 0.006 ) , insulin resistance ( fasting insulin β = −0.1467 , P = 0.010 ; homeostasis model assessment of insulin resistance [ HOMA-IR ] : β = −0.0059 , P = 0.005 ) , and metabolic syndrome z score ( β = −0.0016 , P = 0.048 ) after adjustment for age , sex , smoking , BMI , season , and baseline value of each metabolic outcome variable . Associations with 2-h glucose , insulin , and HOMA-IR remained significant after further adjustment for IGF-1 , parathyroid hormone , calcium , physical activity , and social class . CONCLUSIONS —This prospect i ve study reports inverse associations between baseline serum 25(OH)D and future glycemia and insulin resistance . These associations are potentially important in underst and ing the etiology of abnormal glucose metabolism and warrant investigation in larger , specifically design ed prospect i ve studies and r and omized controlled trials of supplementation", "BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170", "OBJECTIVE The purpose of this study was to prospect ively examine the association between vitamin D and calcium intake and risk of type 2 diabetes . RESEARCH DESIGN AND METHODS In the Nurses ' Health Study , we followed 83,779 women who had no history of diabetes , cardiovascular disease , or cancer at baseline for the development of type 2 diabetes . Vitamin D and calcium intake from diet and supplements was assessed every 2 - 4 years . During 20 years of follow-up , we documented 4,843 incident cases of type 2 diabetes . RESULTS After adjusting for multiple potential confounders , there was no association between total vitamin D intake and type 2 diabetes . However , the relative risk ( RR ) of type 2 diabetes was 0.87 ( 95 % CI 0.75 - 1.00 ; P for trend = 0.04 ) comparing the highest with the lowest category of vitamin D intake from supplements . The multivariate RRs of type 2 diabetes were 0.79 ( 0.70 - 0.90 ; P for trend calcium intake from all sources and 0.82 ( 0.72 - 0.92 ; P for trend 1,200 mg calcium and > 800 IU vitamin D was associated with a 33 % lower risk of type 2 diabetes with RR of 0.67 ( 0.49 - 0.90 ) compared with an intake of vitamin D and calcium intake in reducing the risk of type 2 diabetes", "CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867", "Background — Individuals with vascular or valvular calcification are at increased risk for coronary events , but the relationship between calcium consumption and cardiovascular events is uncertain . We evaluated the risk of coronary and cerebrovascular events in the Women ’s Health Initiative r and omized trial of calcium plus vitamin D supplementation . Methods and Results — We r and omized 36 282 postmenopausal women 50 to 79 years of age at 40 clinical sites to calcium carbonate 500 mg with vitamin D 200 IU twice daily or to placebo . Cardiovascular disease was a prespecified secondary efficacy outcome . During 7 years of follow-up , myocardial infa rct ion or coronary heart disease death was confirmed for 499 women assigned to calcium/vitamin D and 475 women assigned to placebo ( hazard ratio , 1.04 ; 95 % confidence interval , 0.92 to 1.18 ) . Stroke was confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to placebo ( hazard ratio , 0.95 ; 95 % confidence interval , 0.82 to 1.10 ) . In subgroup analyses , women with higher total calcium intake ( diet plus supplements ) at baseline were not at higher risk for coronary events ( P=0.91 for interaction ) or stroke ( P=0.14 for interaction ) if assigned to active calcium/vitamin D. Conclusions — Calcium/vitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in generally healthy postmenopausal women over a 7-year use period", "Aims /hypothesisCalcium and vitamin D have been implicated in the development of type 2 diabetes , but epidemiological evidence is limited . We examined prospect ively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort . Methods Participants were 59,796 middle-aged and older men and women , who participated in the Japan Public Health Center-based Prospect i ve Study and had no history of type 2 diabetes or other serious diseases . Dietary intake of calcium and vitamin D were estimated using a vali date d food frequency question naire . Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes . Results During a 5 year follow-up , 1,114 cases of type 2 diabetes were documented . Overall , calcium intake was not associated with a significantly lower risk of type 2 diabetes ; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 ( 95 % CI 0.71–1.22 ) in men and 0.76 ( 95 % CI 0.56–1.03 ) in women . However , among participants with a higher vitamin D intake , calcium intake was inversely associated with diabetes risk ; the odds ratio for the highest vs lowest intake categories was 0.62 ( 95 % CI 0.41–0.94 ) in men and 0.59 ( 95 % CI 0.38–0.91 ) in women . Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only . Conclusions /interpretationCalcium and vitamin D may not be independently associated with type 2 diabetes risk . Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation", "Background Studies have suggested that vitamin D may be important for both insulin sensitivity and insulin secretion , and that supplementation with vitamin D may subsequently prevent development of type 2 diabetes . Aim of the study The objective of the current study was to test the hypothesis that supplementation with vitamin D would improve glycaemic control in subjects with type 2 diabetes . Methods Thirty-six subjects with type 2 diabetes , treated with metformin and bed-time insulin , were r and omised to supplementation with cholecalciferol ( 40,000 IU per week ) versus placebo for 6 months . Thirty-two subjects participated throughout the entirety of the study . Fasting blood sample s were drawn before and at the end of the 6 month study without the previous bed-time insulin injection . The insulin and metformin doses were not changed throughout the study . Results After 6 months , the fasting glucose , insulin , C-peptide , fructosamine , and HbA1c levels were not significantly different from baseline values . In addition , changes in these parameters ( values at 6 months minus values at baseline ) did not differ between the vitamin D and the placebo group . Conclusions We were not able to demonstrate that vitamin D supplementation had a significant effect on glucose metabolism in subjects with type 2 diabetes but without vitamin D deficiency . Further studies are needed in larger groups of subjects with type 2 diabetes or impaired glucose tolerance , who also exhibit low serum 25-hydroxyvitamin D levels", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "AIM To determine the short-term effect of vitamin D(3 ) supplementation on insulin sensitivity in apparently healthy , middle-aged , central ly obese men . SUBJECTS AND METHODS A double-blind r and omized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3 ) ( 120,000 IU each ; supplemented group ) fortnightly or placebo ( control group ) . Hepatic fasting insulin sensitivity [ homeostasis model assessment ( HOMA ) , quantitative insulin-sensitivity check index , HOMA-2 ] , postpr and ial insulin sensitivity [ oral glucose insulin sensitivity ( OGIS ) ] , insulin secretion ( HOMA%B , HOMA2-%B ) , lipid profile and blood pressure were measured at baseline and at 6 weeks ' follow-up . RESULTS Seventy-one of the recruited subjects completed the study ( 35 in supplemented group , 36 in control group ) . There was an increase in OGIS with supplementation by per protocol analysis ( P = 0.038 ; intention-to-treat analysis P = 0.055 ) . The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant ( mean difference 41.1 + /- 15.5 ; P = 0.01 ) . No changes in secondary outcome measures ( insulin secretion , basal indices of insulin sensitivity , blood pressure or lipid profile ) were found with supplementation . CONCLUSION The trial indicates that vitamin D(3 ) supplementation improves postpr and ial insulin sensitivity ( OGIS ) in apparently healthy men likely to have insulin resistance ( central ly obese but non-diabetic )", "AIMS To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels . METHODS Double-blind , parallel group , placebo-controlled r and omized trial . A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter , when levels of circulating 25-hydroxyvitamin D were likely to be lowest . Patients were enrolled if their baseline 25-hydroxyvitamin D level was Endothelial function and blood pressure were measured and fasting blood sample s were taken at baseline and 8 weeks after administration of vitamin D. RESULTS Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation ( FMD ) of the brachial artery by 2.3 % . The improvement in FMD remained significant after adjusting for changes in blood pressure . Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo ; this did not correlate with change in FMD . CONCLUSIONS Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotl and . A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency", "Vitamin D recently has been proposed to play an important role in a broad range of organ functions , including cardiovascular ( CV ) health ; however , the CV evidence -base is limited . We prospect ively analyzed a large electronic medical records data base to determine the prevalence of vitamin D deficiency and the relation of vitamin D levels to prevalent and incident CV risk factors and diseases , including mortality . The data base contained 41,504 patient records with at least one measured vitamin D level . The prevalence of vitamin D deficiency ( ≤30 ng/ml ) was 63.6 % , with only minor differences by gender or age . Vitamin D deficiency was associated with highly significant ( p prevalence of diabetes , hypertension , hyperlipidemia , and peripheral vascular disease . Also , those without risk factors but with severe deficiency had an increased likelihood of developing diabetes , hypertension , and hyperlipidemia . The vitamin D levels were also highly associated with coronary artery disease , myocardial infa rct ion , heart failure , and stroke ( all p with incident death , heart failure , coronary artery disease/myocardial infa rct ion ( all p stroke ( p = 0.003 ) , and their composite ( p vitamin D deficiency in the general healthcare population and an association between vitamin D levels and prevalent and incident CV risk factors and outcomes . These observations lend strong support to the hypothesis that vitamin D might play a primary role in CV risk factors and disease . Given the ease of vitamin D measurement and replacement , prospect i ve studies of vitamin D supplementation to prevent and treat CV disease are urgently needed", "BACKGROUND AND AIM Cross-sectional studies indicate vitamin D to be of importance for glucose tolerance , blood pressure and serum lipids , but whether supplementation with vitamin D would improve cardio-vascular risk factors is not known . DESIGN AND SETTING The study was a 1 year , double blind placebo-controlled intervention trial performed at the University Hospital of North Norway from November 2005 to October 2007 . Subjects . A total of 438 overweight or obese subjects , 21 - 70 years old , were included and 330 completed the study . INTERVENTIONS The subjects were r and omized to vitamin D ( cholecalciferol , vitamin D(3 ) ) 40 000 IU per week ( DD group ) , vitamin D 20 000 IU per week ( DP group ) , or placebo ( PP group ) . All subjects were given 500 mg calcium daily . MAIN OUTCOME MEASURES Fasting serum lipids and blood pressure were measured and an oral glucose tolerance test performed at start and end of the study . RESULTS At baseline the mean serum 25(OH)D levels were 58 nmol L(-1 ) ( all subjects ) and increased to 140 and 101 nmol L(-1 ) in the DD and DP groups , respectively . No significant differences were found between the three groups regarding change in measures of glucose metabolism or serum lipids . In the DP group , there was a slight but significant increase in systolic blood pressure compared with the placebo group . CONCLUSIONS Our results do not support a positive effect of vitamin D on glucose tolerance , blood pressure or serum lipids . Further studies in subjects with low serum 25(OH)D levels combined with impaired glucose tolerance , hypertension or dyslipidaemia are needed" ]	41186f4e-06ff-11f0-808a-c43d1ab1c353
The aim of the present systematic review was to synthesize data from r and omized controlled trials investigating the effects of olive oil on markers of inflammation or endothelial function . Literature search in electronic data bases Cochrane Trial Register , EMBASE , and MEDLINE was performed . Thirty studies enrolling 3106 participants fulfilled the selection criteria . Pooled effects of different interventions were assessed as mean difference using a r and om effects model . Olive oil interventions ( with daily consumption ranging approximately between 1 mg and 50 mg ) result ed in a significantly more pronounced decrease in C-reactive protein ( mean difference : -0.64 mg/L , ( 95 % confidence interval ( CI ) -0.96 to -0.31 ) , p interleukin-6 ( mean difference : -0.29 ( 95 % CI -0.7 to -0.02 ) , p Values of flow-mediated dilatation ( given as absolute percentage ) were significantly more increased in individuals subjected to olive oil interventions ( mean difference : 0.76 % ( 95 % CI 0.27 to 1.24 ) , p olive oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function , thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet . However , due to the heterogeneous study design s ( e.g. , olive oil given as a supplement or as part of dietary pattern , variations in control diets ) , a conservative interpretation of the results is necessary	[ "Background A high consumption of omega‐3 long‐chain polyunsaturated fatty acids , and particularly docosahexaenoic acid ( DHA ) , has been suggested to reduce the risk of cardiovascular disease ( CVD ) . However , while DHA supplementation may have benefits for secondary prevention , few studies have investigated the role of DHA in the primary prevention of CVD . Here , we tested the hypothesis that DHA supplementation improves endothelial function and risk factors for CVD . Methods and Results Healthy volunteers ( n=328 ) , aged 18 to 37 years , were r and omly assigned to 1.6 g DHA/day ( from a microalgae source ) together with 2.4 g/day carrier oil ( index group ) or to 4.0 g/day olive oil ( control ) ( both given in eight 500‐mg capsules/day for 16 weeks ) . Flow‐mediated endothelium‐dependent vasodilation ( FMD ) of the brachial artery ( primary outcome ) was measured before and after the intervention ( n=268 ) using high‐resolution vascular ultrasound . FMD was the same in both groups at r and omization ( mean , SD ; 0.27 , 0.1 mm ) , but postintervention was higher in the control group ( 0.29 , 0.1 mm ) compared with the DHA‐supplemented group ( 0.26 , 0.1 mm ; mean difference −0.03 mm ; 95 % CI −0.005 to −0.06 mm ; P=0.02 ) . Of other outcomes , only triglyceride ( mean difference −28 % , 95 % CI −40 % to −15 % ; P concentrations were significant lower in DHA‐supplemented individuals compared with controls . Conclusions DHA supplementation did not improve endothelial function in healthy , young adults . Nevertheless , lower triglyceride concentrations with DHA supplementation was consistent with previous reports and could have benefits for the prevention of CVD . Clinical Trial Registration Information URL : http://www.controlled-trials.com/ Unique identifier : IS RCT N no : 19987575", "BACKGROUND AND AIMS Virgin olive oil ( VOO ) and nuts are basic components of the Mediterranean diet , a heart-healthy dietary pattern . Nuts have well known cholesterol lowering effects , while evidence is unclear for VOO . We design ed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40 % of the fat in the background diet with VOO , walnuts or almonds . METHODS AND RESULTS After a 4 week run-in period with a healthy diet , eligible c and i date s were r and omized into three diet sequences in a crossover design , with a common background diet enriched with VOO , walnuts or almonds , lasting 4 weeks each . Outcomes were changes of serum lipids and oxidation and inflammation markers , measured by st and ard methods . Plasma fatty acids were determined by gas chromatography to assess compliance . In 18 participants completing the study ( 9 women , mean age 56 y , BMI 25.7 kg/m(2 ) ) , LDL-cholesterol was reduced from baseline by 7.3 % , 10.8 % and 13.4 % after the VOO , walnut and almond diets , respectively ( P = 0.001 , Friedman test ) . Total cholesterol and LDL/HDL ratios decreased in parallel . LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets . No changes of other lipid fractions , oxidation analytes or inflammatory biomarkers were observed . Plasma fatty acid changes after each diet sequence supported good compliance . CONCLUSION The results confirm the cholesterol lowering properties of nut-enriched diets . They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content , which clearly deserves further study", "The intake of ( n-3 ) long-chain PUFA is associated with a decreased risk of fatal myocardial infa rct ion . Whether this effect is attributable to the effects of docosahexaenoic acid [ 22:6(n-3 ) ( DHA ) ] on vascular function , particularly at intakes placebo controlled trial of 0.7 g DHA/d as a purified algal derived triacylglycerol ( 1.5 g/d ) vs. placebo ( 1.5 g olive oil/d ) on vascular function and biochemical indices of endothelial dysfunction in 38 healthy men and women , aged 40 - 65 y. Each treatment phase lasted 3 mo , separated by a 4 mo washout period . Supplementation increased the proportion of DHA in erythrocytes lipids by 58 % , compared with placebo . Arterial compliance and endothelium independent and dependent responses , plasma concentrations of C-reactive protein , soluble thrombomodulin , E-selectin , von Willebr and factor antigen , and urinary microalbumin and isoprostane excretion were unaffected by treatment . Diastolic blood pressure decreased by 3.3 mm Hg ( 95 % CI -6.1 to -0.6 ; P = 0.01 ) . Heart rate tended to be 2.1 beats/min lower after DHA treatment than after the placebo period ( P = 0.15 ) . The results indicate that a moderate increase in the daily intake of DHA to approximately 0.7 g DHA lowers diastolic BP but does not influence indices of endothelial function or arterial stiffness in the short term", "A mixture of trans-10 , cis-12 ( t10,c12 ) and cis-9 , trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA mixture ) reduced atherosclerosis in animals , thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest . We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture , an oil rich in the naturally occurring c9,t11 CLA ( CLA milk ) , respectively , or olive oil for 16 wk in a double-blind , r and omized , parallel intervention study . We sample d blood and urine before and after the intervention . The ratios of total cholesterol : HDL cholesterol and concentrations of C-reactive protein , fibrinogen , and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk . Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil . Both CLA supplements increased lipid peroxidation , a marker of in vivo oxidative stress measured as urinary free 8-iso-prostagl and in F(2alpha ) . However , the CLA mixture increased lipid peroxidation more than the CLA milk did . The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments , nor were any of the other variables measured . In conclusion , oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease , whereas the c9,t11 CLA isomer is more neutral , except for a small but significant increase in lipid peroxidation compared with olive oil", "BACKGROUND AND PURPOSE Activation of endothelial cells and platelets is an important mediator of atherothrombosis . Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma . We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebr and factor ( vWF ) , primarily reflecting activation of endothelial cells , and increased concentrations of soluble P-selectin and platelet-derived microvesicles ( PDM ) , primarily reflecting activation of platelets , compared with healthy controls . We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism . METHODS We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 r and omly selected community controls stratified by age , sex , and postal code . Using established criteria , we classified cases of stroke by etiological subtype in a blinded fashion . The prevalence of vascular risk factors and blood concentrations of E-selectin , P-selectin , vWF antigen , and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls . RESULTS Mean blood concentrations of soluble E-selectin , P-selectin , and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls . At 3 to 6 months after stroke , the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls , and PDM concentrations remained elevated . There was a strong , grade d , and independent ( of age , sex , and vascular risk factors ) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke , particularly ischemic stroke caused by large-artery atherothrombosis . There was also a significant , grade d , and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis . CONCLUSIONS We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis . Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke", "BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension", "Background Adherence to the Mediterranean diet ( MD ) is associated with reduced morbidity and mortality due to cardiovascular disease . However , how the MD exerts its effects is not fully known . Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED ( Prevención con Dieta Mediterránea ) study . Methods A total of 164 participants at high risk for cardiovascular disease were r and omized into three diet groups : MD supplemented with 50mL/d of extra virgin olive oil ( MD+EVOO ) or 30 g/d of nuts ( MD+Nuts ) and a low-fat diet . Changes in classical cardiovascular risk factors , inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention . Results Compared to participants in the low-fat diet group , those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic ( 6mmHg ) and diastolic ( 3mmHg ) blood pressure ( P = 0.02 ; both ) , as well as a reduction of 10 % and 8 % in LDL-cholesterol ( P = 0.04 ) , respectively . Patients in the MD+Nuts group showed a significant reduction of 34 % in CD40 expression on monocyte surface compared to low-fat diet patients ( P = 0.03 ) . In addition , inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45 % and 35 % and 95 % and 90 % in the MD+EVOO and MD+Nuts groups , respectively ( P sICAM and P-selectin were also reduced by 50 % and 27 % , respectively in the MD+EVOO group ( P = 0.04 ) and P-selectin by 19 % in MD+Nuts group ( P = 0.04 ) compared to the low-fat diet group . Conclusions Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain , at least in part , the protective role of MD against ischemic heart disease . Trial Registration www.controlled-trials.com IS RCT", "BACKGROUND Adherence to the Mediterranean diet ( Med-Diet ) is associated with a reduced risk of cardiovascular disease ( CVD ) . However , the molecular mechanisms involved are not fully understood . OBJECTIVE The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD . DESIGN In a controlled study , we r and omly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups : Med-Diet with supplemental virgin olive oil ( VOO ) , Med-Diet with supplemental nuts , and low-fat diet . Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo . RESULTS One hundred six participants ( 43 % women ; average age : 68 y ) completed the study . At 3 mo , monocyte expression of CD49d , an adhesion molecule crucial for leukocyte homing , and of CD40 , a proinflammatory lig and , decreased ( P Serum interleukin-6 and soluble intercellular adhesion molecule-1 , inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces , decreased ( P Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO ( P interleukin-6 , soluble vascular cellular adhesion molecule-1 , and soluble intercellular adhesion molecule-1 increased ( P Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD . The results support the recommendation of the Med-Diet as a useful tool against CVD", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Objective —To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke , including biomarkers of hemostasis , inflammation , and endothelial activation as well as chemokines and adipocytokines . Methods and Results —The Prospect i ve Epidemiological Study on Myocardial Infa rct ion ( PRIME ) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years . In a nested case – control study , 95 ischemic stroke cases were matched with 190 controls . After multivariable adjustment for traditional risk factors , fibrinogen ( odds ratio [ OR ] , 1.53 ; 95 % confidence interval [ CI ] , 1.03–2.28 ) , E-selectin ( OR , 1.76 ; 95 % CI , 1.06–2.93 ) , interferon-&ggr;-inducible-protein-10 ( OR , 1.72 ; 95 % CI , 1.06–2.78 ) , resistin ( OR , 2.86 ; 95 % CI , 1.30–6.27 ) , and total adiponectin ( OR , 1.82 ; 95 % CI , 1.04–3.19 ) were significantly associated with ischemic stroke . Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 ( 95 % CI , 0.612–0.745 ) to 0.785 and 0.788 , respectively , and yielded a categorical net reclassification improvement of 29.9 % ( P=0.001 ) and 28.4 % ( P=0.002 ) , respectively . Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 ( 95 % CI , 0.770–0.877 ) and result ed in an net reclassification improvement of 41.4 % ( P continuous net reclassification improvement . Conclusion —Among multiple biomarkers from distinct biological pathways , E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke", "BACKGROUND Recent evidence supports the protective effects of n-3 ( omega-3 ) fatty acids ( n-3 FAs ) , such as eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) , on vascular function . OBJECTIVE We investigated the effects of EPA and DHA on postpr and ial vascular function in subjects with type 2 diabetes mellitus . DESIGN In a double-blind , placebo-controlled , r and omized , crossover manner , 34 subjects with type 2 diabetes mellitus received daily either 2 g purified EPA/DHA ( termed n-3 FAs ) or olive oil ( placebo ) for 6 wk . At the end of this period , we measured macrovascular ( brachial ultrasound of flow-mediated dilatation ; FMD ) and microvascular [ laser-Doppler measurements of reactive hyperemia ( RH ) of the h and ] function at fasting and 2 , 4 , and 6 h after a high-fat meal ( 600 kcal , 21 g protein , 41 g carbohydrates , 40 g fat ) . RESULTS Fasting vascular function remained unchanged after n-3 FAs and placebo . Postpr and ial FMD decreased from fasting after placebo , with a maximum decrease ( 38 % ) at 4 h-an effect that was significantly reduced ( P = 0.03 for time x treatment interaction ) by n-3 FA supplementation ( maximum decrease in FMD was at 4 h : 13 % ) . RH remained unchanged after placebo , whereas it improved significantly ( P = 0.04 for time x treatment interaction ) after n-3 FA supplementation ( maximum increase was at 2 h : 27 % ) . CONCLUSIONS In subjects with type 2 diabetes mellitus , 6 wk of supplementation with n-3 FAs reduced the postpr and ial decrease in macrovascular function relative to placebo . Moreover , n-3 FA supplementation improved postpr and ial microvascular function . These observations suggest a protective vascular effect of n-3 FAs", "OBJECTIVE Nuclear transcription factor kappaB ( NF-kappaB ) plays a key role in the inflammatory response and can be modulate by dietary fat . We have examined the effect of three diets , with different fat composition , on the activation of NF-kappaB on peripheral blood mononuclear cells ( P BMC s ) . METHODS Sixteen healthy men followed three 4-week diets , in a r and omised crossover design : a Western diet , rich in saturated fat ( SFA ) [ 22 % SFA , 12 % monounsaturated fat ( MUFA ) and 0 , 4 alpha-linolenic acid ] ; a Mediterranean diet [ alpha-linolenic acid ] , and a low fat diet enriched in alpha-linolenic acid [ NF-kappaB ( electrophoretic mobility shift assay ) in mononuclear cells and plasma concentrations ( ELISA ) of soluble vascular cellular adhesion molecule 1 ( VCAM-1 ) were examined after either diets . RESULTS Western diet increased 2.7-fold NF-kappaB compared with the Mediterranean diet ( p=0.038 ) and 1.79-fold with the alpha-linolenic acid diet ( p=0.07 ) . No differences were found between the last two . Furthermore , an increase on plasma VCAM-1 was observed with the Western diet ( p Mediterranean diet diminished NF-kappaB activation in mononuclear cells , compared with Western diet , supporting its cardioprotective properties . The effect of the n-3 enriched diet was intermediate", "Both ( n-3 ) long-chain PUFA ( LCPUFA ) and linoleic acid [ LA , 18:2(n-6 ) ] improve cardiovascular disease ( CVD ) risk factors , but a high-LA intake may weaken the effect of ( n-3 ) LCPUFA . In a controlled , double-blind , 2 x 2-factorial 8-wk intervention , we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile . Healthy men ( n = 64 ) were r and omized to 5 mL/d fish oil capsules ( FO ) [ mean intake 3.1 g/d ( n-3 ) LCPUFA ] or olive oil capsules ( control ) and to oils and spreads with either a high ( S/B ) or a low ( R/K ) LA content , result ing in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups . Diet , ( n-3 ) LCPUFA in peripheral blood mononuclear cells , blood pressure ( BP ) , heart rate ( HR ) , and plasma CVD risk markers were measured before and after the intervention . FO lowered fasting plasma triacylglycerol ( TAG ) ( P ial TAG measured after the intervention ( P monocyte chemoattractant protein-1 , neither the FO nor fat intervention affected fasting plasma cholesterol , glucose , insulin , fibrinogen , C-reactive protein , interleukin-6 , vascular cell adhesion molecule-1 , P-selectin , oxidized LDL , cluster of differentiation antigen 40 lig and ( CD40L ) , adiponectin , or fasting or postpr and ial BP or HR after adjustment for body weight changes . In conclusion , neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile in healthy men , but fish oil lowered plasma TAG in healthy subjects with initially low concentrations", "Objectives —To determine the effect of dietary supplementation with conjugated linoleic acid ( CLA ) on body mass index ( BMI ) , body fat distribution , endothelial function , and markers of cardiovascular risk . Methods and Results —Forty healthy volunteers with BMI > 27 kg/m2 were r and omized to receive a CLA isomeric mixture or olive oil in a 12-week double-blind study . Subcutaneous body fat and abdominal/hepatic fat content were assessed using skin-fold thicknesses and computed tomography scanning , respectively . Endothelial function was assessed by brachial artery flow-mediated dilatation ( FMD ) . Plasma isoprostanes were measured as an index of oxidative stress . CLA supplementation did not result in a significant change in BMI index or total body fat . There was a significant decrease in limb ( −7.8 mm , P but not torso skin-fold thicknesses or abdominal or liver fat content . Brachial artery FMD declined ( −1.3 % , P=0.013 ) , and plasma F2-isoprostanes increased ( + 91pg/mL , P=0.042 ) . Conclusions —A CLA isomeric mixture had at most modest effects on adiposity and worsened endothelial function . On the basis of these results , the use of the isomeric mixture of CLA as an aid to weight loss can not be recommended", "Background In type 2 diabetes , acute hyperglycemia worsens endothelial function and inflammation , while resistance to GLP-1 action occurs . All these phenomena seem to be related to the generation of oxidative stress . A Mediterranean diet , supplemented with olive oil , increases plasma antioxidant capacity , suggesting that its implementation can have a favorable effect on the aforementioned phenomena . In the present study , we test the hypothesis that a Mediterranean diet using olive oil can counteract the effects of acute hyperglycemia and can improve the resistance of the endothelium to GLP-1 action . Methods Two groups of type 2 diabetic patients , each consisting of twelve subjects , participated in a r and omized trial for three months , following a Mediterranean diet using olive oil or a control low-fat diet . Plasma antioxidant capacity , endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels were evaluated at baseline and at the end of the study . The effect of GLP-1 during a hyperglycemic clamp , was also studied at baseline and at the end of the study . Results Compared to the control diet , the Mediterranean diet increased plasma antioxidant capacity and improved basal endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . The Mediterranean diet also reduced the negative effects of acute hyperglycemia , induced by a hyperglycemic clamp , on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels . Furthermore , the Mediterranean diet improved the protective action of GLP-1 on endothelial function , nitrotyrosine , 8-iso-PGF2a , IL-6 and ICAM-1 levels , also increasing GLP-1-induced insulin secretion . Conclusions These data suggest that the Mediterranean diet , using olive oil , prevents the acute hyperglycemia effect on endothelial function , inflammation and oxidative stress , and improves the action of GLP-1 , which may have a favorable effect on the management of type 2 diabetes , particularly for the prevention of cardiovascular disease", "Inflammatory markers as circulating soluble cellular adhesion molecules ( sCAMs ) and high sensitive C-reactive protein ( hsCRP ) are elevated in patients with chronic heart failure ( CHF ) , and may constitute an increased risk of adverse outcome . Marine n-3 polyunsaturated fatty acids ( n-3 PUFA ) may have anti-inflammatory effect and reduce levels of sCAMs ( soluble intercellular adhesion molecule-1 ( sICAM-1 ) , vascular adhesion molecule-1 ( sVCAM-1 ) , P-selectin ) and hsCRP . In a r and omized , controlled trial , 138 patients with NYHA class II-III CHF were allocated to receive a daily supplement of 0.9 g of n-3 PUFA or olive oil for 24 weeks . After supplementation , no significant changes occurred in sCAMs or hsCRP after adjusting for possible confounders . However , a significant reduction was observed in sP-selectin in patients receiving n-3 PUFA , but this result was only of borderline significance in a between-group analysis . In conclusion , a daily supplement with 0.9 g of n-3 PUFA does not significantly affect plasma levels of sCAMs or hs-CRP in patients with CHF . n-3 PUFA may reduce sP-selectin , indicating a possible effect on platelet ( and endothelial ) activation . The results also indicate that the low dose of n-3 PUFA used in many intervention trials does not have deleterious effects on sCAMs or hsCRP", "OBJECTIVES We studied the effect of the Mediterranean diet on plasma levels of C-reactive protein ( CRP ) , white blood cell counts , interleukin (IL)-6 , tumor necrosis factor (TNF)-alpha , amyloid A , fibrinogen , and homocysteine . BACKGROUND To the best of our knowledge , the mechanism(s ) by which the Mediterranean diet reduces cardiovascular risk are not well understood . METHODS During the 2001 to 2002 period , we r and omly enrolled 1,514 men ( 18 to 87 years old ) and 1,528 women ( 18 to 89 years old ) from the Attica area of Greece ( of these , 5 % of men and 3 % of women were excluded because of a history of cardiovascular disease ) . Among several factors , adherence to the Mediterranean diet was assessed by a diet score that incorporated the inherent characteristics of this diet . Higher values of the score meant closer adherence to the Mediterranean diet . RESULTS Participants who were in the highest tertile of the diet score had , on average , 20 % lower CRP levels ( p = 0.015 ) , 17 % lower IL-6 levels ( p = 0.025 ) , 15 % lower homocysteine levels ( p = 0.031 ) , 14 % lower white blood cell counts ( p = 0.001 ) , and 6 % lower fibrinogen levels ( p = 0.025 ) , as compared with those in the lowest tertile . The findings remained significant even after various adjustments were made . Borderline associations were found regarding TNF-alpha ( p = 0.076 ) , amyloid A levels ( p = 0.19 ) , and diet score . CONCLUSIONS Adherence to the traditional Mediterranean diet was associated with a reduction in the concentrations of inflammation and coagulation markers . This may partly explain the beneficial actions of this diet on the cardiovascular system", "Obesity is associated with an increased risk of cardiovascular disease , whereas long-chain n-3 polyunsaturated fatty acids ( PUFAs ) from fish may have cardioprotective and anti-inflammatory effects . This study aim ed to investigate the hypothesis that acute and short-term supplementation with a low dose of marine n-3 PUFA exerts an anti-inflammatory effect in overweight subjects . In a double-blind , placebo-controlled trial with 2 parallel groups , 50 overweight subjects were r and omized to receive daily supplementation with 2 capsules containing either 2 g of fish oil ( 1.1 g marine n-3 PUFA ) or 2 g of olive oil . Blood sample s and adipose tissue biopsies were collected at baseline , after 1 day ( acute effect ) , and after 6 weeks ( short-term effect ) of supplementation . No significant effects were seen after supplementation for 1 day , but after 6 weeks , subjects receiving fish oil had a significant increase in the n-3 PUFA content of granulocytes and adipose tissue ( P were increased by 0.55 μg/mL ( 95 % confidence interval , 0.02 - 1.08 ) in the fish oil group compared with the control group ( P = .04 ) after 6 weeks of supplementation . Levels of interleukin 6 were inversely correlated to the marine n-3 PUFA content of granulocytes and adipose tissue at baseline ( excluding α-linolenic acid ) . In conclusion , daily supplementation with 1.1 g of marine n-3 PUFA significantly increased serum adiponectin , but the effect was small , and no overall anti-inflammatory effect of the supplement could be demonstrated", "BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants . Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels . RESULTS The long-term stability of C-reactive protein values ( within-person correlation coefficient , 0.59 ; 95 percent confidence interval , 0.52 to 0.66 ) was similar to that of both blood pressure and total serum cholesterol . After adjustment for base-line values for established risk factors , the odds ratio for coronary heart disease was 1.45 ( 95 percent confidence interval , 1.25 to 1.68 ) in a comparison of participants in the top third of the group with respect to base-line C-reactive protein values with those in the bottom third , and similar overall findings were observed in an up date d meta- analysis involving a total of 7068 patients with coronary heart disease . By comparison , the odds ratios in the Reykjavik Study for coronary heart disease were somewhat weaker for the erythrocyte sedimentation rate ( 1.30 ; 95 percent confidence interval , 1.13 to 1.51 ) and the von Willebr and factor concentration ( 1.11 ; 95 percent confidence interval , 0.97 to 1.27 ) but generally stronger for established risk factors , such as an increased total cholesterol concentration ( 2.35 ; 95 percent confidence interval , 2.03 to 2.74 ) and cigarette smoking ( 1.87 ; 95 percent confidence interval , 1.62 to 2.16 ) . CONCLUSIONS C-reactive protein is a relatively moderate predictor of coronary heart disease . Recommendations regarding its use in predicting the likelihood of coronary heart disease may need to be review ed", "OBJECTIVES The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity . BACKGROUND Endothelial-dependent vasodilatation is impaired during the postpr and ial state , and oxidative stress could play a key role in its development . METHODS Twenty-one hypercholesterolemic volunteers received two breakfasts , using a r and omized sequential crossover design . Both arms received the same olive oil , but one had its phenolic acid content reduced from 400 to 80 ppm . Ischemic reactive hyperemia ( IRH ) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake . Postpr and ial plasma concentrations of lipid fractions , lipoperoxides ( LPO ) , 8-epi prostagl and in-F(2alpha ) , and nitrates/nitrites ( NO(x ) ) were obtained at baseline and after 2 h of the fat meal . RESULTS The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function , as well as a greater increase in concentrations of NO(x ) ( p LPO ( p 8-epi prostagl and in-F2alpha ( p NO(x ) and enhanced endothelial function at the second hour ( r = 0.669 ; p IRH and LPO ( r = -0.203 ; p 8-epi prostagl and in-F2alpha levels ( r = -0.440 ; p high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postpr and ial state . This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites", "Traditional cardiovascular risk factors are associated with endothelial dysfunction . The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat . We propose to determine the chronic effect of three diets with different fat compositions on postpr and ial endothelial function and inflammatory biomarkers . Twenty healthy men followed three 4-week diets in a r and omised cross-over design : a Western diet , rich in saturated fat ( 22 % SFA , 12 % MUFA and 0.4 % alpha-linolenic acid ( ALA ) , all fractions are % of energy ) ; a Mediterranean diet , rich in MUFA ( , 24 % MUFA and 0.4 % ALA ) ; a low-fat diet enriched in ALA ( SFA , 12 % MUFA and 2 % ALA ) . At the end of each dietary period all subjects underwent a postpr and ial study . Plasma concentrations of lipid parameters , soluble intercellular cell-adhesion molecule-1 , soluble vascular cell-adhesion molecule-1 ( sVCAM-1 ) , nitrates and nitrites ( NOx ) and endothelial function studied by laser Doppler were examined at 0 , 2 , 4 , 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets ( P = 0.031 ) . The 4 h postpr and ial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet ( P = 0.043 ) . The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets ( P = 0.027 ) . We found no differences in the other parameters measured . Chronic ingestion of a Mediterranean diet avoids the postpr and ial deterioration of endothelial function associated with Westernised diets in healthy individuals", "Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions", "OBJECTIVES The goal of this study was to prospect ively examine the long-term predictive value of brachial-artery endothelial dysfunction for future cardiovascular events . BACKGROUND Brachial-artery endothelial function is impaired in individuals with atherosclerosis and coronary risk factors . The prospect i ve relation between endothelial function determined by brachial-artery ultrasound and long-term cardiovascular risk is unknown . METHODS We examined brachial-artery endothelial function using ultrasound in 199 patients with peripheral arterial disease before elective vascular surgery . Patients were prospect ively followed with an average follow-up of 1.2 years after surgery . RESULTS Thirty-five patients had an event during follow-up , including cardiac death ( 5 patients ) , myocardial infa rct ion ( 17 patients ) , unstable angina ( 10 patients ) , or stroke ( 3 patients ) . Preoperative endothelium-dependent flow-mediated dilation ( FMD ) was significantly lower in patients with an event ( 4.4 + /- 2.8 % ) compared with those without an event ( 7.0 + /- 4.9 % , p endothelium-independent vasodilation to nitroglycerin was similar in both groups . In a Cox proportional-hazards model , independent predictors of events included age ( p = 0.003 ) , more invasive surgery ( surgery other than carotid endarterectomy , p = 0.02 ) , and impaired brachial-artery endothelial function ( p = 0.002 ) . Risk was approximately nine-fold higher in patients with FMD long-term cardiovascular events in patients with peripheral arterial disease . The findings suggest that noninvasive assessment of endothelial function using brachial-artery FMD may serve as a surrogate end point for cardiovascular risk", "Objective : Conjugated linoleic acid ( CLA ) showed a wide range of beneficial biological effects with relevance for cardiovascular health in animal models and humans . Most human studies used olive oil as a reference . This study assessed the effect of CLA as compared with safflower oil on endothelial function and markers of cardiovascular risk in overweight and obese men . Heated safflower oil and olive oil were given for additional descriptive control . Methods : Eighty-five overweight men ( aged 45–68 years , body mass index 25–35 kg/m2 ) were r and omized to receive 4.5 g/d of the CLA isomeric mixture , safflower oil , heated safflower oil , or olive oil in a 4-week double-blind study . Endothelial function was assessed by peripheral arterial tonometry ( PAT ) index determination in the fasting and postpr and ial state ( i.e. , 4 hours after consumption of a fat- and sucrose-rich meal ) . Results : CLA as compared with safflower oil consumption did not impair fasting or postpr and ial PAT index but decreased body weight . CLA as compared with safflower oil did not change total , low-density lipoprotein ( LDL ) , or high-density lipoprotein ( HDL ) cholesterol ; triglycerides ; insulin sensitivity indices ; C-reactive protein ; soluble adhesion molecules ; oxidized LDL ; lipoprotein a ( Lp[a ] ) ; paraoxonase ; or platelet-activating factor acetylhydrolase ( PAF-AH ) activity , but significantly reduced arylesterase activity and increased concentrations of the F2-isoprostane 8-iso-prostagl and in F (PGF)2α . Conclusion : CLA did not impair endothelial function . Other parameters associated with metabolic syndrome and oxidative stress were not changed or were slightly improved . Results suggest that CLA does not increase cardiovascular risk . Increased F2-isoprostane concentrations in this context may not indicate increased oxidative stress", "BACKGROUND AND AIM Long-chain n-3 polyunsaturated fatty acids ( PUFA ) may protect against atherosclerotic disease , and serum levels of soluble cellular adhesion molecules ( sCAMs ) possibly reflect the inflammatory process underlying atherosclerosis . We studied the effect of n-3 PUFA dietary supplementation on the serum levels of sP-selectin , soluble intercellular adhesion molecule-1 ( sICAM-1 ) and soluble vascular adhesion molecule-1 ( sVCAM-1 ) , and the correlation between sCAMs and the fatty acid composition of granulocyte membranes . METHODS AND RESULTS Sixty healthy volunteers were r and omly assigned to receive a daily supplement of n-3 PUFA 6.6 g , n-3 PUFA 2.0 g , or olive oil for 12 weeks in a double blind design . A significant negative correlation was found between serum sICAM-1 levels and the DHA content of granulocyte membranes at entry . After supplementation with 6.6 g of n-3 PUFA , there was a significant decrease only in sP-selectin , which a gender sub analysis showed to be more marked in men . Among the women , there was a significant decrease in sICAM-1 in the PUFA 2.0 g group and a significant increase in sVCAM-1 in the PUFA 6.6 g group . CONCLUSIONS The results indicate that high-dose supplementation with n-3 PUFA decreases sP-selectin levels in healthy subjects , thus suggesting a decrease in platelet reactivity or endothelial activation . However , the effect of n-3 PUFA on sCAMs is complex and may depend on gender and n-3 PUFA dose", "OBJECTIVE Olive oil ( OO ) is a rich source of monounsaturated fat and bioactive components that exert strong anti-oxidant and anti-inflammatory properties . Flaxseed oil ( FO ) is rich in α-linolenic n-3 fatty acid ( ALA ) , which also exhibits anti-inflammatory effects . This r and omized , cross-over study aim ed at exploring whether diet 's enrichment with FO could beneficially alter inflammatory markers and lipid profile , compared to OO , in a sample of normal weight , apparently healthy young adults . MATERIAL S AND METHODS Participants were supplied with 15 mL/day of either FO or OO . Each intervention and the wash-out period lasted 6 weeks . Dietary , anthropometric and physical activity variables were recorded at the beginning and the end of each intervention . Serum biochemical and inflammatory markers were measured . Compliance to the intervention was evaluated by fatty acid analysis in erythrocytes . Repeated Measures ANOVA was used to assess the effect of the treatment . RESULTS Thirty seven participants completed the study . No difference between the two interventions was observed in adiponectin , TNF-α , high sensitivity-CRP or glucose levels and lipid profile . At the end of the FO period , participants exhibited significant reductions in total ( -5.0 % ) and LDL-cholesterol ( -6.7 % ) levels ( all P period serum adiponectin changes were significantly correlated with changes in erythrocyte % ALA ( rs=0.34 , P=0.007 ) and in erythrocyte % EPA ( r(s)=0.47 , P=0.01 ) , respectively . CONCLUSIONS Daily consumption of FO did not confer any benefit in inflammatory or biochemical markers in normal weight young adults , who traditionally use olive oil as the main edible oil", "BACKGROUND Dietary fat type is known to modulate the plasma lipid profile , but its effects on plasma homocysteine and inflammatory markers are unclear . OBJECTIVE We investigated the effects of high-protein Malaysian diets prepared with palm olein , coconut oil ( CO ) , or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease ( CVD ) in healthy adults . DESIGN A r and omized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects . The 3 test fats , namely palmitic acid (16:0)-rich palm olein ( PO ) , lauric and myristic acid ( 12:0 + 14:0)-rich CO , and oleic acid (18:1)-rich virgin olive oil ( OO ) , were incorporated at two-thirds of 30 % fat calories into high-protein Malaysian diets . RESULTS No significant differences were observed in the effects of the 3 diets on plasma total homocysteine ( tHcy ) and the inflammatory markers TNF-α , IL-1β , IL-6 , and IL-8 , high-sensitivity C-reactive protein , and interferon-γ . Diets prepared with PO and OO had comparable nonhypercholesterolemic effects ; the postpr and ial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower ( P decrease postpr and ial lipoprotein(a ) . CONCLUSION Diets that were rich in saturated fatty acids prepared with either PO or CO , and an OO diet that was high in oleic acid , did not alter postpr and ial or fasting plasma concentrations of tHcy and selected inflammatory markers . This trial was registered at clinical trials.gov as NCT00941837", "Purpose Recent epidemiological studies have shown that habitual consumption of extra virgin olive oil ( EVOO ) , the characteristic culinary fat of the Mediterranean area , is effective in the prevention of diverse types of digestive disorders such as inflammatory bowel disease . Many of these benefits are , in addition to its high proportion of oleic acid , due to the high content of phenolic compounds . Methods Six-week-old mice were r and omized into three dietary groups : st and ard , EVOO and hydroxytyrosol-enriched EVOO . After 30 days , mice that were exposed to 3 % DSS for 5 days developed acute colitis that progressed to severe chronic inflammation during a regime of 21 days of water . Results Diets enriched with EVOO significantly attenuated the clinical and histological signs of damage , improving results from disease activity index and reducing about 50 % the mortality caused by DSS . Moreover , hydroxytyrosol supplement showed better results . Cytokines study showed that TNF-α was maintained near to sham control and IL-10 levels were significantly improved in EVOO and EVOO plus hydroxytyrosol diet-DSS groups . In the same way , COX-2 and iNOS were downregulated , and the activation of p38 MAPK was reduced . We also observed a higher significant reduction in iNOS in hydroxytyrosol-enriched EVOO compared with EVOO alone . Conclusions EVOO diets exerted a noteworthy beneficial effect in chronic DSS-induced colitis by cytokine modulation and COX-2 and iNOS reduction via downregulation of p38 MAPK . In addition to the beneficial effect by EVOO , supplementation of the diet with hydroxytyrosol may improve chronic colitis through iNOS downregulation plus its antioxidant capacity", "The aim of the study was to assess whether benefits associated with the traditional Mediterranean diet ( TMD ) and virgin olive oil ( VOO ) consumption could be mediated through changes in the expression of atherosclerosis-related genes . A r and omized , parallel , controlled clinical trial in healthy volunteers ( n=90 ) aged 20 to 50 yr was performed . Three-month intervention groups were as follows : 1 ) TMD with VOO ( TMD+VOO ) , 2 ) TMD with washed virgin olive oil ( TMD+WOO ) , and 3 ) control with participants ' habitual diet . WOO was similar to VOO , but with a lower polyphenol content ( 55 vs. 328 mg/kg , respectively ) . TMD consumption decreased plasma oxidative and inflammatory status and the gene expression related with both inflammation [ INF-gamma ( INFgamma ) , Rho GTPase-activating protein15 ( ARHGAP15 ) , and interleukin-7 receptor ( IL7R ) ] and oxidative stress [ adrenergic beta(2)-receptor ( ADRB2 ) and polymerase ( DNA-directed ) kappa ( POLK ) ] in peripheral blood mononuclear cells . All effects , with the exception of the decrease in POLK expression , were particularly observed when VOO , rich in polyphenols , was present in the TMD dietary pattern . Our results indicate a significant role of olive oil polyphenols in the down-regulation of proatherogenic genes in the context of a TMD . In addition , the benefits associated with a TMD and olive oil polyphenol consumption on cardiovascular risk can be mediated through nutrigenomic effects", "BACKGROUND The dietary intake of n-3 ( omega-3 ) long-chain PUFAs ( LC-PUFAs ) from fish may improve endothelial function and arterial stiffness . OBJECTIVE The objective was to test the hypothesis that increasing intakes of n-3 LC-PUFAs-equivalent to the consumption of 1 , 2 , or 4 portions of oily fish per week-favorably affects endothelial function and arterial stiffness . DESIGN A parallel- design , r and omized , double-blind study compared daily doses of 0.45 , 0.9 , and 1.8 g n-3 LC-PUFAs ( EPA : DHA ratio of 1.51:1 ) with placebo ( refined olive oil ) . The primary and secondary outcomes were changes in flow-mediated dilatation ( FMD ) of the brachial artery , arterial stiffness , and blood pressure . Nonsmoking men ( n = 142 ) and women ( n = 225 ) aged 45 - 70 y were r and omly assigned to treatment for 12 mo ; 312 subjects completed the intervention . RESULTS Compliance with the intervention was corroborated by significant dose-dependent increases in the proportions of EPA and DHA in erythrocyte lipids and a 16.5 % reduction in serum triacylglycerol concentrations with 1.8 g n-3 LC-PUFAs/d . FMD was lower in men than in women ( P mean changes in FMD ( 95 % CIs ) compared with placebo were 0.1 % ( -0.9 % , 1.1 % ) , -0.3 % ( -1.3 % , 0.6 % ) , and -0.3 % ( -1.3 % , 0.7 % ) with daily intakes of 0.45 , 0.9 , and 1.8 g n-3 LC-PUFAs , respectively . No significant treatment effects were noted for arterial stiffness and central mean or 24-h ambulatory blood pressure . CONCLUSION Intakes of n-3 LC-PUFAs ≤1.8 g/d do not improve endothelial function in healthy adults . The trial is registered at controlled-trials.com as IS RCT N66664610", "Fish oil ( FO ) is considered antiinflammatory , but evidence regarding its effect on human cytokine production is conflicting . High linoleic acid ( LA ) intake may impair any effects of FO . The aim of this study was to investigate how FO combined with high or low LA intake affected ex vivo cytokine production from cultures of whole blood , peripheral blood mononuclear cells ( P BMC ) , and monocytes in healthy men . The study was a double-blinded , controlled , 2 x 2 factorial 8-wk intervention . Sixty-four healthy men were r and omized to 5 mL/d FO or olive oil ( OO ) provided in capsules and to spreads and oils with high or low LA content , result ing in LA intakes of 7 + /- 2 % and 4 + /- 1 % energy , respectively . We measured eicosapentaenoic acid ( EPA ) in P BMC and stimulated cytokine production in whole blood and P BMC 24-h cultures before and immediately after intervention and after an 8-wk wash-out period , and in monocyte cultures immediately after intervention . P BMC -EPA was markedly increased by FO ( P LA intake did not modify the incorporation of FO and tended to have only a slight effect on P BMC -EPA by itself ( P = 0.06 ) . Lipopolysaccharide (LPS)-stimulated whole-blood interleukin (IL)-6 production immediately after intervention was lower with FO than OO ( P = 0.02 ) but did not correlate with P BMC -EPA in the FO groups ( r = -0.12 ; P = 0.53 ; n = 31 ) . The LA intake did not modify IL-6 production or the effect of FO . Neither FO nor LA intake affected the production of tumor necrosis factor-alpha , IL-10 , or interferon-gamma in any of the cultures . In conclusion , FO intake reduced IL-6 production from LPS-stimulated whole blood in healthy men compared with OO , but the effect was not modified by the LA intake", "n-3 fatty acids reduce the risk of cardiovascular disease via a number of possible mechanisms . Despite this , there has been concern that these fatty acids may increase lipid peroxidation . The data in vivo are inconclusive , due in part to limitations in the method ologies . In this regard , the measurement of F2-isoprostanes provides a reliable assessment of in vivo lipid peroxidation and oxidant stress . This study aim ed to assess the effects of supplementation with purified eicosapentaenoic acid ( EPA ) or docosahexaenoic acid ( DHA ) , the two major n-3 fatty acids , on urinary F2-isoprostanes and markers of inflammation , in type 2 diabetic patients . In a double-blind , placebo controlled trial of parallel design , 59 nonsmoking , treated-hypertensive , type 2 diabetic subjects , were r and omized to 4 g daily of purified EPA , DHA , or olive oil for 6 weeks , while maintaining their usual diet . F2-isoprostanes , measured using gas chromatography-mass spectrometry in 24 h urines and C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha ( TNF-alpha ) , were measured before and after intervention . Thirty-nine men and 12 women aged 61.2 + /- 1.2 years , with body mass index ( BMI ) , 29.5 + /- 0.5 kg/m2 ; 24 h blood pressure , 138/73 mmHg ; HbA1c , 7.3 + /- 0.1 % and fasting glucose , 7.9 + /- 0.2 mmol/l completed the intervention . Baseline urinary F2-isoprostanes were positively associated with HbA1c ( p=.011 ) and fasting glucose ( p=.032 ) . Relative to the olive oil group , postintervention urinary F2-isoprostanes were decreased 19 % by EPA ( p=.017 ) and 20 % by DHA ( p=.014 ) . There were no significant changes in CRP , IL-6 , and TNF-alpha following EPA or DHA supplementation . In regression analysis , Delta F2-isoprostanes were positively associated with Delta HbA1c ( p=.007 ) independent of treatment group ; and with Delta TNF-alpha ( p=.034 ) independent of age , gender , BMI , and treatment group . There were no associations with Delta CRP or Delta IL-6 . This study is the first report demonstrating that either EPA or DHA reduce in vivo oxidant stress without changing markers of inflammation , in treated hypertensive , type 2 diabetic subjects", "BACKGROUND Olive oil polyphenols have been associated with several cardiovascular health benefits . This study aims to examine the influence of a polyphenol-rich olive oil on blood pressure ( BP ) and endothelial function in 24 young women with high-normal BP or stage 1 essential hypertension . METHODS We conducted a double-blind , r and omized , crossover dietary-intervention study . After a run-in period of 4 months ( baseline values ) , two diets were used , one with polyphenol-rich olive oil ( ∼30 mg/day ) , the other with polyphenol-free olive oil . Each dietary period lasted 2 months with a 4-week washout between diets . Systolic and diastolic BP , serum or plasma biomarkers of endothelial function , oxidative stress , and inflammation , and ischemia-induced hyperemia in the forearm were measured . RESULTS When compared to baseline values , only the polyphenol-rich olive oil diet led to a significant ( P mm Hg in systolic and 6.65 mm Hg of diastolic BP . A similar finding was found for serum asymmetric dimethylarginine ( ADMA ) ( -0.09 ± 0.01 µmol/l , P 0.01 ) , oxidized low-density lipoprotein ( ox-LDL ) ( -28.2 ± 28.5 µg/l , P ) , and plasma C-reactive protein ( CRP ) ( -1.9 ± 1.3 mg/l , P The polyphenol-rich olive oil diet also elicited an increase in plasma nitrites/nitrates ( + 4.7 ± 6.6 µmol/l , P containing polyphenol-rich olive oil can decrease BP and improve endothelial function in young women with high-normal BP or stage 1 essential hypertension", "BACKGROUND Traditional diets that include moderate to high intakes of extra virgin olive oil have been related to a decrease in breast cancer risk . We hypothesized that an olive oil-enriched diet would lead to greater weight loss and acceptance , compared with a st and ard diet , in women previously diagnosed with invasive breast cancer . METHODS Participants consumed a National Cancer Institute ( NCI ) diet ( total fat > 15 % and and a plant-based olive oil diet ( PBOO ; > or = 3 tablespoons of olive oil/day ) for 8 weeks , each with r and om assignment to the order . We established a weight loss goal of at least 5 % of baseline weight . After completion of the two diet trials , each participant self-selected one of the diets for an additional 6 months of follow-up for weight management . Body measures were done before and after each diet and after follow-up ; fasting blood sample s were collected after each diet and after follow-up . RESULTS Forty-four overweight women started and 28 completed the 44-week protocol . Twelve ( 80 % ) of the 15 women who started with the PBOO diet achieved a weight loss of > or = 5 % compared to 4 ( 31 % ) of the 13 who started with the NCI diet ( p 22 women eligible for follow-up chose the PBOO diet , and all completed the study . Of the 3 women who chose the NCI diet for follow-up , 1 completed the study . The PBOO diet result ed in lower triglycerides ( NCI 105 + /- 46 mg/dL , PBOO 96 + /- 37 mg/dL , p = 0.06 ) and higher high-density lipoprotein cholesterol ( HDL-C ) ( NCI 64 + /- 13 mg/dL , PBOO 68 + /- 12 mg/dL , p = 0.001 ) . CONCLUSIONS An olive oil-enriched diet brought about greater weight loss than a lower-fat diet in an 8-week comparison . Moreover , these women chose , overwhelmingly , the olive oil-enriched diet for 6 months of follow-up . An olive oil-enriched diet may be more efficacious for weight loss in breast cancer survivors than a st and ard lower-fat diet", "Anta rct ic krill , also known as Euphausia superba , is a marine crustacean rich in both eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) . We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety , tolerability , or selected metabolic parameters . In this r and omized , double-blind parallel arm trial , overweight and obese men and women ( N = 76 ) were r and omly assigned to receive double-blind capsules containing 2 g/d of krill oil , menhaden oil , or control ( olive ) oil for 4 weeks . Results showed that plasma EPA and DHA concentrations increased significantly more ( P Systolic blood pressure declined significantly more ( P Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group ( P adverse events . In conclusion , 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated , with no indication of adverse effects on safety parameters", "Adherence to a Mediterranean diet ( MD ) is associated with a reduced risk of coronary heart disease . However , the molecular mechanisms involved are not fully understood . The aim of this study was to compare the effects of 2 MD with those of a low-fat-diet ( LFD ) on circulating inflammatory biomarkers related to atherogenesis . A total of 516 participants included in the Prevention with Mediterranean Diet Study were r and omized into 3 intervention groups [ MD supplemented with virgin olive oil ( MD-VOO ) ; MD supplemented with mixed nuts ( MD-Nuts ) ; and LFD ] . At baseline and after 1 y , participants completed FFQ and adherence to MD question naires , and plasma concentrations of inflammatory markers including intercellular adhesion molecule-1(ICAM-1 ) , IL-6 , and 2 TNF receptors ( TNFR60 and TNFR80 ) were measured by ELISA . At 1 y , the MD groups had lower plasma concentrations of IL-6 , TNFR60 , and TNFR80 ( P ICAM-1 , TNFR60 , and TNFR80 concentrations increased in the LFD group ( P lower plasma concentrations of ICAM-1 , IL-6 , TNFR60 , and TNFR80 compared to those in the LFD group ( P ≤ 0.028 ) . When participants were categorized in tertiles of 1-y changes in the consumption of selected foods , those in the highest tertile of virgin olive oil ( VOO ) and vegetable consumption had a lower plasma TNFR60 concentration compared with those in tertile 1 ( P the geometric mean TNFR60 concentrations were those of VOO and vegetables ( P = 0.01 ) . This study suggests that a MD reduces TNFR concentrations in patients at high cardiovascular risk" ]	41186f8a-06ff-11f0-808a-c43d1ab1c353

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